Clinic-based Case-control Study Research Articles

Statin use and risk of pancreatic cancer: results from a large, clinic-based case-control study.

Statins are cholesterol-lowering medications with pleiotropic effects, including alterations in growth signaling, as well as immunomodulatory and anti-inflammatory effects that may alter cancer risk. Evidence from previous epidemiologic studies is inconsistent about whether statin use is associated with a reduced risk of pancreatic cancer (PC). Patients with confirmed diagnoses of PC (cases) were recruited from medical and surgical oncology clinics, with controls (frequency-matched by sex and age) recruited from general medicine clinics, at a high-volume academic medical center over a 6-year period (2006-2011). Direct interviews were conducted with an epidemiological risk factor questionnaire covering topics such as medical history, lifestyle factors, and medication usage. Adjusted multivariable logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risk of PC. Data were obtained from 536 cases and 869 controls. Ever use of statins was associated with a 34% reduced PC risk (OR, 0.66; 95% CI, 0.47-0.92). In sex-stratified analyses, risk was statistically significantly reduced in men only (OR for men, 0.50; 95% CI, 0.32-0.79; OR for women, 0.86; 95% CI, 0.52-1.43). Duration of use was inversely associated with PC risk (>10-year use: overall OR, 0.51; OR for men, 0.41; 95% CI, 0.21-0.80; P(trend) = .006). This is the largest case-control study to demonstrate an inverse association between statin use and PC risk. Risk reduction in statin users appears to be sex-specific and is more pronounced in long-term users. Further research is warranted to better characterize this association and clarify the roles of underlying biologic mechanisms.

Diabetic macular ischaemia is associated with narrower retinal arterioles in patients with type 2 diabetes.

Diabetic macular ischaemia (DMI) is an important cause of visual loss in patients with diabetes, but its relationship to the larger retinal vessels is unknown. We examined whether retinal vessel calibre is related to DMI. Clinic-based case-control study of patients with type 2 diabetes. The presence and severity of DMI was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) protocols from fundus fluorescein angiographic (FFA) images. Custom software was used to quantify the greatest linear dimension and area of the foveal avascular zone (FAZ). Retinal vessel calibre was measured using a semi-automated software on fundus fluorescein images. Of 53 patients examined, 18 (34%), 18 (34%) and 17 (32%) had no/mild, moderate and severe DMI, respectively. Persons with moderate or severe DMI had narrower mean retinal arteriolar calibre than persons with no/mild DMI (140.6 μm 95% confidence interval (CI) 134.7, 146.4 versus 150.7 μm, 95% CI 142.5, 158, p = 0.04). The association remained after multivariate adjustment for age, gender, previous panretinal photocoagulation, neovascularization at the disc and elsewhere and diabetic retinopathy severity. Increased FAZ size was also associated with narrower arteriolar calibre. Retinal venular calibre and arteriole to venule ratio (AVR) were not associated with DMI. Retinal arteriolar narrowing was associated with moderate-to-severe macular ischaemia in eyes with diabetic retinopathy. This suggests that larger vessels other than capillaries may also be associated with DMI.

Regular Chinese Green Tea Consumption is Protective for Diabetic Retinopathy: A Clinic-Based Case-Control Study.

Objective. To determine the association between regular Chinese green tea consumption and the risk of diabetic retinopathy (DR) in diabetic patients in China. Methods. 100 DR patients and 100 age-sex-matched diabetic controls without retinopathy were recruited in a clinic-based, case-control study. DR was defined from retinal photographs and detailed information on Chinese green tea consumption of the participants was collected through a face-to-face interview. Results. The crude odds ratio [OR] of Chinese green tea consumption for DR was 0.49 (95% confidence interval: 0.26–0.90). When stratified by sex, the protective effect of Chinese green tea consumption on DR was statistically significant in women (P = 0.01) but not in men (P = 0.63). After adjusting for age, sex, and other confounders, DR was significantly associated with Chinese green tea consumption (OR = 0.48; P = 0.04), higher systolic blood pressure (OR = 1.02; P = 0.05), longer duration of diabetes (OR = 1.07; P = 0.02), and the presence of family history of diabetes (OR = 2.35; P = 0.04). Conclusions. Diabetic patients who had regularly drunk Chinese green tea every week for at least one year in their lives had a DR risk reduction of about 50% compared with those who had not. Regular Chinese green tea consumption may be a novel approach for the prevention of DR.

Risk factors for pancreatic neuroendocrine tumors: a clinic-based case-control study.

Pancreatic neuroendocrine tumors (PNETs) are uncommon, and little is known about their risk factors and association with other cancers. We evaluated whether the following risk factors known to be associated with pancreatic adenocarcinoma are also associated with PNETs: smoking, alcohol use, family history of PNET, and other cancers, and personal history of diabetes as potential risk factors. Patients with PNETs seen at Mayo Clinic Rochester between 2000 and 2011 were compared with controls seen for a general medical evaluation. Patients and controls completed the same questionnaires. After excluding insulinoma and high-grade PNETs, 355 cases were evaluated, and 309 were matched to 602 controls (2:1) on age, sex, and region of residence. Personal smoking history was not associated with PNETs. Alcohol use was less common among cases (54% vs 67%, P < 0.001). Cases were more likely to report a family member with sarcoma (P = 0.02), PNET (P = 0.02), gallbladder cancer (P = 0.02), ovarian cancer (P = 0.04), and gastric cancer (P = 0.01). There was no association with other cancers in family members. Diabetes was more commonly reported by cases than controls (19% vs 11%, P < 0.001). With the exception of diabetes, risk factors that are associated with pancreatic adenocarcinoma are not risk factors for PNETs.

Abstract B29: Case-control study of metabolic syndrome and breast cancer in Puerto Rico

Abstract Background: Breast cancer is the leading cancer type among women in the United States (US) and Puerto Rico (PR); incidence rates of breast cancer have increased in both of these populations in the last decades. In fact, Puerto Rico has highest prevalence of diabetes among all US states and territories. Diabetes, obesity and the metabolic syndrome (MS) are rapidly increasing in Hispanic populations, and research on the impact of these conditions on breast cancer among Hispanics is scarce. Objectives: This study assessed the association of MS with breast cancer among Hispanic women in PR. The secondary aim was to assess the association of the individual components of the MS (hyperglycemia, dyslipidemia, abdominal obesity and elevated blood pressure) with breast cancer. Methods: A matched clinic-based case-control study of 226 Hispanic women was performed between 2011 and 2013. One hundred thirteen cases and 113 controls were recruited in four clinics/hospitals in Puerto Rico and were individually matched by age (±5 years), menopausal status and recruitment site (response rate of 83% for cases and 84% of controls). Data collection procedures included a structured questionnaire, anthropometric and blood pressure measurements. According to the AHA/NHLBI definition, a woman was defined to have the MS if she had at least 3 of the following risk factors: waist circumference ≥35 inches, 2) triglycerides ≥150 mg/dL, 3) HDL &amp;lt;50 mg/dL, 4) blood pressure ≥130/85 mm Hg and 5) fasting glucose ≥100 mg/dL. Conditional logistic regression models were used to describe the association of the MS and its individual components with breast cancer. Results: Mean age of participants was 54.5 ±12.6 years. Prevalence of the MS was 53.2% among cases and 42.0% among controls. No significant differences were observed between cases and controls with regard to income, health care coverage, parity or smoking habits. Nonetheless, cases had significantly (p&amp;lt;0.05) lower educational attainment than controls. After adjusting for educational attainment, the MS was marginally (p=0.09) associated with higher odds of breast cancer (OR=1.82, 95% CI=0.92-3.61). Elevated fasting glucose (OR=1.74, 95% CI=0.94-3.23, p=0.08) was also marginally associated to higher odds of breast cancer; however, high triglycerides (OR=1.22, 95% CI=0.67-2.20), elevated blood pressure (OR=1.68, 95% CI=0.88-3.18, p=0.11), elevated waist circumference (OR=1.55, 95% CI=0.86-2.81) and low HDL-C (OR=1.01, 95% CI=0.56-1.81) were not significantly associated with breast cancer. Conclusions: This pilot study found marginal evidence of an association of the MS and elevated fasting glucose with breast cancer in a population of Hispanic origin. Future studies should assess this association using a larger sample size and considering the impact of tumor subtypes on breast cancer risk. Grant Support: The project was supported by U54CA96297 and U54CA96300 from the UPR/MDACC Partnership for Excellence in Cancer Research, NCI &amp; by the RCMI-Clinical Research Center grant G12RR03051 from the UPR Medical Sciences Campus. Citation Format: Ana Patricia Ortiz, Cynthia Perez, Edna Mora, Damarys Santiago, Carola T. Sánchez, Cristina Muñoz, Marievelisse Soto, Mong-Hong Lee. Case-control study of metabolic syndrome and breast cancer in Puerto Rico. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B29. doi:10.1158/1538-7755.DISP13-B29

ED-05 * GENDER AND REPRODUCTIVE FACTORS IN RELATION TO SURVIVAL IN GLIOBLASTOMA

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal primary tumor of the brain. Known clinical prognostic factors include patient age, surgical extent of tumor resection (EOR), and functional performance (Karnofsky) status (KPS). A few studies have suggested differential survival by gender though to our knowledge no study has examined the prognostic impact of reproductive history and hormonal exposures in women. We evaluated gender-specific mortality in a large cohort of GBM patients that underwent current standard of care and investigated clinical, tumor, and reproductive factors associated with gender-specific differences in survival. METHODS: Analyses were based on 550 patients with GBM (324 men and 226 women) diagnosed 2007-2012 and enrolled in a clinic-based case-control study conducted at medical centers in the Southeast. Information on reproductive and hormonal exposures in women was available from the study interview. RESULTS: Deaths from GBM were documented in 449 patients a median of 17.2 months following diagnosis (16.0 months in men and 18.6 months in women). Men and women were similar in age at diagnosis (median of 59 and 60 years, respectively; P= 0.992), education (41% and 39%, respectively, held a college degree; P= 0.749), KPS (median of 90% in both groups; P = 0.167), and EOR (32% and 29%, respectively, with gross total resection; P= 0.547). A college degree or higher education was independently associated with prolonged survival (multivariate-adjusted p = 0.003). Adjusting for age, education, EOR and KPS, the hazard of death was significantly greater in men (Hazard Ratio (HR): 1.25; 95% Confidence Interval (CI): 1.03, 1.51; p = 0.026). When compared to men, a reduced hazard was observed among parous women (HR: 0.78; p = 0.022) and in those that ever used hormonal replacement therapy (HR: 0.67; p = 0.016) controlling for other covariates. CONCLUSIONS: Reproductive history and exogenous hormones may contribute to a female survival advantage in patients with GBM.

Abstract 2164: Age at attainment of adult height and risk of primary brain tumors

Abstract Brain tumors represent a small fraction of primary cancers diagnosed each year. However, the disproportionate mortality and morbidity burden associated with brain tumors merits a greater understanding of their cause. Beyond ionizing radiation, few environmental exposures are confirmed to cause brain tumors in humans. A taller stature has been linked to increased risk in several studies. Furthermore, we and others have reported that risk varies with body weight at age 21 though not later in life. These findings suggest a potential role for the myriad of factors involved in adolescent growth with glioma risk. The purpose of this analysis was to further elucidate the relation of height and adolescent growth rate on primary brain tumor risk. The analysis included 1045 glioma cases, 274 meningioma cases and 1242 community controls enrolled in a clinic-based case-control study. In a structured interview participants reported height at age 21 and age at completion of linear growth. Multivariate logistic regression was used to compute odds ratios (OR) and 95% Confidence Intervals (CI) associated with age at attainment of maximum adult height (‘age-HT’) adjusted for age, race, gender, education, and state of residence. Among controls, the median age at height attainment was 17 in men (interdecile range: 15-19 years) and 16 in women (interdecile range: 13-18 years). Age-HT had no association with the risk of meningioma (P= 0.284). However, we observed a statistically significant positive association with the risk of glioma (P&amp;lt;0.001): for each additional year at which adult height was attained risk of glioma was increased 14% in men (OR: 1.14; 95% CI: 1.06, 1.24) and 11% in women (OR: 1.11; 95% CI: 1.04, 1.19). Persons with an age-HT ≥ 19 had nearly twice the risk of glioma (OR: 1.94; 95% CI: 1.36, 2.75) when compared to persons with age-HT ≤ 15, with similar results observed in men (OR: 2.11; 95% CI: 1.24, 3.60) and women (OR: 1.84; 95% CI: 1.07, 3.17), and in high grade (OR: 1.77; 95% CI: 1.18, 2.64) and lower grade (OR: 2.72; 95% CI: 1.59, 4.65) tumors. Among controls, adult height and age-HT were uncorrelated both in men (Pearson r = -0.03) and in women (Pearson r = 0.09). When we considered the association of age-HT by tertile of adult height (defined by gender), a statistically significant positive association was observed with increasing increment in age-HT in the lowest (OR: 1.16; P = 0.003) and middle tertile (OR: 1.18; P &amp;lt; 0.001), whereas no association was observed in the highest (OR: 1.01; P = 0.881) tertile of adult height. To our knowledge, this is the first report linking age at completion of linear growth with subsequent risk of glioma. A postulated mechanism is that a prolonged growth phase may increase exposure to growth factors that enhance glioma risk. Null findings in those attaining a tall stature, if not due to chance, suggest complex interactions with the timing and intensity of risk-promoting exposures. These findings warrant further study. Citation Format: Rebecca B. Little, Louis Burton Nabors, Jeffrey J. Olson, Zachary J. Thompson, Melissa H. Madden, Renato V. LaRocca, Peter A. Forsyth, Reid C. Thompson, Kathleen M. Egan. Age at attainment of adult height and risk of primary brain tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2164. doi:10.1158/1538-7445.AM2014-2164

