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More than 300 associations between genetic polymorphisms and approximately 70 common diseases have been identified in genome-wide association studies (review: Hindorff et al. 2009, http://www.genome.gov/gwastudies). The design of most studies included a discovery group where candidate variants were identified, which were then validated using several sets of follow-up groups. The majority of all identified variants are of moderate risk or the so-called wimp SNPs with odds ratios lower than 1.5. However, because of their high number and relatively high frequency, these wimp SNPs may collectively have a relevant impact on whether an individual develops a disease.
In recent years, polymorphisms and their association with disease and xenobiotic metabolism have also been a cutting-edge topic in our journal (Hanioka et al. 2010; Fuciarelli et al. 2009). Further examples include:
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The effect of UDP glucuronosyltransferase variants on bisphenol A glucuronidation (Hanioka et al. 2011)
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The association between GSTM1 and T1 polymorphisms and chromosomal aberrations (Santovito et al. 2011)
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The modulation of PAH metabolites in individuals exposed to bitumen (Rihs et al. 2011)
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The variability of arsenic metabolism (Fujihara et al. 2011)
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The association of XPD/ERCC2 polymorphisms with skin lesion prevalence (Lin et al. 2010)
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The association of hOGG1 with oxidative DNA damage (Ke et al. 2009)
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The modulation of prostate cancer risk by GSTM3 (Kesarwani et al. 2009)
However, significant progress has also been achieved in the field of urinary bladder cancer. Genome-wide association studies have identified eleven polymorphisms since 2008 that are associated with urinary bladder cancer risk (Rafnar et al. 2011; Rothman et al. 2010; Kiemeney et al. 2010; Selinski et al. 2011, 2012a, b; Lehmann et al. 2010; Golka et al. 2009). Therefore, the editors are pleased that Klaus Golka and colleagues from the IfADo Leibniz Research Centre in Dortmund, Germany, contributed a comprehensive state-of-the-art review on genetic variants in urinary bladder cancer (Golka et al. 2011). The main take-home messages of the article are:
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All newly discovered SNPs have odds ratios smaller than 1.5.
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Despite the low odds ratios, these “wimp SNPs” may nevertheless be relevant for the population attributable risk, because of their relative frequent occurrence.
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The functions of the affected genes comprise xenobiotic metabolism, cell cycle and apoptosis control, and DNA repair.
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Several newly discovered SNPs are far away from the coding regions and possibly represent distant-acting enhancers.
In addition to providing a comprehensive overview of the recently discovered and validated SNPs, the review also summarizes the 163 “old SNPs” that have been reported in relation to bladder cancer, but not yet consistently validated. The article comes highly recommended to those working in the field of polymorphisms and cancer risk.
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Stewart, J.D., Marchan, R. Polymorphisms hit the headlines. Arch Toxicol 86, 1799–1801 (2012). https://doi.org/10.1007/s00204-012-0973-5
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DOI: https://doi.org/10.1007/s00204-012-0973-5