title: Plasma carotenoid- and retinol-weighted multi-SNP scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
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 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Hendrickson
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.forename: A Heather
authors.initials: AH
authors.lastname: Eliassen
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: Myrto
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authors.lastname: Barrdahl
authors.forename: Louise
authors.initials: L
authors.lastname: Brinton
authors.forename: Julie
authors.initials: J
authors.lastname: Buring
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.forename: Montserrat
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authors.lastname: Garcia-Closas
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Aditi
authors.initials: A
authors.lastname: Hazra
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
authors.forename: Robert
authors.initials: R
authors.lastname: Hoover
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.forename: Mattias
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authors.lastname: Johansson
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Marjorie L
authors.initials: ML
authors.lastname: McCullough
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
mesh_terms: D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics; D002338:Carotenoids / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014801:Vitamin A / Q000097:blood* / Q000235:genetics; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D014801:Vitamin A; D002338:Carotenoids; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase