Cancer Prevention Research Research Articles

Abstract B19: Malfunction and mutation of airway stem/progenitor cells in preneoplastic bronchial dysplasia

Abstract Squamous cell lung cancer (SCC) is the second leading cause of lung cancer death in the US with a 5-year survival rate of 16.8%. Since most SCC is diagnosed at a late stage, chemoprevention or early detection could improve survival. SCC develops through a series of histological alterations including dysplasia and carcinoma in situ. Previous studies have identified genetic changes in epithelial progenitor cells in dysplastic lesions. The goal of this project is to establish a correlation between specific genetic changes in epithelial progenitors and their function. A tissue stem cell is a progenitor cell that is capable of long-term self-renewal as well as differentiation to all the cell-types that make up a specific tissue and therefore is multipotential. Because the normal function of a progenitor cell is to repair and regenerate a native epithelium after injury, histologic changes in dysplasia led us hypothesize that “normal function of airway progenitors is altered in dysplasia”. To address this hypothesis we purified and established clonal cultures of basal progenitors from normal, moderate and severely dysplastic biopsies and compared their self-renewal and differentiation abilities. These analyses revealed that the self-renewal capacity of progenitor cells decreased as dysplasia grade increased. The progenitors from normal biopsies differentiated to all three cell-types (basal, secretory or mucin-secreting and ciliated) of the airways. In contrast, progenitors from dysplasia generated increased numbers of basal cells (p<0.05) and lacked secretory (p<0.001) and ciliated cells (p<0.001), suggesting that multipotential differentiation is impaired in dysplasia. Genetic analyses of dysplastic lesions and cultured dysplastic progenitors (n=4, histology grade ≥ 5.5) identified several mutations (p53, Notch 1, 2 and 3, FBXW7, and FGFR1) that have been previously reported in SCC. Thus, we demonstrate that we are able to culture airway stem/progenitor cells that recapitulate both the phenotypic and mutational characteristics of the lesions from which they originate. We propose that understanding the effect of these mutations in altered progenitor function will help to devise prevention as well as early detection strategies. Citation Format: Moumit Ghosh, Ichiro Nakachi, Robert L. Keith, Daniel T. Merrick, Wilbur A. Franklin, York E. Miller. Malfunction and mutation of airway stem/progenitor cells in preneoplastic bronchial dysplasia. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B19.

Abstract B10: Fasting blood glucose and bone mineral density in Latina breast cancer survivors

Abstract Background. Elevated fasting blood glucose (FBG) in Latina women has been identified as a risk factor for osteoporosis, independent of history of breast cancer. Elevated FBG, a sign of poor glycemic control among Latina women has been shown to increase bone resorption and subsequent bone loss over time. Treatment for breast cancer can also result in significant decreases in bone mineral density (BMD), which may be further exacerbated by the premature onset of menopause. Decreases in estrogen associated with the onset of menopause and hormonal therapy have been shown to accelerate bone loss in women. Purpose. The purpose of the present investigation was: 1) to examine the association between FBG and lumbar spine and hip (regional) BMD in Latina breast cancer survivors (LBCS); and 2) to examine the influence of menopausal status on FBG and BMD in LBCS. We hypothesized that increased FBG would be correlated with decreased lumbar spine and hip BMD in LBCS. Additionally, it was hypothesized that postmenopausal status would further exaggerate the association between increased FBG and BMD in LBCS. Methods. The present study included baseline data from 24 LBCS, recruited from Los Angeles County Hospital and Norris Comprehensive Cancer Center at USC as a part of a larger ongoing exercise trial. Participants included Stage I-III breast cancer patients who were sedentary and had received chemotherapy and/or radiation within 6 months prior to joining the study. Participants reported to the Women's Health and Exercise Laboratory at the USC for data collection. Participants were required to fast for 12 hours prior to the study visit and plasma FBG was measured using a venous sample from the antecubital vein. Participants completed a dual-energy x-ray absorptiometry (Lunar DEXA®GE Healthcare) scan to measure right (R) and left (L) hip (femur; F) BMD (RFBMD, LFBMD, respectively) and lumbar spine BMD (LSBMD). T scores were obtained via DEXA scan, which is the score of the site-specific BMD when compared to the young (30-year-old woman) normal reference mean. Pearson correlations were used to examine associations between FBG and T-scores of RF/LF/LS BMD in LBCS. Independent t-tests were used to compare mean FBG and BMD values between premenopausal and postmenopausal LBCS. Statistical significance was set at p<0.05. Results. Mean ages were 46.2±7.0 years in premenopausal (PRE) LBCS (n=10) and 56.9±7.5 years in postmenopausal (POST) LBCS (n=14). Mean FBG and T-scores of regional BMD (LSBMD, RFBMD, LFBMD) are listed in Table 1. Mean FBG was significantly greater in postmenopausal LBCS when compared to premenopausal women (p<0.01). T-scores of LSBMD, RFBMD and LFBMD did not significantly differ in premenopausal and postmenopausal LBCS (p=0.58, p=0.97, p=0.54, respectively). Increased FBG was not associated with decreased LSBMD, RFBMD or LFBMD in premenopausal LBCS (p=0.38, r2=-0.31; p=0.99, r2=0.01; p=0.75, r2=0.12, respectively). Increased FBG was not associated with decreased LSBMD, RFBMD or LFBMD in postmenopausal LBCS (p=0.16, r2=0.40; p=0.80, r2=0.08; p=0.55, r2=0.17, respectively). Conclusion. In this limited sample size, FBG was not shown to be a predictive factor for decreased BMD in either premenopausal or postmenopausal LBCS, despite elevated FBG in postmenopausal LBCS. Our results differed from our hypothesis which, may be due to FBG levels that were only slightly elevated in LBCS with relatively healthy BMD. However, future investigations are warranted to further investigate whether elevated FBG is a risk factor for osteoporosis in larger sample of LBCS over a longer follow-up period. Table 1. Outcome Measures PRE LBCS FBG** 95.0±6.72 mg/dL* LSBMD T-score# -0.32±0.73 RFBMD T-score# 0.33±0.34 LFBMD T-score# 0.14±0.35 POST LBCS FBG** 107.8±22.0 mg/dL* LSBMD T-score# -0.14±0.054 RFBMD T-score# 0.25±0.42 LFBMD T-score# 0.27±0.34 **Means are ± SD; #Means are ± SE. *Means are statistically significantly different (p<0.05). Citation Format: Christina Dieli-Conwright, Lindsey Avery, Joanne Mortimer, Debu Tripathy, Darcy Spicer, Leslie Bernstein. Fasting blood glucose and bone mineral density in Latina breast cancer survivors. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B10.

Abstract B33: Regulation and function of Nrf2-associated long noncoding RNA

Abstract We hypothesized that the long non coding RNA (lncRNA), Loc344887, is induced by Nrf2 activation and acts as a transcriptional co-activator of the Nrf2 target gene NQO1. Nrf2 is a transcription factor that is important in oxidative stress responses. Upon oxidative stress, Nrf2 is released from its binding partner Keap1. Nrf2 translocates to the nucleus, partners with small Maf proteins, binds to antioxidant response elements (ARE) and induces detoxifying and metabolizing genes such as NQO1, HMOX1, and GSTs. We propose that Loc344887 is acting as a co-activator of Nrf2, either directly in the Nrf2-Maf complex, or indirectly by some other downstream mechanism, in order to regulate NQO1 expression. Loc344887 has significantly reduced expression in human colon tumors when compared to normal colon tissue (TCGA database). Human HCT116 colon cancer cells and CCD841 non-cancer colonic epithelial cells replicate this expression difference between tumor and non-transformed. We used these cell lines to study the regulation and function of Loc344887. HCT116 and CCD841 cells were treated with 15 μM sulforaphane (SFN), a dietary isothiocyanate known to have chemopreventative properties due to Nrf2 activation. Loc344887 increased 40-fold in HCT116 cells, but was not induced in CCD841 cells. Loc344887 was also induced by oltipraz and tert-butylhydroquinone, known Nrf2 activators. Keap1 knockdown upregulated Loc344887, and inducibility of Loc344887 by SFN was lost when Nrf2 was knocked down using RNAi. The gene promoter of Loc344887 contains putative AREs, and chromatin immunoprecipitation assays identified putative Nrf2 and MafK binding regions. Because Loc344887 is regulated by Nrf2, we hypothesized that Loc344887 may be involved in NRF2 gene activation. Knockdown of Loc344887 caused a loss of NQO1 induction by both SFN and Keap1 knockdown; however, this effect was not seen for HMOX1. Time-course assays showed that Loc344887 is induced as early as 1 h post-SFN treatment and peaks at ~8 h, similar to HMOX1. NQO1, however, was induced much slower, peaking after 24 h. This suggests that other factor(s), such as Loc344887, needs to be present for full induction to occur. This study shows that Loc344887 is an Nrf2 target gene and is required for complete NQO1 induction, but not for HMOX1 activation. Thus, there is a differential response for Nrf2 target genes that depends, in part, on lincRNAs as co-regulators. Further studies are required to access the mechanism of NQO1 regulation. We hypothesize that once Loc344887 is induced, it acts as a scaffold for MafK, Nrf2 and/or other transcription factors on the NQO1 promoter. Loc344887 localizes primarily to the nucleus, and preliminary RNA immunoprecipitation experiments show that Loc344887 binds directly to MafK. Further studies will also test whether Loc344887 is required for regulation of other Nrf2 target genes, or if other lncRNAs are involved in Nrf2 target gene induction. Studies supported in part by Chancellor's Research Initiative funding from Texas A&M University, and by NIH grants CA090890, CA122959, P30 ES00210, P30 ES023512. Citation Format: Gavin Johnson, Laura Beaver, David E. Williams, Emily Ho, Roderick H. Dashwood. Regulation and function of Nrf2-associated long noncoding RNA. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B33.

Abstract A54: Possible targets of metformin in colorectal cancer

Abstract Background: Growing evidence suggests metformin improves survival in diabetic colorectal cancer (CRC) patients. However, the mechanism of action remains unclear. In order to explore the mechanistic relationship between metformin and colon cancer, we examined the expression levels of several proteins implicated in metformin's action. Methods: We collected clinical-pathological and outcomes data on all CRC patients treated at the University of Chicago (UC) from 2006-2010. The data was collected through UC cancer registry and chart review. Diabetic CRC patients and matched controls (matched on race and stage) were selected for immunostaining (IHC). Tissues blocks (FFPE) were retrieved and tissue microarray (TMA) were constructed. IHC was performed for pAMPK, pmTOR, p70S6K, 4E-BP1, pAKT, IGF1R, beta-Catenin and Ki-67. Total score was calculated from the intensity and percentage scoring. The results were analyzed in two groups: diabetic CRC patients on metformin (group 1) and diabetic or non-diabetic CRC patients not on metformin (group 2). Chi-square test was done for estimating statistical significance between groups keeping a level of significance at 10% (alpha < 0.10). Results: The mean age of CRC patients was 62.7 years, 49% were males. Out of a total of 700 patients, 79 (11.21%) were diabetic. Metformin was prescribed to 40.5% of diabetic patients. Only 52 diabetics have FFPE block available so TMA was constructed with 104 patients in total (52 cases and 52 controls). Immunostaining was analyzable for a total of 84 patients. There were 18 and 66 patients in group 1 and 2, respectively. We found a lower expression of Ki-67 in the metformin group (group 1; 39%) as compared to non-metformin group (group 2; 64%) which was statistically significant (p = 0.04). IGF1R and beta-Catenin showed a higher expression in non-metformin group (89% and 95%, respectively) as compared to metformin group (72% and 83%, respectively) which was close to significance (p=0.12 and p=0.13, respectively). There was no significant difference between the expression of pAMPK, pmTOR, p70S6K, 4E-BP1 and pAKT in the two groups. Conclusions: Metformin appears to improve the survival of CRC patients by decreasing proliferation. The results need to be validated in a larger study. Citation Format: Amikar Sehdev, Galina Khramtsova, Nora Joseph, Blase P. Polite, Marc B. Bissonnette, Olopade I. Olufunmilayo. Possible targets of metformin in colorectal cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A54.

Abstract B46: The influence of exemestane on breast density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial

Abstract Background: Endogenous estradiol blood levels and high breast density are both associated with an increased risk for breast cancer (BC), but, there is conflicting evidence about whether or not they influence breast cancer risk through a shared pathway. Exemestane is an aromatase inhibitor that blocks the synthesis of estrogen and has been demonstrated to reduce the incidence of breast cancer in postmenopausal women by 65%. However the effects of exemestane on breast density remain unclear. Objectives: The primary objective of this research was to prospectively examine the relationship between exemestane versus placebo and changes in mammographic breast density (BD) in postmenopausal women during 3 or more years of treatment. Methods: The NCIC Clinical Trials Group conducted a phase III randomized controlled trial (RCT) comparing exemestane (E), with placebo (P) in postmenopausal women at higher than average risk for BC (MAP.3). This study was nested within the MAP.3 RCT using data from 568 participants across Canada and Buffalo, New York. Information on treatment allocation and established risk factors for BC was previously collected and data on the outcome measures was obtained from mammograms. Baseline and follow-up mammograms were collected from participating centres and were measured (percent density) using Cumulus software by our team radiologist (DJ). Multivariable linear regression was used to estimate the effect of exemestane treatment on >=3 year change in percent BD from randomization controlling for potential confounding variables. Results: Percent BD was measured for 386 participants (E=200, P=186) with a baseline and >=3 year follow-up mammogram that was matching in format (i.e. film or digital). The average age of women at study entry was 63 years and the average Gail score was 2.8%. The mean BD was similar in both arms at baseline (P: 12.9% (SD: 14.5) and E: 13.7% (SD: 14.4)). Similarly, the annual mean change in percent BD was not significantly different between the two treatment arms (P: 0.63% (SD: 1.82) vs E: .077% (SD: 1.80); p=0.90). After controlling for potential confounders (age, body mass index, first degree family history of BC and prior use of HRT), exemestane was not predictive of change in percent BD (p-value=0.641). Neither age (<60 vs. >=60 yrs) nor BMI modified the exemestane-breast density relationship significantly. Conclusion: We found no association between >=3 years of exemestane use and change in percent BD among a subset of postmenopausal women participating in MAP.3. These results suggest that estrogen and breast density may have independent pathways in breast cancer etiology. Citation Format: Harriet Richardson, Paul E. Goss, Melanie Walker, Doris Jabs, Will King. The influence of exemestane on breast density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B46.

Abstract B13: Knowledge, attitude and practice of cervical cancer preventive strategies among market women in Ibadan, Nigeria

Abstract Cervical cancer is the fourth most common cancer worldwide for females and the seventh most common cancer overall. Nigeria, a developing country, ranked tenth globally and fifth in Africa, has a mortality rate of 22.9 deaths per 100,000 with 14,000 new cases being diagnosed annually. In an effort to reduce this mortality rate, this research was undertaken to assess the level of awareness, attitude and practice of common cancer preventive strategies such as screening and the treatment of precancerous lesions using LEEP as a case study among women. A descriptive design using simple random sampling methods with self-administered questionnaires or interview methods (for illiterates) were used to collect data from the sample population. Market women were used (4 major markets in Ibadan) because they provided a sample population of women both in their reproductive and menopausal groups, with various level of literacy. Data was analyzed using the SPSS version 15. Of the total 100 respondents, only 55% had heard about cervical cancer while just 35% had heard about cervical screening test. 26% cited schools while 16% of the 35% cited mass media as their sources of awareness about the disease. 96% agreed that it was important to be screened for early diagnosis, 90% of all acknowledged the importance of this screening test in reducing deaths from cervical cancer. However, only 4% had ever been screened in their lifetime. Despite this, 74% of total respondents had a positive attitude to being screened while an additional 16% would have loved to be screened if the test was made free. On the role of treatment of precancerous lesions as a means of reducing mortality rate, 26% were aware about the Loop Electrosurgical Excision Procedure (LEEP) while only 40% of that agreed that it was curative. 84% agreed that women should be aware about the procedure, 85% agreed that it could reduce maternal mortality rates from cervical cancer. 92% suggested that the government should increase public campaign about preventing the disease, 79% encouraged more community awareness and availability of preventive strategies at the primary health centers while 87% promised to pass the information they had to other women. 93% noted that more women will seek early medical care if the LEEP was made free. 30% expressed poor knowledge among physicians due to their not being appropriately counseled and 84% expressed the need for further training among clinicians. Despite limitations in funding, it is suggested that more research work can be done to assess possible ethical beliefs towards contraceptives, HPV vaccine and sexual practices and how they affect cervical cancer incidence and mortality rates. Note: This abstract was withdrawn after the Proceedings were printed and, therefore, was not presented at the conference. Citation Format: Olohirere Tomisin Ezomo. Knowledge, attitude and practice of cervical cancer preventive strategies among market women in Ibadan, Nigeria. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B13.

Abstract PL02-02: Tomatoes, lycopene, and prostate cancer

Abstract In 1995, the first large prospective cohort data emerged from the Health Professionals Follow-up Study (HPFS) demonstrating a protective association between the intake of tomatoes and processed tomato products and a lower risk of prostate cancer (PCa). By utilizing data-bases of food content of carotenoids it has been possible to demonstrate similar associations between the estimated intake of lycopene (LYC), the non-provitamin A carotenoid providing the familiar red color of tomatoes, and PCa risk. With an additional two decades of monitoring the associations originally identified in the HPFS remain consistent in the 2014 update, while other epidemiologic studies are less convincing. LYC and other carotenoids were documented in human prostate tissue supporting the hypothesis of a direct effect on prostate carcinogenesis. Studies employing various laboratory models from multiple investigators show that tomato components or pure LYC have a protective impact on experimental prostate carcinogenesis. Although an antioxidant mechanism is frequently imputed based upon the known capacity of LYC to quench reactive oxygen species, other potential mechanisms of action related to hormonal activity, cell signaling and growth control, angiogenesis, and metastasis have emerged. Yet, proof of a protective relationship remains elusive and there are many obstacles to defining the impact of specific plant derived phytochemicals for human prostate cancer risk. The importance of dose-response, host genetics, and the complexity of human prostate cancer are but a few of the challenges faced in establishing a causal relationship. The examination of a tomato, lycopene, and prostate cancer relationship provides an example for considering how we as a discipline will address the challenges of defining food or phytochemical based interventions for cancer risk. Citation Format: Steven K. Clinton. Tomatoes, lycopene, and prostate cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL02-02.

Abstract B11: An efficient resource to accelerate research into the cause and prevention of breast cancer: The Army of Women

Abstract Background: It is well established that more research into the cause and prevention of breast cancer is needed. While studies are done in cell lines and lab animals, translation of findings to women is often delayed due to difficulty in recruitment. To address this problem, the Dr. Susan Love Research Foundation formed the Army of Women® (AOW); an online recruitment resource designed to partner women with researchers in order to accelerate breast cancer research. Methods: Researchers submit a proposal to the Dr. Susan Love Research Foundation's Scientific Advisory Committee. If a study is accepted, a mass e-mail describing the study procedures and inclusion/exclusion criteria is sent to the entire AOW database. Women sign up at www.armyofwomen.org to join and receive AOW e-mails about breast cancer research studies. Women self-select based on interest and study criteria, and undergo a secondary online screening before contact information is passed on to the researcher for the enrollment process. Results: Over 376,000 women have signed up, including survivors and women without a history of breast cancer, ranging from ages 18 to 100, representing all 50 US states and 49 countries. To date, the AOW has recruited for 87 studies. The diversity of the AOW members has proved beneficial for many studies, such as those needing to enroll racial/ethnic minorities, women of varying sexual orientations, or young survivors. A secondary goal of the AOW is to assist researchers new to research with human subjects. The AOW has successfully helped researchers cross the chasm, coaching them on what it takes to transition their research from animal models to human subjects. Conclusions: The AOW has proved to be a successful resource for scientists to accelerate accrual, expand the number and diversity of their subject population and to obtain exactly the type of specimens they need when they need it. This partnership between women and scientists has revolutionized research and accelerated efforts to eradicate breast cancer. The public is ready and willing to partner with the research community to find the answers to urgent clinical problems. Citation Format: Susan M. Love, Leah D. Eshraghi. An efficient resource to accelerate research into the cause and prevention of breast cancer: The Army of Women. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B11.

Abstract A05: Menopausal vasomotor symptoms and mammographic density in the Study of Women's Health Across the Nation

Abstract Background: Declines in endogenous estrogen during menopause have been linked to the onset of menopausal vasomotor symptoms (VMS) and to reduced breast cancer risk. Percent mammographic density (PMD) is viewed as a marker for breast cancer susceptibility. Establishing a relationship between VMS and PMD may justify future prospective investigations of VMS and breast cancer risk. Methods: We investigated this association in the Study of Women's Health Across the Nation (SWAN) Mammgraphic Density Substudy (N=833). Women were pre- or perimenopausal at enrollment and followed through menopause. VMS were assessed at annual SWAN visits. PMD was ascertained from routine screening mammograms. A linear mixed effects model was used to evaluate the longitudinal association between VMS and PMD. Results: Women contributed a total of 4,748 mammograms (2-10 per woman) over a median 5.4 years. We observed no overall association between VMS and PMD. When stratified by menopausal status, VMS was associated with lower PMD among perimenopausal women (β = -1.29%, 95%CI -2.58, -0.001) and those with unknown menopausal status due to hormone use during the study period (β = -3.62%, 95%CI -7.17, -0.07). VMS was not associated with absolute dense area in any analyses. Among women who transitioned to postmenopausal, VMS was not associated with change in PMD across the menopausal transition. Conclusion: Although our findings do not suggest a strong association between VMS and PMD, we observed a significant effect among perimenopausal women and those using hormones during menopause.. Further prospective studies are needed to establish a relationship between VMS and breast cancer risk, and to ascertain the extent to which this relationship may be mediated by PMD. Citation Format: Vicki Hart, Susan Sturgeon, Nicholas Reich, Lynnette Leidy Sievert, Sybil Crawford, Ellen Gold, Laurel Habel, Katherine W. Reeves. Menopausal vasomotor symptoms and mammographic density in the Study of Women's Health Across the Nation. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A05.

Abstract CN01-01: Big challenges of big data: Biomedical science in the petabyte era

Abstract Next-generation sequencing technologies (NGS) have exploded in popularity in recent years thanks to their ability to produce an enormous volume of data quickly and at relatively low cost compared to traditional sequencing methods such as Sanger sequencing. The emergence of NGS has pushed forward the goal of personalized medicine, but looking at the entire scope of a study from experimental design to data analysis to the ultimate goal of dose selection based on a patient's genome reveals many more challenges. Sample size for RNA-seq studies has been a persistent problem that has only recently received attention. Sequencing data analysis packages are numerous and constantly in development, but without a clear gold standard, they can be more overwhelming than helpful. Finally, this genomic information must be seamlessly integrated with clinical information for the knowledge to be useable by practitioners before the goal of personalized medicine can become a reality. Citation Format: Yu Shyr. Big challenges of big data: Biomedical science in the petabyte era. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN01-01.

Abstract PR07: Calorie restriction normalizes global microRNA expression by preventing the loss of Dicer expression during mammary tumorigenesis

Abstract MicroRNA (miRNAs) are small, post-transcriptional regulators that play an integral role in maintenance of cellular functions and whose dyregulation has been shown to promote many types of cancer, including breast cancer. Global downregulation of miRNAs has emerged as a common theme in human breast tumors and has been shown to contribute to oncogenesis. One of the primary mechanisms through which miRNAs are globally dysregulated is downregulation of enzymes involved in miRNA biogenesis. We aim to establish how calorie restriction (CR), which potently inhibits breast cancer progression, regulates global miRNA expression and miRNA biogenesis enzyme functionality in mammary tumors. To address these questions, 100 female Sprague Dawley rats were administered either dimethylbenz(a)anthracene (DMBA) or vehicle control at 50 days of age, then randomized to receive either control (AIN-76A) diet ad-libitum (n=40) or a 30% CR diet regiment (n=60). Resultant mammary tumors were allowed to develop for 12 weeks. Calorie restriction significantly increased survival to study endpoint relative to control diet (75% vs 35%, respectively) (p=0.0047). Furthermore, of the animals that developed tumors, CR significantly decreased median tumor area by 56% compared to control diet (109.4 mm2 vs 250.9 mm2, respectively) (p=0.0286). Global miRNA expression was analyzed through miRNA-specific sequencing. Calorie restriction had a broad effect on miRNA expression, illustrated by the fact that of all the miRNAs with a greater than two-fold expression difference between CR and control, 80% are overexpressed in CR tumors compared to control tumors. These results can be explained by the additional finding that CR was able to prevent the loss of Dicer expression, a key miRNA biogenesis enzyme, observed in control-fed mammary tumor tissue compared to normal tissue. This important finding suggests that global miRNA normalization through the retention of Dicer expression during cancer progression could be a contributing mechanism to CR's anticancer effects. We plan to further these investigations by exogenously manipulating Dicer expression in Rama25 cells, which were originally derived from a DMBA-induced mammary tumor from a Sprague Dawley rat, and analyzing the resultant tumorigenic potential in vitro and in vivo. The results obtained will provide insights into the mechanisms of breast cancer progression and how CR inhibits progression through microRNA modulation. Citation Format: Kaylyn L. Devlin, Tiffany Sanford, Elizabeth Mambo, Stephen D. Hursting. Calorie restriction normalizes global microRNA expression by preventing the loss of Dicer expression during mammary tumorigenesis. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR07.

Abstract PL04-01: Metabolic approaches to cancer prevention

Abstract It is well known that macronutrient intake and exercise influence cancer risk (1). They also have important metabolic effects because they determine energy balance at the whole organism level. There is accumulating evidence that the association between obesity and cancer risk may be attributable to the endocrine-metabolic consequences of chronic positive energy balance. Examples of candidate mediators of the effect of excess energy intake on risk of cancer are increased insulin levels and decreased adiponectin levels (2,3). Mechanistically, by increasing PI3K pathway activation (due to hyperinsulinemia) or decreasing AMPK activation (due to decreased adiponectin (4)) in various renewing epithelial cell populations at risk for transformation, these hormonal changes favor cell survival and proliferation over apoptosis. This increases the probability of survival of a clone bearing an oncogenic mutation, which in turn increases risk of subsequent ‘hits’ leading to full transformation. Recent population studies demonstrating these associations will be reviewed. Importantly, the effect of energy balance on cancer risk varies substantially with cancer type: for example, obesity is strongly associated with endometrial but not lung cancer, consistent with the view that optimizing metabolic risk factors may be insufficient to reduce cancer incidence in settings where carcinogen exposure is high. Furthermore, unexpected interactions between metabolic risk factors and prevention strategies have been observed: the prostate cancer prevention trial, for example, demonstrated that insulin secretion rate as reflected by c-peptide level is an important risk factor for high grade disease, but that this c-peptide-associated risk is specifically attenuated by finasteride (5). While there is considerable evidence that the hormonal consequences of positive energy balance lead to increased risk for many cancers, the possibility that high circulating levels of specific nutrient molecules may predispose to carcinogenesis or neoplastic progression is now receiving attention, and there is early evidence that branched chain amino acids (BCAA) may be important in this regard (6,7). BCAAs favor activation of mTOR, which increases proliferation as well as rate of oxidative phosphorylation (8), which in turn may increase oxidative DNA damage. Future laboratory and clinical research may identify key serum hormonal and metabolic analytes that are altered by effective prevention measures (and may even be the mediators of their effects), and these may serve as useful surrogate endpoints in clinical trials of proposed pharmacologic cancer prevention strategies, including metformin (9), as well as lifestyle and nutritional interventions. (1) Pollak M. Do cancer cells care if their host is hungry? Cell Metab. 2009 9(5):401-3 (2) Bao Y et al. A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. J Natl Cancer Inst. 2013;105(2):95-103 (3) Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12(3):159-69 (4) Zakikhani M et al. The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prev Res. 2008 1(5):369-75 (5) Neuhouser ML et al. Finasteride modifies the relation between serum C-peptide and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer Prev. Res. 2010 3(3):279-89 (6) Mayer J et al. Elevated BCAA are an early event in pancreatic carcinoma development. Nature Med., in press (7) Liu KA et al. Leucine supplementation differentially enhances pancreatic cancer growth in lean and overweight mice. Cancer Metab. 2014 31;2(1):6. (8) Morita M et al. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 2013;18(5):698-711. (9) Pollak M. Repurposing biguanides to target energy metabolism for cancer treatment. Nature Med. 2014 Jun;20(6):591-3. Citation Format: Michael N. Pollak. Metabolic approaches to cancer prevention. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL04-01.

Abstract A02: Integrative analysis identifies differential miRNA expression in HPV-positive head and neck squamous cell carcinoma including mir-9 overexpression and corresponding downregulation of the target YAP1

Abstract Background: HPV-positive (HPV+) head and neck squamous cell cancer (HNSCC) differs significantly from HPV-negative (HPV-) in terms of biology, response to treatment, and clinical outcome. The molecular mechanisms underlying these differences and the potential contribution of microRNA (miRNA) in regulating the behavior of HPV- disease are not well understood. Methods: We conducted an integrated analysis of miRNA expression as well as protein and mRNA expression from HPV+ and HPV - HNSCC to identify candidate genes and proteins that might be regulated by miRs. We first compared miRs in HPV+ (n=36) versus HPV- (n=243) cancers from The Cancer Genome Atlas (TCGA) to identify miRs that were differentially expressed between these groups (by t-test, p≤0.05, fold change≥2.8). Using TargetScan and the mirWalk systems, we then predicted potential targets for these miRs. Next, differences in the expression of predicted targets were evaluated by comparing levels of proteins (assessed using reverse phase proteomic arrays (RPPA)) and mRNA levels (by RNASeq) between HPV+ and HPV- tumors. Results: We identified eight miRs that differed significantly between HPV+ versus HPV- HNSCC tumors. Among these miRs, mir-9, mir-20b, mir-363, and mir-106a were higher in HPV+ tumors, while mir-767, mir-105, mir-1269, and mir-206 were present at lower levels. Predicted target genes of these miRs that were confirmed to be differentially expressed at the mRNA or protein level include YAP1, a known effector of the Hippo pathway and predicted target gene for mir-9. Specifically, HPV+ tumors demonstrated lower YAP1 mRNA expression (p=3.48E-05, fold change=-1.6) as well as lower levels of phosphorylated YAP 1 protein (p=.0015. fold change=-1.7). Other potential candidates identified include EEF2 (mir-106a target) and phosophorylated PDK1 (mir-363 target), which both exhibited lower protein levels in HPV+ cancer. Conclusions: Our analysis identified eight miRs that differed significantly between HPV + and HPV- cancers. Through an integrative analysis, we identified the YAP1 pathway as a potential target for mir-9 , a miR that has previously been found to be elevated in other cancers, including non-small cell lung cancer. These data suggest that miRs may contribute to differences between HPV+ and HPV- HNSCCs. Further investigations on the role of miRs in the pathogenesis of HPV+ and HPV- OSCCs are ongoing. Citation Format: Claudia Isabel Heymach, Lixia Diao, Pan Tong, Patrick Kwok Shing Ng, Gordon B. Mills, Jing Wang, Lauren Byers. Integrative analysis identifies differential miRNA expression in HPV-positive head and neck squamous cell carcinoma including mir-9 overexpression and corresponding downregulation of the target YAP1. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A02.

Abstract A36: Recreational physical activity and the risk of pancreatic cancer in the California Teachers Study

Abstract Background: Pancreatic cancer is highly fatal; thus, preventive strategies are needed. Besides cessation of cigarette smoking, physical activity may reduce pancreatic cancer risk by improving insulin sensitivity and glucose tolerance. However, the existing data lack consistency and generally, physical activity has been measured only at one time point. We examined recreational physical activity during different periods of life as well as a cumulative, long-term physical activity measure in relation to the risk of pancreatic cancer in California Teachers Study (CTS). Methods: 120,921 women aged 22-84 years participating in the CTS with no history of pancreatic cancer were followed from 1995 through 2011. The self-administered baseline (1995-1996) questionnaire captured information on demographics, moderate and strenuous recreational physical activity during high school, between ages 18 and 24, 25 and 34, 35 and 44, and 45 and 54 years, and in the three years before baseline, and potential risk factors for pancreatic cancer such as body mass index (BMI), diabetes, alcohol consumption, cigarette smoking, and dietary fat intake. Incident diagnoses of invasive pancreatic cancer were identified through annual linkages with the California Cancer Registry. We calculated average number of hours per week for recreational physical activity during different periods of life and combined them into a long-term physical activity measure. We fit Cox proportional hazards models to data to estimate the hazard ratios (HR) of pancreatic cancer risk and their corresponding 95% confidence intervals (CI) associated with moderate and strenuous physical activity in each age/time period and over the “long-term.” For each analysis, the least active group (≤0.5 hours/week) served as the reference group. Multivariable models were stratified by age at baseline (in single years) and were adjusted for race, total pack-years of cigarette smoking, alcohol consumption and total dietary fat intake in the year before baseline, diabetes, and BMI at baseline. Furthermore, we tested for a linear trend in risk by fitting the median value of physical activity within each category; we also examined whether BMI, smoking status, and alcohol intake modified any physical activity association. Results: During 1,715,690 person-years of follow-up, 429 women were diagnosed with invasive pancreatic cancer. The average age at diagnosis of pancreatic cancer was 74 years. In the multivariable model, women with higher levels of long-term moderate/strenuous physical activity had lower risk of pancreatic cancer than the least active women (≤0.5 hours/week) although the 95% CI included one (2.51-5.5 hours/week: HR=0.76; 95% CI=0.56-1.02, >5.5 hours/week: HR=0.85; 95% CI=0.63-1.15) and no linear trend in pancreatic cancer risk was observed (Ptrend=0.35). In the analysis of physical activity during different periods of life, we observed a marginally significant decreasing trend in risk with increasing physical activity during ages 18-24 years (Ptrend=0.05). The stratified analysis indicated a decreasing trend in pancreatic cancer risk with increasing physical activity during ages 18-24 years among women who were overweight or obese at baseline (Ptrend=0.006), who never smoked cigarettes (Ptrend=0.02), and who consumed <10 grams of alcohol per day in the year before baseline (Ptrend=0.02). No significant effect modifications were observed. Conclusions: The CTS data suggest that a higher level of recreational physical activity in early adulthood modestly reduces the risk of pancreatic cancer development in subgroups of women. However, we lacked sufficient statistical power to demonstrate effect modification. Larger studies are needed to understand whether the effect of physical activity on pancreatic cancer varies by age at activity, BMI, smoking status, or alcohol intake. Citation Format: Kayo Togawa, Huiyan Ma, Jane Sullivan-Halley, Jessica Clague, Susan Neuhausen, Eunjung Lee, Dennis Deapen, Leslie Bernstein. Recreational physical activity and the risk of pancreatic cancer in the California Teachers Study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A36.

Abstract B50: Differential influence of vitamin D on the tumor promoting eicosanoid PGE2 in women at increased breast cancer risk

Abstract Numerous lines of evidence point to the tumor promoting properties of prostaglandin (PG)E2. Preclinical studies have demonstrated the ability of both vitamin D (vitD) and celecoxib to downregulate the eicosanoid. We previously reported that vitD, but not the combination, significantly downregulated PGE2 in normal risk women. We hypothesized that there would be a similar or greater benefit of vitD alone, or in combination with celecoxib, in women at increased breast cancer risk. 40 women at increased breast cancer risk were prospectively enrolled and randomized in double blind fashion for one month (postmenopausal) or one menstrual cycle (premenopausal) to one of four daily treatment regimens: placebo, 400 IU vitD, 2000 IU vitD, or 2000 IU vitD + 400 mg celecoxib. Breast nipple aspirate fluid (NAF) and serum were collected. Both breast specific and systemic levels of PGE2 were measured. There was a significant increase (p=.02) in circulating levels of vitD after treatment in women receiving 2000 IU vitD with or without celecoxib, but not in women receiving placebo or 400 IU vitD. Celecoxib levels increased in those treated with celecoxib but not in the other groups. In the breast, as reflected in NAF, there was a 20% increase (p=.07) in PGE2 after treatment with 2000 IU vitD, with little change after treatment in the other groups. No treatment significantly changed circulating levels of PGE2. These findings suggest that, unlike in normal risk women, 2000 IU vitD may increase levels of a key cancer promoting enzyme in women of increased breast cancer risk. Supported in part with funds from the Komen Foundation and the Department of Defense. Citation Format: Wenyi Qin, Charles Walker, Edward Sauter. Differential influence of vitamin D on the tumor promoting eicosanoid PGE2 in women at increased breast cancer risk. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B50.

Abstract PL05-01: Obesity, IGF-1 and cancer prevention: Mechanistic insights from transdisciplinary studies

Abstract The prevalence of obesity, an established risk and progression factor for many cancers, has more than doubled over the past three decades in the US, with ~36% of adults currently obese. The mechanisms underlying the obesity and cancer connection are becoming increasingly clear and reveal several potential targets and strategies for breaking the obesity-cancer link. We have established in multiple genetically engineered mouse models (GEMMs) of mammary, pancreatic and other epithelial cancers that diet-induced obesity (DIO) increases serum levels of bioavailable insulin-like growth factor (IGF)-1, induces insulin resistance, and enhances tumor development and progression. In contrast the maintenance of a lean phenotype via a calorie restriction (CR) regimen decreases IGF-1 levels, improves insulin sensitivity, and inhibits cancer development and progression in these same models. Furthermore, biochemical, genetic and pharmacologic studies in GEMMS further suggest components of the mammalian target of rapamycin (mTOR) pathway, downstream of insulin and IGF-1 receptors, interact with inflammatory signals and provide important targets for disrupting the obesity-cancer link. Translational studies involving weight loss interventions in obese women at high risk for breast cancer show good concordance between mouse and human serum markers of energy balance-related hormones (including bioavailable IGF-1) and cytokines, as well as tissue mTOR signaling. We conclude from these transdisciplinary findings that several promising molecular targets (such as mTOR) are emerging for offsetting the procancer effects of obesity. Moreover, preclinical studies of several CR-mimetic agents (such as rapamycin, metformin, and several bioactive food components) provide further proof of the principle that mechanism-based approaches to break the obesity-cancer link by targeting mTOR and/or inflammation are plausible. Citation Format: Stephen D. Hursting. Obesity, IGF-1 and cancer prevention: Mechanistic insights from transdisciplinary studies. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL05-01.

Abstract A52: Oral contraceptive use and risk of colorectal polyps in a colonoscopy based study in western Washington state

Abstract Background: Most colorectal cancers arise from polyp precursor lesions, including advanced adenomas and a subset of serrated polyps, termed sessile serrated polyps. Growing literature on oral contraceptives (OC) use and risk of colorectal cancer suggests an inverse association. However, very little is known about the role of OC in the development of colorectal polyps. We investigated the relationship between OC use and the risk of subsets of colorectal polyps in a colonoscopy based study in western Washington State. Methods: Study participants were 20-79 year-old women enrollees at Group Health, an integrated health care system in Seattle, Washington who underwent a colonscopy for any indication from 1998-2007. Study eligible participants completed a structured interview to collect risk factor information, including reproductive history and exogenous hormone use. OC use was categorized according to ever use, recency of use, and duration of use. Participants were diagnosed as having adenomas (n=298), serrated polyps (n=336), both types of polyps (n= 105) or as polyp-free controls (n=615) on the basis of a standardized pathology review. Multivariable polytomous logistic regression was used to compare case groups with polyp-free controls and other case groups; odds ratios (OR) and 95% confidence intervals were estimated adjusted for age, race, educational status, body mass index, smoking, alcohol intake, anti-inflammatory drug use, use of postmenopausal hormones, parity and age at first birth. Results: Ever use of OC was not associated with risk for adenomas (adjusted OR 0.82, 95% CI 0.57-1.20) or serrated polyps (adjusted OR 0.93, 95% CI 0.64-1.36) while the risk for synchronous presence of both types of polyps was elevated (adjusted OR 1.43, 95% CI 0.77-2.67) (p=0.39 for the three polyp subtypes). Strength of association did not vary significantly between adenomas and serrated polyps for duration of use (p=0.43) and time since last use (p=0.75). Additionally, the associations did not differ significantly by age, lesion severity (advanced vs. nonadvanced for adenomas, sessile serrated vs. hyperplastic for serrated polyps), or location (right vs left) for either adenomas or serrated polyps. Conclusions: We observed no strong evidence that adenomas or serrated polyps were associated with ever use of OC pills. Although the majority of studies suggest a reversible effect of exogenous postmenopausal hormones on colorectal neoplasia, we did not find any association between time since last use of OC pills and development of either types of polyps. Further larger studies are needed to better understand the mechanistic processes through which oral contraceptives may be associated with the development of adenomas and serrated polyps. Citation Format: Sheetal Hardikar, Andrea N. Burnett-Hartman, Polly A. Newcomb. Oral contraceptive use and risk of colorectal polyps in a colonoscopy based study in western Washington state. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A52.

Abstract A25: Television watching, other sedentary behaviors and colorectal cancer survival in men

Abstract Background: Independent of physical activity, television (TV) watching, a major sedentary behavior in the United States, is associated with increased risk of obesity and diabetes, established risk factors for colorectal neoplasia. Although data suggest probable positive associations between sitting time, in particular time spent watching TV, and risk of colorectal adenoma and cancer, the impact of sedentary behaviors on mortality among colorectal cancer patients is unclear. Methods: We assessed the association between pre- and post-diagnostic time spent sitting while watching TV as well as other sedentary behaviors (other sitting at home and sitting at work/driving) and mortality from colorectal cancer and other causes, as well as overall mortality among nonmetastatic colorectal cancer cases identified between 1986 to 2010 from the Health Professionals Follow-up Study. Starting from 1988, participants reported average weekly time spent sitting watching TV/VCR biennially, and hours of other sitting at home and sitting at work/driving since 1990. For analyses of prediagnosis sedentary behavior, we calculated cumulative hours of sitting to the time of diagnosis to capture long-term sitting behavior. For postdiagnosis analyses, the first assessment collected at least 6 months but no more than 3 years after diagnosis was used to avoid assessment during the period of active treatment. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 858 and 662 eligible colorectal cancer patients were included in the analysis of prediagnostic and postdiagnostic TV watching, respectively. More time spent sitting watching TV before diagnosis was significantly associated with increased risk of colorectal cancer-specific mortality but not with mortality from other causes or overall mortality in multivariate analyses adjusted for age and years of diagnosis, stage, grade and location of the tumor, and smoking status. Further adjusting for leisure-time physical activity or potential mediators including body mass index and dietary score did not appreciably change the estimates. The HRs (95% CIs) of colorectal cancer-specific mortality across categories of prediagnostic TV watching (0-6, 7-13,14-20, ≥21 h h/wk) were 1.00 (referent), 0.82 (0.55-1.24), 1.13 (0.72-1.76), 2.10 (1.27-3.47) (P for trend=0.01). We combined the first three categories of TV watching based on the dose response relationship (HR for ≥21 vs < 21 h/wk=2.19; 95% CI 1.39-3.44) to assess potential effect modifications, and found that the association was slightly stronger among stage I and II than among stage III cancer patients, and among those with BMI ≥25 kg/m2 than among patients with BMI <25 kg/m2, although interactions were not significant. Similar associations were observed for colon vs rectal cancer, cancer diagnosed before vs after 2000, and those who engaged in <18 vs ≥ 18 MET (Metabolic Equivalent of Task)-hrs per week of physical activity. When restricted to mortality within 5-year after diagnosis, prolonged TV watching before diagnosis was also associated with higher overall mortality (HR for ≥21 vs < 21 h/wk=1.55; 95% CI 1.03-2.35). Other prediagnostic sedentary behaviors including sitting at home or at work/driving were not associated with mortality from colorectal cancer or other causes, as well as overall mortality. With limited power, we also observed that postdiagnostic time spent sitting watching TV was associated with higher but non-significant increased risk of colorectal cancer-specific mortality (HR for ≥21 vs < 21 h/wk=1.57; 95% CI 0.81-3.03). Conclusion: Prolonged TV watching is associated with higher colorectal cancer-specific mortality independent of leisure-time physical activity. Reducing sedentary behavior, in particular time spent sitting watching TV, may be important in the prognosis of colorectal cancer. Citation Format: Yin Cao, Jeffrey Meyerhardt, Andrew Chan, Charles Fuchs, Edward Giovannucci. Television watching, other sedentary behaviors and colorectal cancer survival in men. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A25.

Abstract PL02-03: Diet, nutrition, and cancer: Past, present, and future

Abstract For many years, Dr. John Milner was a champion for research on diet, nutrition and cancer. As part of his memorial symposium, this presentation will review the state of science on this topic, including a consideration of where the field has been, where it is today, and opportunities for future progress. The 1980s focused research on this topic, with the publication of several landmark reports, including the 1982 publication on “Diet, Nutrition and Cancer” by the U.S. National Academy of Sciences, which was followed by a Surgeon General's Report on Nutrition and Health in 1988 and several other landmark publications. The conclusions of these reports reflected a cautious optimism that diet might provide a strategy for cancer prevention, at least for selected cancers, and noted new directions for research to propel the field forward. Nearly a decade later (in 1997), another landmark report on nutrition and cancer was released, the World Cancer Research Fund/American Institute for Cancer Research report on “Food, Nutrition and the Prevention of Cancer: A Global Perspective,” which was updated in 2007 and continuously thereafter. The decades of research described in these reports demonstrate a substantial evolution in the scientific evidence base linking diet, nutrition and cancer prevention. As will be discussed, advances in dietary assessment and analysis, interpretation of dietary/nutrient data in relation to cancer risk, recognition of tumor heterogeneity, and consideration of hierarchy of research evidence have provided greater clarity to early findings in the field. Similarly, a new wave of technological advances, largely based in genetics/genomics, is now enabling exciting new lines of investigation into diet, nutrition and cancer. Dr. Milner was a passionate advocate for the incorporation of genetic and genomic technologies into nutrition research, and emphasized the value of mechanistically-based research for a more comprehensive understanding of the role of nutrition in carcinogenesis. The impact of his vision and leadership on emerging topics in diet, nutrition and cancer is evident as will be presented. Citation Format: Susan T. Mayne. Diet, nutrition, and cancer: Past, present, and future. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL02-03.

Abstract B06: Dietary intake in the relation between acculturation and obesity among healthy, Mexican-descent women

Abstract Background: Obesity increases risk for breast and other cancers. This is of concern among Hispanics who have higher rates of obesity when compared to non-Hispanic Whites. More versus less acculturated Hispanics often have diets high in simple sugars and low in fiber, which is proposed to contribute to adiposity. Therefore, we aimed to examine the associations between obesity, acculturation, and dietary intake among healthy, Mexican-descent women. Methods: A cross-sectional analysis was conducted among 1st and 2nd generation healthy Mexican-descent women (n=58) who were screened for participation in a controlled feeding study in Seattle, WA. Women were pre-menopausal, non-smoking, ages 18 to 45 years, with a body mass index (BMI) between 18.5 and 40.0 kg/m2. Additional exclusion criteria addressed a mix of medical and practical issues and included impaired glucose tolerance (fasting glucose ≥100mg/dL), current pregnancy or lactation, and heavy alcohol use, defined as ≥ 2 drinks/day. Analyses included demographics, acculturation measures, self-reported dietary intake (3-day food records) and measured anthropometrics. Dietary intake is reported as percentage of total energy. Comparisons across BMI categories were tested using general linear models for continuous dietary intake variables, while adjusting for age. Adjusted logistic regression models were used to calculate the odds ratio (OR) for overweight and obesity (BMI ≥25.0), as compared to normal weight (BMI <25.0) given dietary intake across acculturation measures. Results: Women in the study had lived in the US for 13.8 ± 6.4 years, 60% were born in Mexico, 64% self-identified as Mexican versus Mexican-American and 53% were overweight or obese. Overweight and obese women significantly (P <0.05) consumed less dietary fiber (17.1 vs 18.6 g/d) and vegetable protein (5.0 vs 5.6, as percentage of total energy) when compared to normal weight women. Among less acculturated women, a higher intake of dietary fiber (20.6 vs 17.1 g/d, 17% more) resulted in lower odds for being overweight or obese [OR=0.85 (0.73, 0.99)], while a higher intake of sucrose (54.3 vs. 36.6 g/d; 33% more), as percentage of total energy, resulted in higher odds for being overweight or obese among more acculturated women [OR=1.43 (1.07, 1.91)]. Conclusions: These results are consistent with the hypothesis that more acculturated women consume less dietary fiber and more simple sugars, which may contribute to overweight and obesity. Prevention efforts for obesity-related breast and other cancers should include dietary recommendations that encourage diets high in dietary fiber, while reducing the consumption of added sugars in this highly-at risk population. Citation Format: Margarita Santiago-Torres, Kara L. Breymeyer, Mario Kratz, Johanna W. Lampe, Lisa Levy, Marian L. Neuhouser. Dietary intake in the relation between acculturation and obesity among healthy, Mexican-descent women. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B06.