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 β-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 β-carotene, 1.08 (0.98-1.20) for α-carotene, 1.04 (0.94-1.16) for β-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.
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 β-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 β-carotene, 1.08 (0.98-1.20) for α-carotene, 1.04 (0.94-1.16) for β-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.
Authors: D J Hunter; E Riboli; C A Haiman; D Albanes; D Altshuler; S J Chanock; R B Haynes; B E Henderson; R Kaaks; D O Stram; G Thomas; M J Thun; H Blanché; J E Buring; N P Burtt; E E Calle; H Cann; F Canzian; Y C Chen; G A Colditz; D G Cox; A M Dunning; H S Feigelson; M L Freedman; J M Gaziano; E Giovannucci; S E Hankinson; J N Hirschhorn; R N Hoover; T Key; L N Kolonel; P Kraft; L Le Marchand; S Liu; J Ma; S Melnick; P Pharaoh; M C Pike; C Rodriguez; V W Setiawan; M J Stampfer; E Trapido; R Travis; J Virtamo; S Wacholder; W C Willett Journal: Nat Rev Cancer Date: 2005-12 Impact factor: 60.716
Authors: S Zhang; D J Hunter; M R Forman; B A Rosner; F E Speizer; G A Colditz; J E Manson; S E Hankinson; W C Willett Journal: J Natl Cancer Inst Date: 1999-03-17 Impact factor: 13.506
Authors: Sara J Hendrickson; Aditi Hazra; Constance Chen; A Heather Eliassen; Peter Kraft; Bernard A Rosner; Walter C Willett Journal: Am J Clin Nutr Date: 2012-11-07 Impact factor: 7.045
Authors: Julia S Sisti; Sara Lindström; Peter Kraft; Rulla M Tamimi; Bernard A Rosner; Tianying Wu; Walter C Willett; A Heather Eliassen Journal: Breast Cancer Res Treat Date: 2015-04-28 Impact factor: 4.872
Authors: Joshua W Smith; Nikki A Ford; Jennifer M Thomas-Ahner; Nancy E Moran; Eric C Bolton; Matthew A Wallig; Steven K Clinton; John W Erdman Journal: Am J Physiol Regul Integr Comp Physiol Date: 2016-09-14 Impact factor: 3.619