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.
Highlights
Due to its significant role in antioxidation, the essential mineral selenium has been of interest to study in cancer development, including breast cancer [1]
Women who had a first-time breast cancer diagnosis during the cohort follow-up were younger than women without breast cancer and were less likely to have children but had a higher alcohol intake and were more likely to be non-manual workers and more likely to have used oral contraceptives, but were less likely to use hormone replacement therapy at baseline
glutathione peroxidase-1 (GPX-1) is selenium associated with previously been reported for this cohort, and we found no further interactions with the decreased risk of breast cancer for T/T carriers, and modifies the effect of dietary selenium other four
Summary
Due to its significant role in antioxidation, the essential mineral selenium has been of interest to study in cancer development, including breast cancer [1]. Current evidence does not support a general association between selenium levels and breast cancer risk, individual studies have found an inverse relationship [2–4]. Evidence suggests that the effect of genetic variation through single-nucleotide polymorphisms (SNPs) in selenium-associated genes needs to be considered [5,6]. Selenium mainly exerts its biological effect through selenoproteins, a group of 25 human proteins exclusively incorporating the selenium-containing amino acid selenocysteine [7]. The activity of selenoproteins is affected by selenium status [9]. The antioxidant function of selenoproteins has been suggested as the probable mechanism involved in the association of selenium and cancer development [8]
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