• 2019-07
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  • 2020-08
  • 2021-03
  • Selenoprotein P SePP is the major plasma


    Selenoprotein P (SePP) is the major Thonzonium Bromide selenoprotein with both transport and antioxidant functions [17]. Two functional SNPs in SePP, rs7579 and rs3877899, have been shown to influence levels of SePP isoforms in plasma as well as risk of colorectal cancer [50]. However, in the present study, neither rs3877899 nor a SNP in high LD with rs7579 (rs7717985; LD = 0.94) was associated with glioma risk in either the case-control or cohort study analysis. The present study had a number of strengths and limitations. The case-control study was based on subjects residing in the southeastern US including the state of FL where soil Se is relatively low compared to other regions of the US [51] thus potentially increasing range of toenail Se in participants and our ability to detect associations contrasting extreme levels of exposure. The study of genetic association in selenoenzyme pathway variants was based on a large case-control study for a rare tumor and we were able to attempt to validate associations in an independent prospective cohort study in which genotyping of subjects was performed based on the identical array. Glioma cases were rapidly ascertained and enrolled, generally within 2 months of diagnosis and, as toenail Se reflects dietary intake 6–12 months in the past [34], Se measures in most cases would have predated changes in diet that occurred from the disease or its treatment. Within the 300 cases studied, we found no correlation between toenail Se concentrations and the number of days between diagnosis and toenail collection (Pearson r = 0.03; p = 0.65), which ranged from to 88 days; hence, any delay to nail collection in cases would not have affected results. On the Thonzonium Bromide other hand, if there is a long latency to glioma diagnosis, Se measured in toenail samples may not have reflected exposure during an etiologically relevant timeframe in glioma. In addition, the sample size for toenail Se analyses was relatively limited (300 cases and 300 controls) and we lacked power to evaluate associations by glioma subtype or according to exposures like smoking or obesity associated with oxidative stress that may increase Se requirements [[52], [53], [54]]. Se levels vary by demographic and lifestyle factors [53] and low response rates in controls could potentially have biased selenium associations. Finally, previous studies show that selenium is efficiently retained in the brain even in conditions of Se deficiency [19]; hence, it possible that only severe Se depletion not typically encountered in the US has an impact on brain tumor development.
    Authorship contributions
    Funding The research was supported by the National Institutes of Health [grant number R01 CA116174 and R03 CA171612]. The work is based in part on the UK Biobank Resource under application number 16944.
    Introduction Remarkable progress has been made in the treatment of childhood cancer and survival rates have improved as a result of multimodal and risk adapted treatment strategies [1,2]. The etiology of childhood cancer remains largely unknown. However, it is estimated that approximately 5–10% of all cases can be attributed to genetic susceptibility [[3], [4], [5], [6], [7]]. Importantly, the genetic contribution to childhood cancer may have been underestimated due to lack of recognition of many hereditary cancer susceptibility syndromes (HCSS) or the under-reporting of family history [8,9]. Study of survivors of childhood cancer suggests that 29% of children were at risk for hereditary cancer based on patient’s cancer history, family history or presence of unique physical findings [9]. Thus, identifying patients with HCSS is crucial to ensure early diagnosis, identify need for genetic counselling, initiate cancer surveillance, reduce cancer morbidity and optimise treatment outcomes and cure [10,11].