Abstract 2160: Metformin use is not associated with pancreatic cancer risk in a clinic-based case-control study conducted in the San Francisco Bay Area, California

Abstract Patients with pancreatic cancer (PC) are commonly diagnosed at advanced stages of the disease, at which point cure is no longer possible. A better understanding of risk or protective factors for PC may inform prevention and/or early detection strategies. Metformin, a commonly used drug for type II diabetes (DM2), has been shown in some observational clinical studies to reduce the risk of several cancer types, including PC. Its antineoplastic effects occur through inhibition of mammalian target of rapamycin (mTOR) and induction of cell cycle arrest and apoptosis, among other mechanisms. The current case-control study addresses two distinct research questions: whether metformin use is associated with PC risk among those with DM2, and whether metformin modulates the risk of PC associated with DM2. We recruited 536 cases and 869 controls, predominantly from University of California, San Francisco (UCSF) medical and surgical oncology clinics (cases) and general medicine clinics (controls), over a six-year period (2006-2011). Controls were frequency-matched to cases by sex and age in 5-year groups. Case diagnoses were confirmed by patient medical record and cancer registry data. Direct interviews were conducted by trained interviewers using an epidemiological risk factor questionnaire. The association between metformin use and PC risk among diabetics was analyzed using propensity score-weighted unconditional logistic regression, whereas the effect of metformin use on the association between DM2 and PC in the total study population was analyzed using standard multivariable logistic models. Metformin was the most common anti-diabetic drug used by DM2 study participants (66.5%). Among DM2 participants (N=170), ever use of metformin was not associated with PC risk in adjusted models (OR: 1.01, 95%CI: 0.61-1.68). Similarly, duration of metformin use was not statistically significantly associated with PC risk when also adjusted for DM2 duration. Among the total study population (N=1405), DM2 was not statistically significantly associated with PC risk (adjusted OR: 1.28, 95%CI: 0.81-2.00). However, risk was inversely associated with DM2 duration; participants whose DM2 was diagnosed 1-5 years prior to PC diagnosis/interview were at markedly increased risk (OR: 2.47, 95%CI: 1.25-4.85). Stratification of participants with DM2 by metformin use revealed no difference in risk between never (OR: 1.44, 95%CI: 0.78-2.67) and ever users (OR: 1.19, 95%CI: 0.72-1.99) relative to non-DM2 participants. PC risk also did not differ across groups of metformin or DM2 duration. In this clinic-based case-control study of PC, metformin use was not associated with PC risk. Specifically, our results suggest that metformin is neither associated with PC risk in those with DM2, nor does it attenuate or exacerbate PC risk associated with DM2. Citation Format: Evan J. Walker, Andrew H. Ko, Elizabeth A. Holly, Paige M. Bracci. Metformin use is not associated with pancreatic cancer risk in a clinic-based case-control study conducted in the San Francisco Bay Area, California. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2160. doi:10.1158/1538-7445.AM2014-2160

Metformin use among type 2 diabetics and risk of pancreatic cancer in a clinic-based case-control study.

A better understanding of the association between diabetes and pancreatic cancer (PC) may inform prevention and/or early detection strategies. Metformin has been associated with reduced risk of certain cancers, including PC, in some observational clinical studies. We assessed whether metformin use was associated with PC risk among those with type 2 diabetes (DM2), and whether metformin use modulated the association between DM2 and risk of PC. In total, 536 PC cases and 869 frequency-matched controls were recruited predominantly from University of California San Francisco medical clinics from 2006 to 2011. Eligible participants completed direct interviews using a structured risk factor questionnaire. The association between metformin use and PC risk was assessed using propensity score-weighted unconditional logistic regression methods in analyses restricted to diabetics and adjusted multivariable logistic models in the total study population. Ever use of metformin was not associated with PC risk in analyses restricted to DM2 (N = 170) participants (adjusted OR: 1.01, 95% CI: 0.61-1.68). In the total study population (N = 1,405) using nondiabetics as the referent group, PC risk was inversely associated with diabetes duration (ptrend < 0.001). Further, when DM2 participants were grouped by ever/never use of metformin and compared with nondiabetics, metformin use did not affect the association between DM2 and PC risk (never users: OR: 1.44, 95% CI: 0.78-2.67; ever users: OR: 1.19, 95% CI: 0.72-1.99). Results from our clinic-based case-control study suggest that metformin use is not associated with PC risk among those with DM2 and does not alter the association between DM2 and PC risk.

Clinical features and course of ocular toxocariasis in adults.

PurposeTo investigate the clinical features, clinical course of granuloma, serologic findings, treatment outcome, and probable infection sources in adult patients with ocular toxocariasis (OT).MethodsIn this retrospective cohort study, we examined 101 adult patients diagnosed clinically and serologically with OT. Serial fundus photographs and spectral domain optical coherence tomography images of all the patients were reviewed. A clinic-based case-control study on pet ownership, occupation, and raw meat ingestion history was performed to investigate the possible infection sources.ResultsAmong the patients diagnosed clinically and serologically with OT, 69.6% showed elevated immunoglobulin E (IgE) levels. Granuloma in OT involved all retinal layers and several vitreoretinal comorbidities were noted depending on the location of granuloma: posterior pole granuloma was associated with epiretinal membrane and retinal nerve fiber layer defects, whereas peripheral granuloma was associated with vitreous opacity. Intraocular migration of granuloma was observed in 15 of 93 patients (16.1%). Treatment with albendazole (400 mg twice a day for 2 weeks) and corticosteroids (oral prednisolone; 0.5–1 mg/kg/day) resulted in comparable outcomes to patients on corticosteroid monotherapy; however, the 6-month recurrence rate in patients treated with combined therapy (17.4%) was significantly lower than that in patients treated with corticosteroid monotherapy (54.5%, P = 0.045). Ingestion of raw cow liver (80.8%) or meat (71.2%) was significantly more common in OT patients than healthy controls.ConclusionsOur study discusses the diagnosis, treatment, and prevention strategies for OT. Evaluation of total IgE, in addition to anti-toxocara antibody, can assist in the serologic diagnosis of OT. Combined albendazole and corticosteroid therapy may reduce intraocular inflammation and recurrence. Migrating feature of granuloma is clinically important and may further suggest the diagnosis of OT. Clinicians need to carefully examine comorbid conditions for OT. OT may be associated with ingestion of uncooked meat, especially raw cow liver, in adult patients.

Statin use and risk of pancreatic cancer: Results from a large clinic-based case-control study.

4117 Background: Statins are cholesterol-lowering medications whose pleiotropic effects include alterations in growth signaling as well as immunomodulatory and anti-inflammatory effects that may al...

Case–control study of genus‐beta human papillomaviruses in plucked eyebrow hairs and cutaneous squamous cell carcinoma

Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous cell carcinoma (SCC). We conducted a clinic-based case-control study to investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load was determined in a subset of specimens positive for a single HPV type. Associations with SCC were estimated by odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and sex using logistic regression. Statistical tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls (73%) (p < 0.05), and the association with SCC increased with the number of HPV types present, (≥ 4 types vs. HPV-negative: OR = 2.02, 95% CI = 1.07-3.80; p(trend) = 0.02). Type-specific associations were observed between SCC and DNA in EBH for HPV23 (OR = 1.90, 95% CI = 1.10-3.30) and HPV38 (OR = 1.84, 95% CI = 1.04-3.24). Additionally, when compared with the controls, the DNA prevalence in EBH was significantly higher among cases for 11 of the 25 genus-beta types tested, when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50). Compared to controls, the mean viral DNA load in EBH among the selected cases was greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely than controls to have HPV DNA+ EBH for single and multiple HPV types, providing additional support for the potential role of genus-beta HPV infections in SCC development.

Meat-Related Mutagens and Pancreatic Cancer: Null Results from a Clinic-Based Case–Control Study

Pancreatic cancer is a devastating disease for which the role of dietary factors remains inconclusive. The study objective was to evaluate risk of pancreatic cancer associated with meat preparation methods and meat-related mutagen consumption using a clinic-based case-control design. There were 384 cases and 983 controls; subjects provided demographic information and completed a 144-item food frequency questionnaire, which was used to estimate meat mutagen intake using the National Cancer Institute's CHARRED database (Bethesda, MD). Logistic regression was used to calculate ORs and 95% confidence intervals (CI), adjusted for factors including age, sex, cigarette smoking, body mass index, and diabetes mellitus. Overall, the findings were null with respect to meat mutagen intake and pancreatic cancer. The results do not support an association between well-done meat or meat-related mutagen intake and pancreatic cancer and contrast with generally increased risks reported in previous studies. These data contribute to evidence about pancreatic cancer and potentially carcinogenic compounds in meat.

Case–Control Study of Cutaneous Human Papillomavirus Infection in Basal Cell Carcinoma of the Skin

Genus-β human papillomavirus (HPV) DNA has been detected in basal cell carcinoma (BCC) tumors, but most epidemiologic studies have not observed associations between genus-β HPV seropositivity and BCC. A clinic-based case-control study was conducted to investigate cutaneous HPV infection in BCC. BCC cases (n=224) were recruited from a dermatology clinic, and controls (n=300) were patients who were screened negative for skin cancer. Antibodies against cutaneous HPV types in genera α, β, γ, mu, and nu were measured, and tumors from a subset of BCC cases (n=195) were tested for HPV DNA. Overall associations were observed between BCC and seropositivity for HPV types in genus-α (odds ratio (OR)=1.61; 95% confidence interval (CI)=1.11-2.35), γ (OR=1.78; 95% CI=1.22-2.60), and mu (OR=1.56; 95% CI=1.06-2.30). BCC cases with β-HPV DNA in their tumors were more likely to be β-HPV seropositive than controls (OR=1.76; 95% CI=1.03-3.01), with type-specific associations observed for HPV8 and HPV23, whereas no association was observed between β-HPV seropositivity and β-HPV DNA-negative BCC. No concordance between seropositivity and tumor DNA status was observed for HPV types in genera α and γ. In conclusion, the combined serology and tumor DNA results suggest that β HPV types may have a role in BCC. Additional studies of BCC that assess HPV types in multiple genera are needed.

Abstract 104: Toenail iron, genetic variation in iron status, and the risk and outcome of glioma .

Abstract Elevated iron stores can trigger overproduction of reactive oxygen species and induce oxidative DNA damage. To our knowledge, no studies have investigated the association of body iron stores with the risk of glioma. In this investigation, we examined single nucleotide polymorphisms (SNPs) identified as markers of iron status in genome-wide association studies, and also measured iron stores in toenail samples in a clinic-based case-control study conducted at medical centers in the southeastern US. Genotyping was performed in 622 newly diagnosed, nonrecurrent glioma cases (including 341 WHO grade IV glioblastomas (GBM); 146 WHO grade II or III astrocytomas, 94 mixed oligoastrocytomas (MOAs) and oligodendrogliomas, and 41 gliomas with unspecified histology) and 628 healthy controls with no history of brain tumors. Illumina GoldenGate and Taqman OpenArray assays were used to genotype oral DNA samples. A total of 24 SNPs associated with markers of iron status were genotyped. Iron levels in toenail samples were measured in 200 glioma cases and 200 controls using neutron-activation analysis. Logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk according to examined genotypes and toenail iron levels. Proportional hazards regression was used to estimate age and gender-adjusted hazard ratios (HR) for glioma-related death among 320 patients with GBM or high grade astrocytomas all treated with the current standard of care for high grade glioma (eg. surgery, radiation and temozolomide) (248 deaths; median Kaplan-Meier survival: 15.0 months). We observed no overall association with glioma risk or patient outcome for SNPs in ARSB, BTN1A1, C7ORF10, FLJ43390, GHR, GTSCR1, HFE, HIST1H2BJ, KRT18P33, LRRC16, SCGN, SLC17A1, TOPBP1, and WTAP. Among non-GBM astrocytomas, borderline risk associations were observed for rs236918 in PCSK7 (G&amp;gt;C; minor allele frequency (MAF) = 0.11) (per variant allele OR = 0.50; 95% CI: 0.29 to 0.88; p for trend = 0.01) and with rs1049296 in TF (C&amp;gt;T; MAF = 0.17) (recessive model OR = 3.03; 95% CI: 1.11 to 8.27; p = 0.03). Among oligodendrogliomas/MOAs, risk associations were observed for rs4820268 in TMPRSS6 (A&amp;gt;G; MAF = 0.43) (recessive model OR = 1.91; 95% CI: 1.14 to 3.22; p = 0.01) and rs12216125 in TRIM38 (C&amp;gt;T; MAF = 0.35) (dominant model OR = 1.67; 95% CI: 1.03 to 2.72; p = 0.04). No SNPs were associated with the risk of GBM. One SNP, rs972275 in RSPO3 (G&amp;gt;C; MAF = 0.38), was associated with shorter patient survival (dominant model HR = 1.40; 95% CI: 1.06, 1.87; p=0.02). Increasing levels of toenail iron was associated with a non-significant decrease in glioma risk (OR = 0.88; 95% CI: 0.77 to 1.02; p = 0.08). Iron levels were not associated with survival. To our knowledge this is the first report suggesting that genetically determined variation in iron status may affect glioma risk and patient outcome. Further studies are needed to confirm these results. Citation Format: Gabriella M. Anic, Reid C. Thompson, L. Burton Nabors, Jeffrey J. Olson, Melissa H. Madden, James E. Browning, John D. Brockman, Peter A. Forsyth, Kathleen M. Egan. Toenail iron, genetic variation in iron status, and the risk and outcome of glioma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 104. doi:10.1158/1538-7445.AM2013-104

Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma

Background: Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Methods: Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Results: Melanoma patients had longer telomeres than controls (odds ratio (OR)=3.75; 95% confidence interval (CI): 2.02–6.94 for highest versus lowest tertile) (P for trend=<0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR=0.01; 95% CI: 0.00–0.05 for highest versus lowest tertile) (P for trend=<0.0001) and BCC (OR=0.10; 95% CI: 0.06–0.19 for highest versus lowest tertile) (P for trend=<0.0001). Conclusion: Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC.

Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma: A clinic-based case-control study

BackgroundAbnormal immune function is a key factor in predisposition to non-Hodgkin lymphoma (NHL). We evaluated the association of 30 cytokines individually and as a profile with diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. MethodsWe used a multiplexed assay to measure 30 cytokine concentrations in pre-treatment serum in a case-control study of 234 FL, 188 DLBCL, and 400 control participants. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex, and polytomous regression was used to evaluate heterogeneity between FL and DLBCL. Principal components analysis (PCA) was used to assess cytokine profiles associated with FL and DLBCL. ResultsIn single cytokine modeling, we found that 12 of the 30 circulating serum cytokines were significantly (P<0.05) associated with FL and/or DLBCL after accounting for multiple testing (q<0.05). Soluble IL-2R (sIL-2R) had the strongest association with both FL (OR=6.0 for highest versus lowest tertile, 95% CI 3.8–9.5; p-trend=1.8×10−21) and DLBCL (OR=7.6, 95% CI 4.5–13.1; p-trend=7.2×10−20). IL1RA and IL-12p40 also showed similar associations for DLBCL and FL. In contrast, HGF, MIG, and MIP-1α had a stronger association with DLBCL compared to FL, and IL-6, IL-8, IL-10, IFN-γ, IP-10, and VEGF were only statistically significantly associated with DLBCL after accounting for multiple testing. However, in PCA modeling, a cytokine profile based on sIL-2R, IL-1RA, MIG, IP-10, IL-8, and IL-12p40 explained most of the variability between controls and both FL and DLBCL. ConclusionsWe identified some cytokines unique to DLBCL, but overall cytokine associations were more similar than distinct for DLBCL and FL. While these data are limited by concerns of reverse causality, they do suggest cytokines and cytokine profiles that can be prioritized in future studies.

An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome

Experimental and epidemiological evidence shows a beneficial role of vitamin D in cancer. In vitro evidence is consistent with a similar protective function in glioma; however, no study has yet examined the potential role of vitamin D in glioma. We evaluated the association between common genetic variants in the vitamin D pathway and glioma risk and patient outcome in 622 newly diagnosed glioma cases and 628 healthy controls enrolled in a clinic-based case-control study. Subjects were genotyped for 7 candidate and tagging single nucleotide polymorphisms in the vitamin D receptor and 8 additional variants in NADSYN1, GC, CYP24A1, CYP2R1, and C10ORF88 linked in genome-wide association studies to serum concentrations of vitamin D. Unconditional logistic regression was used to estimate age- and gender-adjusted odds ratios and 95% confidence intervals for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 320 patients diagnosed with high-grade tumors. P values were uncorrected for multiple comparisons. Risk of astrocytic tumors was associated with variant alleles in rs3829251 (NADSYN1), rs10741657 (CYP2R1), rs2228570 (Fok1, VDR), and rs731236 (Taq1, VDR). No risk associations were found among oligodendroglial tumors. Survival associations were observed according to variant status for rs1544410 (Bsm1, VDR) and rs6013897 (CYP24A1). This exploratory analysis provides limited evidence of a role for genetic variation in vitamin D pathway genes with glioma risk and survival.

Abstract 2629: Common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome

Abstract Experimental and clinical evidence suggest that vitamin D protects against several types of cancer by promoting cell differentiation and apoptosis and by inhibiting cell proliferation and angiogenesis. In vitro evidence supports a similar protective function in glioma; however, no study has examined whether common genetic variants in the vitamin D pathway are related to glioma risk or patient outcome. We evaluated these potential associations in a clinic-based case-control study conducted at medical centers in the southeastern US. Genotyping was performed in 623 newly diagnosed (eg. nonrecurrent) glioma cases (including 343 WHO grade IV glioblastomas (GBM); 148 WHO grade II or III astrocytomas, 95 oligoastrocytomas and oligodendrogliomas, and 37 gliomas with unspecified histology) and 631 healthy controls with no history of brain tumors. A total of 7 candidate tagging single nucleotide polymorphisms (SNPs) were genotyped in the vitamin D receptor (VDR at 12q13) including rs2107301, rs2238135, rs4516035, rs731236 (Taq1), rs1544410 (Bsm1), rs11568820 (Cdx2), and rs2228570 (Fok1). SNPs associated with serum concentrations of 25-hydroxy vitamin D in genome-wide association studies (GWAS) were also evaluated including rs1155563, rs12512631, rs2282679, and rs7041 in GC (4q12-q13), rs10741657 in CYP2R1 (11p15), rs6013897 in CYP24A1 (20q13), rs3829251 in NADSYN1 (11q13), and rs6599638 at C10orf88 (10q26). Genotyping was performed in oral DNA samples using Illumina GoldenGate and Taqman OpenArray assays. Logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate age and gender-adjusted hazard ratios (HR) for glioma-related death among 439 patients with high grade tumors including GBM and high grade astrocytomas (331 deaths; median Kaplan-Meier survival: 15.0 months). GWAS SNPs in NADSYN1, GC, and C10ORF88 were not associated with glioma risk or patient survival. Risk associations limited to GBM were observed for rs2238135 in the VDR (G&amp;gt;C; minor allele frequency (MAF) = 0.20) (per variant allele OR = 1.31; 95% CI: 1.01 to 1.71; p for trend = 0.04) and for GWAS SNP rs10741657 located near CYP2R1 (G&amp;gt;A; MAF = 0.40) (per variant allele OR = 0.79; 95% CI: 0.63 to 0.98; p for trend = 0.03). The variant allele in CYP24A1 rs6013897 (T&amp;gt;A; MAF = 0.20) was associated with prolonged survival among patients with high grade tumors (per variant allele HR = 0.79; 95% CI: 0.59 to 0.97; p for trend = 0.03) in patients uniformly treated with the current standard of care (surgery, radiation and temozolomide). To our knowledge this is the first report suggesting that genetic variation in vitamin D related genes may be a determinant of glioma risk and outcome. Further studies are needed to confirm these results and identify the putative causal variant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2629. doi:1538-7445.AM2012-2629

The Effect of Alcohol use on IL-6 Responses Across Different Racial/Ethnic Groups

Chronic inflammation has become increasingly recognized as a health threat for people living with HIV, given its associations with multiple diseases. Accordingly, the scientific community has prioritized the need to identify mechanisms triggering inflammation. A clinic-based case-control study was designed to elucidate the plausible effects of alcohol use on IL-6. Peripheral blood mononuclear cells for measuring IL-6 culture supernatant and plasma for HIV assessments were collected from 59 hazardous alcohol users and 66 nonhazardous alcohol users, who were matched according to their age, gender and US CDC HIV severity status. Stimulated peripheral blood mononuclear cells produced significantly higher amounts of IL-6 in hazardous alcohol users compared with nonhazardous alcohol users. However, racial status and receiving HAART significantly moderated this effect. Notably, in both HAART and non-HAART scenarios, IL-6 levels were associated with CD4 counts and viral burden. A distinctive IL-6 production pattern across racial/ethnic groups was also evident and showed that, when prescribed HAART, Hispanic hazardous alcohol users have a particularly high risk of morbidity compared with their Caucasian and African-American counterparts. After adjusting for confounders (e.g., sociodemographics and HIV disease status), regression analyses confirmed that chronic inflammation, as indicated by IL-6 levels (log), is associated with alcohol use, race/ethnicity and thrombocytopenia, and tended to be related to concurrent smoking. Our data confirm that, despite HAART, people living with HIV still have a persistent inflammatory response that, in our study, was associated with chronic hazardous alcohol use. The data also highlight racial/ethnic disparities in IL-6 that justify further investigations.