期刊
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
卷 19, 期 7, 页码 1812-1821出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-10-0151
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资金
- National Cancer Institute, National Institutes of Health [CA-95-011]
- Australasian Colorectal Cancer Family Registry [U01 CA097735]
- USC Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]
- Mayo Clinic [U01 CA074800]
- Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]
- Seattle Colorectal Cancer Family Registry [U01 CA074794]
- University of Hawaii Colorectal Cancer Family Registry [U01 CA074806]
- NCI [R01 CA112237, T32 CA009142, PO1 CA41108, CA-23074, CA 956060]
- National Cancer Institute of Canada
Background: Folate-associated one-carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer. Methods: This study utilized data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry. We used a comprehensive haplotype tagging single nucleotide polymorphism (tagSNP) approach to select 395 tagSNPs in 15 genes involved in folate and vitamin B-12 metabolism. Genotyping was done using the Illumina GoldenGate or Sequenom platforms. Risk factor and dietary data were collected using self-completed questionnaires. Microsatellite instability (MSI) status was determined using standard techniques, and tumor subsite was obtained from pathology reports. The association between SNPs and colorectal cancer was assessed using conditional logistic regression with sibships as the matching factor and assuming a log additive or codominant model. Results: In the log additive model, two linked (r(2) = 0.99) tagSNPs in the DHFR gene (rs1677693 and rs1643659) were associated with a significant decrease in colorectal cancer risk after correction for multiple testing (odds ratio, 0.87; 95% confidence interval, 0.71-0.94; P = 0.029; and odds ratio, 0.87; 95% confidence interval, 0.71-0.95; P = 0.034 for rs1677693 and rs1643659, respectively). These two linked (r(2) = 0.99) tagSNPs and one tagSNP in the MTR gene (rs4659744) were significantly associated with reduced colorectal cancer risk only among individuals not using multivitamin supplements. Conclusions: Overall, we found only moderate evidence that genetic variation in 15 folate pathway genes may affect colorectal cancer risk except in non-multivitamin users. Impact: This study suggests that multivitamin supplement use may modify the association between folate pathway genes and colorectal cancer risk in a post-folic-acid-supplemented population. Cancer Epidemiol Biomarkers Prev; 19(7); 1812-21. (C) 2010 AACR.
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