Risk In African American Women Research Articles

Abstract IA20: A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans

Abstract In addition to being frequently mutated in sporadic cancer, the p53 tumor suppressor also contains several coding region variants that alter function and can contribute to increased cancer risk. We previously published that the Pro47Ser variant of p53 exists in approximately 1-2% of individuals of African descent, and that this variation prevents a key phosphorylation event on p53, and reduces the ability of this protein to induce cell death (1). We recently published a mouse model for this variant, and show that this mouse develops a striking incidence of sporadic cancer, predominantly hepatocellular cancer but also including cancers of the pancreas, stomach, and intestine. In a cohort of African American women with breast cancer, we found evidence for an association of Pro47Ser with pre-menopausal cancer incidence (HR 1.7, p<0.025) (2). Mechanistically, we find that the Pro47Ser variant displays a very selective transcriptional defect compared to wild-type p53, for a subset of target genes involved in ferroptosis and metabolism (3). Metabolic studies on mouse and human cells, as well as our Pro47Ser mouse, indicate that there is a profound difference in metabolism, with cells and mice containing Pro47Ser showing a significant predilection for aerobic glycolysis instead of oxidative phosphorylation. Interestingly, this defect actually leads to an apparent increase in fitness in these mice. We recently conducted a drug screen to search for compounds that may be selectively efficacious in tumors containing the Pro47Ser variant; this analysis revealed several compounds with increased efficacy against Pro47Ser tumors, compared to identical tumors with wild-type p53 (4). Our combined data suggest that the Pro47Ser variant may underlie increased cancer risk in African Americans, and that we may be able to personalize therapy for individuals containing this variant. 1. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 2005;280(25):24245-51. PubMed PMID: 15851479. 2. Murphy ME, Liu S, Yao S, et al. A functionally significant SNP in TP53 and breast cancer risk in African-American women. NPJ Breast Cancer 2017;3:5. PubMed Central PMCID: PMC5445618. 3. Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016;30(8):918-30. PubMed Central PMCID: PMC4840298. 4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME. The African-specific S47 polymorphism of p53 alters chemosensitivity. Cell Cycle 2016;15(19):2557-60. PubMed Central PMCID: PMC5053554. Citation Format: Maureen E. Murphy. A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA20.

Abstract 5247: Aspirin use and estrogen receptor-negative breast cancer risk in African American women

Abstract Introduction: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of breast cancer; however, results of epidemiological studies have been mixed. Further, few previous studies investigated these associations among African American women and no studies that included African Americans evaluated whether associations differ by estrogen receptor (ER) status. Methods: To assess the relation of aspirin use to risk of ER+ and ER- breast cancer in African American women, we conducted a prospective analysis within the Black Women's Health Study, an ongoing nationwide cohort of 59,000 black women that began in 1995. On baseline and biennial follow-up questionnaires, women reported regular aspirin use (defined as use at least three days per week) and years of use. Acetaminophen use was queried similarly. Among women with available information on aspirin use, 1701 invasive breast cancers occurred during follow-up through 2015, including 962 ER+ and 492 ER- tumors. All cancers were confirmed through pathology reports or state cancer registry data. We used age-stratified Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of aspirin use with risk of ER+ and ER- breast cancer. All models adjusted for age at menarche, oral contraceptive use, parity, age at first birth, estrogen plus progestin use, body mass index, alcohol consumption, and use of other NSAIDs. Results: Compared to never use, current regular use of aspirin was associated with lower risk of breast cancer overall (HR 0.87; 95% CI 0.76, 1.00). The association was driven by a statistically significant inverse association for ER- breast cancer (HR 0.76; 95% CI 0.58, 0.99); for ER+ breast cancer, the corresponding HR was 0.92 (95% CI 0.77, 1.09). In contrast, we found no associations with acetaminophen use. Conclusions: Our observation of reduced risk of ER- breast cancer in relation to current regular use of aspirin is consistent with anti-inflammatory effects of aspirin, rather than hormone-dependent pathways. Aspirin may represent a potential opportunity for chemoprevention of ER- breast cancer; however, these findings require corroboration in additional studies. Citation Format: Kimberly A. Bertrand, Traci N. Bethea, Hanna Gerlovin, Patricia Coogan, Lucile L. Adams-Campbell, Lynn Rosenberg, Julie R. Palmer. Aspirin use and estrogen receptor-negative breast cancer risk in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5247.

Abstract A09: Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review

Abstract Certain residential characteristics in urban neighborhoods have shown to have negative impacts on health, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer risk, incidence, stage at diagnosis/late stage diagnosis, survival, and mortality in African Americans. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies that included populations of African American women, setting in “urban” areas, and a measure of a neighborhood or residential factor were reviewed. Three parameters related to neighborhood/residential factors were extracted, including neighborhood socioeconomic status (SES), residential segregation, and residential pollution. Eighteen studies were identified for systematic review. 10 studies showed significantly higher odds of late-stage diagnosis, higher mortality, and lower survival in African American women living in lower socioeconomic neighborhoods. One study showed slightly higher odds of upward neighborhood change and probability of distant metastasis at diagnosis of African American woman compared to White women (OR=1.24). Similarly, 5 studies showed significantly high associations between residential segregation and late-stage diagnosis, as well as high associations of residential segregation and higher mortality in African American women. Two studies assessed residential pollution on breast cancer risk. The first study showed a weak rate of breast cancer risk in African American women between differentiating levels of trihalomethane in public water (RR=1.2). The second assessed the association of magnetic field exposure and breast cancer risk and found that the odds of getting breast cancer were not significant in African American women (OR=1.02). This review provides a qualitative synthesis of major neighborhood and residential factors on breast outcomes in African American women. By enacting health policies and utilizing tools such as health informatics, steps can be taken to drive the breast cancer disparity down in this population. Citation Format: Brandi Patrice Smith, Zeynep Madak-Erdogan. Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A09.

Abstract 3012: Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review

Abstract Residential characteristics in urban neighborhoods impacts health and might be an important factor contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in African American women. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies including populations of African American women, setting in “urban” areas, and a measure of a neighborhood or residential factor were reviewed. Four parameters related to neighborhood or residential factors were extracted including: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. Our analysis showed that African American women living in low nSES have greater odds of late stage diagnosis and mortality. Furthermore, African American women living in segregated areas (higher percentage of Blacks) have higher odds of late stage diagnosis and mortality compared to White and Hispanic women living in less segregated areas (lower percentage of Blacks). Late stage diagnosis was also shown to be significantly higher in areas with poor mammography access and areas with higher Black residential segregation. Lastly, residential pollution did not affect breast cancer risk in African American women. Overall, this systematic review provides a qualitative synthesis of major neighborhood and residential factors on breast cancer outcomes in African American women. Citation Format: Brandi P. Smith, Zeynep Madak-Erdogan. Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3012.

Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

Inflammatory signatures distinguish metabolic health in African American women with obesity.

Obesity-driven Type 2 diabetes (T2D) is a systemic inflammatory condition associated with cardiovascular disease. However, plasma cytokines and tissue inflammation that discriminate T2D risk in African American women with obese phenotypes are not well understood. We analyzed 64 circulating cytokines and chemokines in plasma of 120 African American women enrolled in the Black Women’s Health Study. We used regression analysis to identify cytokines and chemokines associated with obesity, co-morbid T2D and hypertension, and compared results to obese women without these co-morbidities, as well as to lean women without the co-morbidities. We then used hierarchical clustering to generate inflammation signatures by combining the effects of identified cytokines and chemokines and summarized the signatures using an inflammation score. The analyses revealed six distinct signatures of sixteen cytokines/chemokines (P = 0.05) that differed significantly by prevalence of T2D (P = 0.004), obesity (P = 0.0231) and overall inflammation score (P < E-12). Signatures were validated in two independent cohorts of African American women with obesity: thirty nine subjects with no metabolic complications or with T2D and hypertension; and thirteen breast reduction surgical patients. The signatures in the validation cohorts closely resembled the distributions in the discovery cohort. We find that blood-based cytokine profiles usefully associate inflammation with T2D risks in vulnerable subjects, and should be combined with metabolism and obesity counselling for personalized risk assessment.

Genetic Variants in Immune-Related Pathways and Breast Cancer Risk in African American Women in the AMBER Consortium.

