Plasma carotenoid- and retinol-weighted multi-snp scores and risk of breast cancer in the national cancer institute breast and prostate cancer cohort consortium

Sara J. Hendrickson, Sara Lindström, A. Heather Eliassen, Bernard A. Rosner, Constance Chen, Myrto Barrdahl, Louise Brinton, Julie Buring, Federico Canzian, Stephen Chanock, Francoise Clavel-Chapelon, Jonine D. Figueroa, Susan M. Gapstur, Montserrat Garcia-Closas, Mia M. Gaudet, Christopher A. Haiman, Aditi Hazra, Brian Henderson, Robert Hoover, Anika HüsingMattias Johansson, Rudolf Kaaks, Kay Tee Khaw, Laurence N. Kolonel, Loic Le Marchand, Jolanta Lissowska, Eiliv Lund, Marjorie L. McCullough, Beata Peplonska, Elio Riboli, Carlotta Sacerdote, María Jose Sanchez, Anne Tjønneland, Dimitrios Trichopoulos, Carla H. Van Gils, Meredith Yeager, Peter Kraft, David J. Hunter, Regina G. Ziegler, Walter C. Willett

Research output: Contribution to journalArticlepeer-review

Abstract

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 b-carotene 15,150-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 b-carotene, 1.08 (0.98-1.20) for a-carotene, 1.04 (0.94-1.16) for b-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. Cancer Epidemiol Biomarkers Prev; 22(5); 927-36.

Original languageEnglish (US)
Pages (from-to)927-936
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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