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Genetic Variation Interacts with Selenium Exposure Regarding Breast Cancer Risk: Assessing Dietary Intake,Serum Levels and Genetically Elevated Selenium Levels
Authors:Malte Sandsveden  Ylva Bengtsson  Olle Melander  Ann H. Rosendahl  Jonas Manjer
Affiliation:1.Department of Clinical Sciences Malmö, Lund University, 20213 Malmö, Sweden; (Y.B.); (O.M.); (J.M.);2.Department of Surgery, Skåne University Hospital, 20501 Malmö, Sweden;3.Department of Internal Medicine, Skåne University Hospital, 20501 Malmö, Sweden;4.Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, 22184 Lund, Sweden;
Abstract:Selenium has been suggested to be protective regarding breast cancer risk but no overall effect has been established. Genetics may modify the effect. This study compares the effect of selenium exposure on breast cancer risk between women with different alleles in single-nucleotide polymorphisms (SNPs). The Malmö Cancer and Diet Study, a cohort including 17,035 women and >25 years of follow-up on breast cancer diagnosis, was used. Five promising SNPs regarding interaction with selenium exposure were selected from the literature: rs1050450, rs4880, rs3877899, rs7579, and rs71304. Selenium exposure was assessed in three ways: genetically elevated (n = 16,429), dietary intake (n = 15,891) and serum levels (n = 2037) at baseline. Cox regression and logistic regression analyses evaluated breast cancer risk from selenium exposure, stratified for the SNPs and adjusted for risk factors. A total of 1946 women were diagnosed with breast cancer. Women with T/T alleles in rs1050450 had lower breast cancer risk compared with C/C, HR 0.81 (0.68–0.96). Interaction by rs1050450 limited a protective effect of higher selenium intake to T/T carriers, HR 0.68 (0.43–1.08) for intermediate intake and HR 0.63 (0.40–1.00) for high intake. No interactions or risk differences were seen for other SNPs or for serum selenium or genetically elevated selenium. The results indicate that genetic variation in rs1050450 might affect breast cancer risk and that selenium exposure could be a possible modifiable risk factor for breast cancer among women with that variation.
Keywords:selenium   breast cancer   single-nucleotide polymorphisms   cohort
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