Background: Constitutional immunity shaped by exposure to endemic infectious diseases and parasitic worms in Sub-Saharan Africa may play a role in the etiology of breast cancer among African American (AA) women.Methods: A total of 149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based pathway analyses were conducted using the adaptive rank truncated product statistic for overall breast cancer risk, and risk by estrogen receptor (ER) status. Unconditional logistic regression analysis was used to estimate ORs and 95% confidence intervals (CIs) for single variants.Results: The top pathways were Interleukin binding (P = 0.01), Biocarta TNFR2 (P = 0.005), and positive regulation of cytokine production (P = 0.024) for overall, ER+, and ER- cancers, respectively. The most significant gene was IL2RB (P = 0.001) for overall cancer, with rs228952 being the top variant identified (OR = 0.85; 95% CI, 0.79-0.92). Only BCL3 contained a significant variant for ER+ breast cancer. Variants in IL2RB, TLR6, IL8, PRKDC, and MAP3K1 were associated with ER- disease. The only genes showing heterogeneity between ER- and ER+ cancers were TRAF1, MAP3K1, and MAPK3 (P ≤ 0.02). We also noted genes associated with autoimmune and atopic disorders.Conclusions: Findings from this study suggest that genetic variants in immune pathways are relevant to breast cancer susceptibility among AA women, both for ER+ and ER- breast cancers.Impact: Results from this study extend our understanding of how inherited genetic variation in immune pathways is relevant to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 27(3); 321-30. ©2018 AACR.

Urban Neighborhood and Residential Factors Associated with Breast Cancer in African American Women: a Systematic Review.

Residential characteristics in urban neighborhoods impact health and might be important factors contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in African American women. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies including populations of African American women, setting in "urban" areas, and a measure of a neighborhood or residential factor were reviewed. Four parameters related to neighborhood or residential factors were extracted including: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. Our analysis showed that African American women living in low nSES have greater odds of late stage diagnosis and mortality. Furthermore, African American women living in segregated areas (higher percentage of Blacks) have higher odds of late stage diagnosis and mortality compared to White and Hispanic women living in less segregated areas (lower percentage of Blacks). Late stage diagnosis was also shown to be significantly higher in areas with poor mammography access and areas with higher Black residential segregation. Lastly, residential pollution did not affect breast cancer risk in African American women. Overall, this systematic review provides a qualitative synthesis of major neighborhood and residential factors on breast cancer outcomes in African American women.

Type 2 Diabetes May Increase Breast Cancer Risk in African-American Women

Type 2 Diabetes May Increase Breast Cancer Risk in African-American Women

Relation between depressive symptoms and cytokines associated with cardio- metabolic risk in African American women

Cardiometabolic diseases are the most prevalent diseases in the United States. Depressive symptoms are considered to be significant risk factors for cardiometabolic diseases, however, it is not clear if the relation between depressive symptoms and cardiometabolic risk is applicable in diverse populations. We examined the relations of depressive symptom subtypes to cardiometabolic disease-associated cytokines in a sample of African-American women. Participants were 30 African-American women (average age = 59 years) living in low income neighborhoods of Washington, DC who completed the Center for Epidemiological Studies-Depression Revised scale (CESD-R) and provided blood samples. Multiple regression analyses examined whether the CESD-R total score and the CESD-R subscales (entered separately) were associated with IL-1b, IL-6, IL-8, and IL-18. Analyses were adjusted for age, average physical activity level (as measured using physical activity tracker data), and body mass index (BMI). Results showed that sadness, loss of interest, and worthlessness were associated with increased levels of both IL-1b and IL-18, however, only IL-1b was associated with greater feelings of depression (total score), fatigue, and poorer sleep. IL-6 and IL-8 were not shown to have any significant relationship with any depressive symptom subtypes. These results indicate that depressive symptoms in African American women are associated with increased levels of inflammation, suggesting that negative psychological well- being may modulate the immune system in a manner that increases risk for development of cardiometabolic diseases.

Pubertal growth and adult height in relation to breast cancer risk in African American women.

Adult height has been positively associated with breast cancer risk. The timing of pubertal growth-as measured by age at menarche and age at attained height-may also influence risk. We evaluated associations of adult height, age at attained height, and age at menarche with incidence of invasive breast cancer in 55,687 African American women in the prospective Black Women's Health Study. Over 20 years, 1,826 invasive breast cancers [1,015 estrogen receptor (ER) positive; 542 ER negative] accrued. We used multivariable Cox proportional hazards regression to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for associations with breast cancer overall and by ER status, mutually adjusted for the three factors of interest. Adult height was associated with increased risk of ER+ breast cancer (HR for ≥70 inches vs ≤63 inches: 1.44; 95% CI: 1.09, 1.89) but not ER- (corresponding HR: 1.16; 95% CI: 0.78, 1.71) (p heterogeneity = 0.34). HRs for attained height before age 13 versus age >17 were 1.30 (95% CI: 0.96, 1.76) for ER+ and 1.25 (95% CI: 0.80, 1.96) for ER- breast cancer. Results for age at menarche (≤11 vs ≥14 years) were similar for ER+ and ER- breast cancer (HR for breast cancer overall: 1.30; 95% CI: 1.12, 1.50). We confirmed height as a strong risk factor for ER+ breast cancer in African American women and identified early age at attained height as a risk factor for both ER+ and ER- breast cancer, albeit without statistical significance of the latter associations. While adult height and timing of pubertal growth are inter-related, our findings suggest that they may be independent risk factors for breast cancer.

Tubal ligation and ovarian cancer risk in African American women.

Tubal ligation has been associated with reduced risk of epithelial ovarian cancer (EOC) in studies of primarily white women, but less is known about the association in African American (AA) women. We sought to evaluate the associations among 597 invasive ovarian cancer cases and 742 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case-control study in 11 geographical areas in the US. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potentially confounding factors. An inverse association between tubal ligation and EOC was observed that was not statistically significant (OR 0.88, 95% CI 0.68-1.14). However, an inverse association with EOC risk was observed among women who had a tubal ligation at age 35years or older (OR 0.64; 95% CI 0.41-0.98), but not among those who had a tubal ligation before age 35 (OR 0.98; 95% CI 0.74-1.29) (p for interaction=0.08). The association also varied considerably by tumor subtype. A strong inverse association was observed for endometrioid tumors (OR 0.31, 95% CI 0.14-0.70), whereas associations with mucinous (OR 0.87, 95% CI 0.36-2.12) and serous (OR 0.94, 95% CI 0.71-1.24) tumors were weaker and not statistically significant. A statistically non-significant positive association for clear cell tumors (OR 1.84, 95% CI 0.58-5.82) was based on a low number of cases. Our findings show that tubal ligation may confer a reduced risk for EOC among AA women that is comparable to the associations that have been previously observed in primarily white populations.

Dietary Quality and Ovarian Cancer Risk in African-American Women.

This study evaluated 3 index-based dietary patterns-Healthy Eating Index (HEI)-2005, HEI-2010, and Alternate Healthy Eating Index (AHEI)-2010-in relation to ovarian cancer risk in African-American women. The study was conducted among 415 ovarian cancer cases and 629 age- and site-matched controls of African-American descent recruited from the population-based African American Cancer Epidemiology Study. Multivariable unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals between quartiles of dietary quality indices and ovarian cancer risk, adjusting for potential confounders. We found that higher AHEI-2010 scores, but not HEI-2005 or HEI-2010 scores, were associated with lower risk of ovarian cancer (comparing the highest quartile (4th) vs. lowest (1st), odds ratio (OR)=0.66, 95% confidence interval (CI): 0.45, 0.98; P for trend=0.05). When stratified by menopausal status, no noteworthy associations were observed among premenopausal women. However, among postmenopausal women, greater adherence to HEI-2010 (quartile 4 vs. quartile 1, OR=0.57, 95% CI: 0.36, 0.92; P for trend=0.03) and AHEI-2010 (quartile 4 vs. quartile 1, OR=0.49, 95% CI: 0.31, 0.78; P for trend=0.01) were inversely associated with ovarian cancer. Our findings indicate that adherence to an overall healthy dietary pattern may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal African-American women.

Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium.

Background: Alcohol is a recognized risk factor for invasive breast cancer, but few studies involve African American women.Methods: The current analysis included 22,338 women (5,108 cases of invasive breast cancer) from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. The association between number of alcoholic drinks per week (dpw) and breast cancer was estimated using logistic regression, adjusting for potential confounders, and stratifying by breast cancer subtype.Results: Approximately 35% of controls were current drinkers at interview. Women who reported current drinking of ≥14 dpw had an elevated risk of breast cancer compared with light drinkers (>0-<4 dpw) [adjusted OR (ORadj), 1.33; 95% confidence interval (CI), 1.07-1.64]. We observed elevated risk among women drinking ≥7 dpw for ER - [ORadj, 1.31; 95% CI, 1.00-1.72], PR - [ORadj, 1.28; 95% CI, 1.00-1.63], HER2 - [ORadj, 1.36; 95% CI, 1.09-1.70], and triple-negative [ORadj, 1.39; 95% CI, 0.98-2.00] molecular subtype. Among receptor-positive cases, ORs remained elevated but attenuated relative to receptor-negative cases. Sensitivity analysis of age-defined windows of exposure (<30 years, 30-49, 50+ years of age) did not reveal variation in patterns of association. Risk associated with alcohol intake did not vary significantly by oral contraceptive use, smoking status, or menopausal status.Conclusions: Among African American women, similar to women of European descent, drinking ≥7 alcoholic dpw was associated with an increased risk of breast cancer regardless of subtype.Impact: Alcohol intake is a modifiable risk factor for breast cancer, and reduced intake among African American women should be encouraged. Cancer Epidemiol Biomarkers Prev; 26(5); 787-94. ©2017 AACR.

Supplemental Selenium May Decrease Ovarian Cancer Risk in African-American Women

BackgroundTo our knowledge, no previous study has evaluated the associations of antioxidant intake with the risk of ovarian cancer in African-American women, who are known to have high mortality from the disease. ObjectiveWe sought to evaluate these associations among 406 ovarian cancer cases and 632 age- and site-matched controls of African-American descent recruited from AACES (African American Cancer Epidemiology Study), a population-based, case-control study in 11 geographical areas within the United States. MethodsMultivariable logistic regression models were used to estimate ORs and 95% CIs adjusted for a wide range of potentially confounding factors, including age, region, education, parity, oral contraceptive use, menopause, tubal ligation, family history, body mass index (BMI), smoking status, total energy, and physical activity. ResultsWomen with the highest intakes of supplemental selenium (>20 μg/d) had an ∼30% lower risk of ovarian cancer than those with no supplemental intake (OR: 0.67; 95% CI: 0.46, 0.97; P-trend = 0.035). This inverse association was stronger in current smokers (OR: 0.13; 95% CI: 0.04, 0.46; P-trend = 0.001). There was no association with dietary selenium. The associations with carotenoid intakes were weak and nonsignificant (P = 0.07–0.60). We observed no association with dietary or supplemental intake of vitamin C or vitamin E. There were no appreciable differences in results between serous and nonserous tumors. ConclusionsThese findings provide the first insights, to our knowledge, into the potential association between antioxidants and ovarian cancer in African-American women, indicating potential inverse associations with supplemental selenium.

Field Experiences in Breast Cancer Research among African American Women

Despite many recent improvements in the health of Americans, substantial differences still exist among racial and ethnic groups. The frequently cited explanation for the disparity in health care for African Americans is lack of access to quality health care. Health care disparities are further complicated by increasing breast cancer rates of African American women without reduction of mortality rates. African American women have the highest breast cancer death rates. Despite all the gains that have been made in clinical, basic, and behavioral research, African American women continue to lag behind and remain disproportionately affected by this disease. In this qualitative pilot study, factors contributing to breast cancer risk in African American women were explored. Data was collected in four focus group sessions, where the study’s participants were asked questions related to their perceptions of health status, lifestyles, and health care access. Cultural values had a major impact relating to food preferences, food preparation and seeking health care. These participant narratives provide insight into issues regarding their breast cancer risks and suggestions for future research.

Lifetime number of ovulatory cycles and epithelial ovarian cancer risk in African American women.

Incessant ovulation has been consistently linked to epithelial ovarian cancer (EOC). Although reproductive characteristics differ substantially by race, the association between incessant ovulation and EOC has been evaluated only in populations of predominantly white women. In the present study, we examined the association between lifetime number of ovulatory cycles (LOCs) and EOC risk among African American (AA) women. We used data from 534 cases and 722 controls enrolled in the African American Cancer Epidemiology Study. LOCs were determined using the standard method, with modifications to include episodes of irregular or missed periods. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between LOCs and EOC risk overall and by age, while adjusting for appropriate confounders. The mean number of LOCs was 378.2 ± 105.8 for cases and 346.4 ± 117.3 for controls. Women in the highest tertile of LOCs had 59% higher odds of EOC compared to women in the lowest tertile (OR = 1.59; 95% CI = 1.15-2.20). When examining this relationship by age, the positive association with EOC was stronger among women <50years of age (OR for highest vs. lowest tertile = 2.61; 95% CI = 1.15-5.94), followed by women aged 50-60years (OR = 2.27; 95% CI = 1.30-3.94). Yet, no association was present among women aged >60years (OR = 0.79; 95% CI = 0.45-1.40). In a population of AA women, we observed a positive association between LOCs and EOC risk, providing further support for the hypothesis that incessant ovulation contributes to the etiology of EOC.

