Hendrickson, S. J., Lindstrom, S., Eliassen, A. H., Rosner, B. A., Chen, C., Barrdahl, M., Brinton, L., Buring, J., Canzian, F., Chanock, S., Clavel-Chapelon, F., Figueroa, J. D., Gapstur, S. M., Garcia-Closas, M., Gaudet, M. M., Haiman, C. A., Hazra, A., Henderson, B., Hoover, R., Husing, A., Johansson, M., Kaaks, R., Khaw, K. T., Kolonel, L. N., Le Marchand, L., Lissowska, J., Lund, E., McCullough, M. L., Peplonska, B., Riboli, E., Sacerdote, C., Sanchez, M. J., Tjonneland, A., Trichopoulos, D., van Gils, C. H., Yeager, M., Kraft, P., Hunter, D. J., Ziegler, R. G., Willett, W. C. (2013) Plasma Carotenoid- and Retinol-Weighted Multi-SNP Scores and Risk of Breast Cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 22 (5). pp. 927-936. ISSN 1055-9965

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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 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.

Item Type:	Article
Authors (ICR Faculty only):	Garcia-Closas, Montse
All Authors:	Hendrickson, S. J., Lindstrom, S., Eliassen, A. H., Rosner, B. A., Chen, C., Barrdahl, M., Brinton, L., Buring, J., Canzian, F., Chanock, S., Clavel-Chapelon, F., Figueroa, J. D., Gapstur, S. M., Garcia-Closas, M., Gaudet, M. M., Haiman, C. A., Hazra, A., Henderson, B., Hoover, R., Husing, A., Johansson, M., Kaaks, R., Khaw, K. T., Kolonel, L. N., Le Marchand, L., Lissowska, J., Lund, E., McCullough, M. L., Peplonska, B., Riboli, E., Sacerdote, C., Sanchez, M. J., Tjonneland, A., Trichopoulos, D., van Gils, C. H., Yeager, M., Kraft, P., Hunter, D. J., Ziegler, R. G., Willett, W. C.
Additional Information:	ISI Document Delivery No.: 143UR Times Cited: 0 Cited Reference Count: 29 Hendrickson, Sara J. Lindstroem, Sara Eliassen, A. Heather Rosner, Bernard A. Chen, Constance Barrdahl, Myrto Brinton, Louise Buring, Julie Canzian, Federico Chanock, Stephen Clavel-Chapelon, Francoise Figueroa, Jonine D. Gapstur, Susan M. Garcia-Closas, Montserrat Gaudet, Mia M. Haiman, Christopher A. Hazra, Aditi Henderson, Brian Hoover, Robert Husing, Anika Johansson, Mattias Kaaks, Rudolf Khaw, Kay-Tee Kolonel, Laurence N. Le Marchand, Loic Lissowska, Jolanta Lund, Eiliv McCullough, Marjorie L. Peplonska, Beata Riboli, Elio Sacerdote, Carlotta Sanchez, Maria-Jose Tjonneland, Anne Trichopoulos, Dimitrios van Gils, Carla H. Yeager, Meredith Kraft, Peter Hunter, David J. Ziegler, Regina G. Willett, Walter C. 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] This project was supported in part by the U.S. NIH, NCI (cooperative agreements U01-CA98233-07 to D.J. Hunter; U01-CA98710-06 to Michael J. Thun; U01-CA98216-06 to E. Riboli and R. Kaaks; and U01-CA98758-07 to B. Henderson) and Intramural Research Program of NIH and NCI, Division of Cancer Epidemiology and Genetics. This project was additionally supported in part by P01 CA87969, R01 CA131218, R01 CA49449, U01 CA098233, and R03 CA133937. The GWAS of breast cancer in NHS was supported by the NCI's Cancer Genetic Markers of Susceptibility Study (CGEMS). S.J. Hendrickson was supported in part by training grants NIH 5 T32 CA09001 and R25 CA098566. Amer assoc cancer research Philadelphia
Uncontrolled Keywords:	single nucleotide polymorphisms beta-carotene mendelian randomization vitamin-a pooled analysis lung-cancer disease enzymes 15,15-monooxygenase cleavage
Research teams:	Closed research groups > Molecular Epidemiology
Depositing User:	Alexander Smithson
Date Deposited:	24 Jun 2013 11:36
Last Modified:	01 Dec 2015 13:25
URI:	http://publications.icr.ac.uk/id/eprint/12524

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