國家衛生研究院 NHRI:Item 3990099045/8759
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    题名: The roles of genetic polymorphisms for susceptibility of colorectal cancer in Chinese lynch syndrome families
    作者: Yeh, CC;Tang, RP;Chien, HT;Lai, CH;Chiu, LL;Lo, TP;Hung, KY;Wang, CY;You, JF;Hsiung, CA;Hsieh, LL
    贡献者: Division of Biostatistics and Bioinformatics
    摘要: Background: Lynch syndrome is associated with germ-line mutations in DNA mismatch repair (MMR) genes. Polymorphisms in candidate genes that have been implicated in sporadic colorectal cancer (CRC) risk may also play roles in hereditary CRC risk. In this retrospective analysis, we examined multiple polymorphisms (including MSH2 IVS10+12A>G, MLH1 A-93G, NAT1, GSTM1, GSTP1 Iel105Val, GSTA1 C-69T, TP53 Arg72Pro, CYP17A1 T-34C, CYP1A1*2C, CYP1A1*1F, TGFBR1 IVS7+24G>A, and TGFBR2 G-875A) to assess the genetic effect on the CRC risk in MLH1 and MSH2 mutation carriers. Material and Methods: DNA samples from 284 mutation-positive Lynch syndrome participants were genotyped by Sequenom iPLEX MassArray. Univariate and multivariate analysis was used to analyze the association between the genetic polymorphisms and CRC risk. Results: We found significant associations between the presence of variant alleles in TP53 Arg72Pro (G>C) and TGFBR2 G-875A genes and the risk of developing CRC among MLH1 and MSH2 mutation carriers. The TP53 Arg72Pro GC+CC genotypes were associated with decreased risk of CRC (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.42-0.94). However, the TGFBR2 G-875A GA+AA genotypes were associated with increased risk of CRC (HR = 1.60, 95% CI = 1.06-2.42). None of the other gene polymorphisms examined were associated with CRC risk. Conclusion: To our best knowledge, our study is the first and largest study investigating multiple genetic modifiers that may influence CRC risk in Chinese Lynch syndrome families. Our results suggested that TP53 and TGFBR2 polymorphisms may associate with CRC risk among MLH1 and MSH2 mutation carriers. Such knowledge may be helpful in identifying high-risk individuals who require more intensive surveillance.
    日期: 2014-10
    關聯: Cancer Research. 2014 Oct;74(19 Suppl.):Abstract No. LB-295.
    Link to: http://dx.doi.org/10.1158/1538-7445.am2014-lb-295
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000349910205328
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