期刊
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
卷 22, 期 5, 页码 927-936出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-13-0017
关键词
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资金
- U.S. NIH, NCI [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]
- NIH
- NCI, Division of Cancer Epidemiology and Genetics
- NCI's Cancer Genetic Markers of Susceptibility Study (CGEMS)
- [P01 CA87969]
- [R01 CA131218]
- [R01 CA49449]
- [U01 CA098233]
- [R03 CA133937]
- [NIH 5 T32 CA09001]
- [R25 CA098566]
- Cancer Research UK [14136] Funding Source: researchfish
- Medical Research Council [G1000143, G0401527] Funding Source: researchfish
Background: Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in beta-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. Methods: We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. Results: Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk [OR (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores = 1.04 (0.94-1.16) for beta-carotene, 1.08 (0.98-1.20) for alpha-carotene, 1.04 (0.94-1.16) for beta-cryptoxanthin, 0.95 (0.87-1.05) for lutein/zeaxanthin, and 0.92 (0.83-1.02) for retinol]. Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. Conclusions: Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. Impact: Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer. (C) 2013 AACR.
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