ABSTRACT
INTRODUCTION: Vitamin D receptor (VDR) polymorphisms have been inconsistently associated with breast cancer risk. Whether risk is influenced by polymorphisms in other vitamin D metabolism genes and whether calcium or vitamin D intake modifies risk by genotype have not been evaluated. METHODS: We conducted a nested case-control study within the Cancer Prevention Study II Nutrition Cohort of associations between breast cancer and four VDR single-nucleotide polymorphisms (SNPs), Bsm1,Apa1,Taq1, and Fok1, a poly(A) microsatellite, and associated haplotypes (baTL and BAtS). We also examined one SNP in the 24-hydroxylase gene (CYP24A1) and two in the vitamin D-binding protein (group-specific component [GC]) gene. Participants completed a questionnaire on diet and medical history at baseline in 1992. This study includes 500 postmenopausal breast cancer cases and 500 controls matched by age, race/ethnicity, and date of blood collection. RESULTS: Incident breast cancer was not associated with any genotype examined. However, women with the Bsm1 bb SNP who consumed greater than the median intake of total calcium (> or = 902 mg/day) had lower odds of breast cancer compared to women with the Bb or BB genotype and less than the median calcium intake (odds ratio 0.61, 95% confidence interval 0.38 to 0.96; p(interaction) = 0.01). Similar interactions were observed for Taq1 (T allele) and the poly(A) (LL) repeat. CONCLUSION: We found no overall association between selected vitamin D pathway genes and postmenopausal breast cancer risk. However, certain VDR gene polymorphisms were associated with lower risk in women consuming high levels of calcium, suggesting that dietary factors may modify associations by VDR genotype.
Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Diet , Polymorphism, Genetic , Vitamin D/metabolism , Adult , Aged , Case-Control Studies , Deoxyribonucleases, Type II Site-Specific/genetics , Female , Genotype , Humans , Middle Aged , Polymorphism, Single Nucleotide , Postmenopause , Risk Factors , Taq Polymerase/geneticsABSTRACT
OBJECTIVE: We examined the relation between whole grains, fruit, vegetables and dietary fiber and colon cancer risk in the prospective Cancer Prevention Study II Nutrition Cohort. METHODS: In 1992-1993, 62,609 men and 70,554 women completed questionnaires on medical history, diet and lifestyle behaviors. After exclusions, we confirmed 298 cases of incident colon cancer among men and 210 among women through August 31, 1997. RESULTS: Multivariate rate ratios (RR) and 95% confidence intervals (CI) for all dietary factors were null. However, a statistically non-significant 30% reduction in risk was observed for men with the highest vegetable intakes (RR = 0.69, CI = 0.47-1.03, top versus bottom quintile, p trend = 0.10). Men with very low (lowest tertile within the lowest quintile) intakes of vegetables and dietary fiber were at increased risk compared to those in the highest four quintiles of intake (vegetables RR = 1.79, CI = 1.22-2.61, p trend = 0.04, and fiber RR = 1.96, CI = 1.24-3.10, p trend = 0.006). Women with very low intakes of fruit were also at increased risk (RR = 1.86, CI = 1.18-2.94, p trend = 0.06). CONCLUSIONS: Higher intakes of plant foods or fiber were not related to lower risk of colon cancer. However, our data suggest that very low intakes of plant foods may increase risk, and that certain phytochemical subgroups may decrease risk.
