Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study.
BACKGROUND
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.


CONCLUSIONS
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.
McCullough
Marjorie L
ML
Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Road NE, Atlanta, GA 30329, USA. marji.mccullough@cancer.org
Stevens
Victoria L
VL
Diver
William R
WR
Feigelson
Heather S
HS
Rodriguez
Carmen
C
Bostick
Robin M
RM
Thun
Michael J
MJ
Calle
Eugenia E
EE
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D004032:Diet; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012307:Risk Factors; D019914:Taq Polymerase / Q000235:genetics; D014807:Vitamin D / Q000378:metabolism*
D014807:Vitamin D; D019914:Taq Polymerase; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific