Vitamin D receptor polymorphisms and breast cancer risk in a high-incidence population: a pilot study.

BACKGROUND: Marin County, CA has very high incidence of breast cancer. Traditional risk factors, such as those included in the Gail model, do not effectively stratify breast cancer in this population. This retrospective case-control pilot study evaluates DNA from volunteers from a previous Marin County breast cancer epidemiology study. A polyfactorial risk model (OncoVue; InterGenetics Incorporated) that incorporates 22 polymorphisms in 19 genes and 5 clinical risk factors was used to stratify risk in Marin County women. STUDY DESIGN: DNA genotyping was performed on 164 Caucasian women diagnosed with primary breast cancer in Marin County from 1997 to 1999 and 174 age- and ethnicity-matched control subjects. Individual lifetime risks were determined using the polyfactorial risk model and genotype frequencies in women at elevated risk were compared with the overall genotypes. RESULTS: The vitamin D receptor VDR ApaI A2/A2 (rs7975232) homozygous polymorphism was present in high frequency in elevated-risk women. Sixty-four percent of elevated-risk women had the VDR Apa1 A2/A2 genotype compared with only 34% in the overall study, a statistically significant 1.9-fold difference (p = 0.0003). VDR Apa1 A2/a1 and a1/a1 genotypes were also present, but in lower frequencies. CONCLUSIONS: The high frequency of the VDR Apa1 A2/A2 homozygous polymorphism in women designated as elevated risk for breast cancer by the polyfactorial risk model might be related to the high incidence rates of breast cancer in Marin County, CA. Vitamin D supplementation could modify risk of breast cancer in this population.

Inverse association of antioxidant and phytoestrogen nutrient intake with adult glioma in the San Francisco Bay Area: a case-control study.

BACKGROUND: Increasing evidence from epidemiologic studies suggest that oxidative stress may play a role in adult glioma. In addition to dietary antioxidants, antioxidant and weak estrogenic properties of dietary phytoestrogens may attenuate oxidative stress. Our hypothesis is that long-term consumption of dietary antioxidants and phytoestrogens such as genistein, daidzein, biochanin A, formononetin, matairesinol, secoisolariciresinol and coumestrol, may reduce the risk of adult glioma. METHODS: Using unconditional logistic regression models, we compared quartiles of consumption for several specific antioxidants and phytoestrogens among 802 adult glioma cases and 846 controls from two study series from the San Francisco Bay Area Adult Glioma Study, 1991-2000, controlling for vitamin supplement usage, age, socioeconomic status, gender, ethnicity and total daily calories. For cases, dietary information was either self-reported or reported by a proxy. For controls, dietary information was self-reported. Gender- and series-specific quartiles of average daily nutrient intake, estimated from food-frequency questionnaires, were computed from controls. RESULTS: Significant p-values (trend test) were evaluated using significance levels of either 0.05 or 0.003 (the Bonferroni corrected significance level equivalent to 0.05 adjusting for 16 comparisons). For all cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.003), carotenoids (alpha- and beta-carotene combined, p < 0.05), daidzein (p = 0.003), matairesinol (p < 0.05), secoisolariciresinol (p < 0.003), and coumestrol (p < 0.003). For self-reported cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.05) and daidzein (p < 0.05). CONCLUSION: Our results support inverse associations of glioma with higher dietary antioxidant index and with higher intake of certain phytoestrogens, especially daidzein.

Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area.

We compare survival estimates for population-based glioma cases by using two diagnostic coding schemes, (1) the International Classification of Diseases, Oncology, second edition (ICD-O-2) as reported by the Surveillance, Epidemiology, and End Results (SEER) program and (2) central neuropathology review diagnosis based on the World Health Organization II classification. In addition, among review categories, we estimate survival in relation to several patient demographic and treatment factors. Eligible cases included adults residing in the San Francisco Bay SEER Area with newly diagnosed, histologically confirmed glioma during the years 1991-1994 and 1997-1999. The study group included participating subjects for whom subsequent central neuropathology review confirmed glioma. We determined treatments, vital status, and other factors by using registry, interview, medical record, and active follow-up data. Survival differences between anaplastic astrocytoma (AA) and astrocytoma were apparent from review diagnoses (median months of survival for AA, 13.0 [95% CI, 9.9-19.5], and astrocytoma, 101.3 [95% CI lower limit, 42.1; upper limit not yet reached]), but not with ICD-O-2 diagnoses reported by SEER (median months of survival for AA, 16.6 [95% CI, 12.0-20.7], and astrocytoma, not otherwise specified, 17.2 [95% CI, 10.6-71.6]). This finding emphasizes the need for improvements in coding for nonglioblastoma astrocytomas to provide better population survival estimates. When review diagnosis was used, younger age and resection (vs. biopsy) were statistically significant for all histology groups analyzed by multivariable Cox proportional hazard models. Additional statistically significant variables were as follows: among 517 glioblastoma patients, radiation treatment and being married; among 105 AA patients, inclusion of chemotherapy in the initial treatment; and among 106 patients with nonanaplastic oligodendroglial tumors, college education. Further consideration of impact of marital status, education, and other social factors in glioma survival may be warranted.

Case-control study of use of nonsteroidal antiinflammatory drugs and glioblastoma multiforme.

Evidence from epidemiologic and experimental studies suggests that use of nonsteroidal antiinflammatory drugs (NSAIDs) reduces risk of colon and breast cancer. The association between use of aspirin and other NSAIDs and risk of adult glioblastoma multiforme (GBM) was evaluated among 236 incident GBM cases and 401 population-based controls frequency-matched on age, gender, and ethnicity from the San Francisco Bay Area Adult Glioma Study. Cases (or proxies) and controls were interviewed in person between May 1997 and August 2000. Cases with self-reported GBM reported less use of at least 600 pills of all types of NSAIDs combined during the 10-year prediagnostic period than did controls (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.3, 0.8). Findings were consistent for aspirin (OR = 0.51, 95% CI: 0.3, 0.8), ibuprofen (OR = 0.41, 95% CI: 0.2, 0.8), and naproxen/other NSAIDs (OR = 0.34, 95% CI: 0.1, 0.8). GBM cases also reported less use of acetaminophen than did controls (OR = 0.51, 95% CI: 0.3, 1.0). Eliminating participants who initiated NSAID use within 2 years of diagnosis yielded similar results. These findings show an inverse association between NSAID use and GBM. Further studies are warranted to determine whether NSAIDs might be effective in the inhibition of GBM development or progression.