Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI

Supplement use during an intergroup clinical trial for breast cancer (S0221)

The use of supplements during chemotherapy is controversial, partly due to the potential effect of antioxidants on reduced efficacy of chemotherapy-related cytotoxicity. We examined supplement use among breast cancer patients registered to a clinical trial (SWOG 0221) before diagnosis and during treatment. Patients (n = 1,467) completed questionnaires regarding multivitamin and supplement use at trial registration (baseline) to capture use before diagnosis. Of these patients, 1,249 completed a 6-month followup questionnaire to capture use during treatment. We examined the use of vitamins C, D, E, B6, B12, folic acid, and calcium at these timepoints, as well as physician recommendations regarding supplement use. The use of vitamins C, E, folic acid, and calcium decreased during treatment, while the use of vitamin B6 increased. Five hundred seventy four patients (51 %) received no physician recommendations regarding supplement use. Among the remaining 49, 10 % were advised not to take multivitamins and/or supplements, 7 % were advised to use only multivitamins, and 32 % received recommendations to use multivitamins and/or supplements. Among patients who took vitamin C before diagnosis, those who were advised not to take supplements were >5 times more likely not to use of vitamin C during treatment than those not advised to stop use (OR = 5.27, 95 % CI 1.13–24.6). Previous non-users who were advised to take a multivitamin were nearly 5 times more likely to use multivitamins during treatment compared to those who received no recommendation (OR = 4.66, 95 % CI 2.10–10.3). In this clinical trial for high-risk breast cancer, supplement use generally decreased during treatment. Upon followup from the clinical trial, findings regarding supplement use and survival outcomes will better inform physician recommendations for patients on adjuvant chemotherapy

Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study

Introduction\ud American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics.\ud \ud Methods\ud In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.\ud \ud Results\ud More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs.\ud \ud Conclusions\ud These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women