A functionally significant SNP in TP53 and breast cancer risk in African-American women

A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in TP53 tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08–2.76; p-value = 0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.

Abstract B51: Dairy, calcium, vitamin D and ovarian cancer risk in African-American women

Abstract Background: Ovarian cancer is the leading cause of death from gynecologic cancers in the US. Currently there is no reliable screening available for ovarian cancer. Most cases are diagnosed at an advanced stage, with a poor survival rate. Therefore, a better understanding of the etiology and prevention is especially important for ovarian cancer. It has been hypothesized lactose in dairy may have a direct toxicity effect on oocytes, while the other two abundant nutrients from dairy foods, calcium and vitamin D, may have anti-tumorigenic properties. In addition to food and supplemental intakes, vitamin D in humans can also be achieved through skin synthesis upon sun exposure. However, darker skin color may reduce the penetration of ultraviolet-B, resulting in the lower cutaneous synthesis of vitamin D. This, together with the tendency of African Americans (AAs) to have lower consumption of vitamin D and calcium from dietary and supplemental sources, place AA women at risk for vitamin D and calcium deficiency. Objective: To evaluate intakes of dairy foods, lactose, calcium, and vitamin D exposure (through diet, supplement and sunlight) and the risk of ovarian cancer among AA women. Methods: We evaluated these associations among 490 ovarian cancer cases and 656 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case-control study in 11 geographical areas in the US. Cases were identified through rapid case ascertainment and age- and site-frequency matched controls were identified by random-digit-dialing. Information on risk factors related to ovarian cancer was collected by a computer-assisted telephone interview. Daily hours spent outdoors in daylight were asked separately on weekdays or weekends, and in summer or the rest of the year. Dietary information was assessed via a self-administered Block 2005 food frequency questionnaire (FFQ). Supplemental intake of calcium or vitamin D including multivitamin sources was also collected. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for relevant sociodemographic, reproductive, and lifestyle risk factors. Results: In the multivariable- and mutually-adjusted model, whole milk consumption was significantly associated with increased ovarian cancer risk (OR=1.85 comparing consumers with above-median intake vs. non-consumers, 95% CI: 1.05-3.27; p-trend: 0.023). No association was observed for skim/low-fat milk, cheese or yogurt. Lactose intake was found to increase ovarian cancer risk [OR=1.97 comparing the highest quartile (Q4) vs. lowest (Q1), 95% CI: 1.25-3.10; p-trend: 0.008]. Calcium intake was consistently associated with a decreased risk, with a similar OR for calcium from food, supplement, or total from both sources when comparing the highest to the lowest intake category. For example, total calcium intake was associated with a 49% decreased OR comparing Q4 vs. Q1 (95% CI: 0.30-0.86; p-trend: 0.009). Although we found no association with total and dietary vitamin D intakes, more daylight hours spent outdoors in summer months predicted a lower risk of ovarian cancer (OR=0.71 comparing Q4 vs. Q1, 95% CI: 0.51-0.99; p-trend: 0.049). Conclusion: Our findings suggest, for the first time, that sun exposure in summer months and a high-calcium, low-lactose diet may decrease the risk of ovarian cancer in AA women. Considering that there is no effective screening tool for ovarian cancer and the poorer survival of AA patients, if replicated in future studies these results open up potential preventive strategies through lifestyle or dietary modifications. Citation Format: Bo Qin, Patricia G. Moorman, Anthony J. Alberg, Jill S. Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, Ellen Funkhouser, Edward S. Peters, Ann G. Schwartz, Paul Terry, Joellen M. Schildkraut, Elisa V. Bandera. Dairy, calcium, vitamin D and ovarian cancer risk in African-American women. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B51.

Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium

Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium