Nonsynonymous single nucleotide polymorphisms in DNA damage repair pathways and lung cancer risk Journal Article
| Authors: | Tanaka, Y.; Maniwa, Y.; Bermudez, V. P.; Doi, T.; Nishio, W.; Ohbayashi, C.; Okita, Y.; Hurwitz, J.; Hayashi, Y.; Yoshimura, M. |
| Article Title: | Nonsynonymous single nucleotide polymorphisms in DNA damage repair pathways and lung cancer risk |
| Abstract: | BACKGROUND: Several reports have revealed the association between single nucleotide polymorphisms (SNPs) and the development of cancer. Although many SNPs have been investigated, they were tested individually. In this study, nonsynonymous SNPs present in DNA damage response genes were comprehensively analyzed for lung cancer susceptibility. METHODS: The authors selected 37 nonsynonymous SNPs in 23 genes involved in DNA damage repair pathways. Fifty lung adenocarcinoma patients resected at their institution between 2002 and 2005 and 50 individuals without any known history of cancer were recruited for a case-control study. RESULTS: Three variants (XRCC1 194Trp homozygotes, POLδ1 119His homozygotes, and RAD9 239Arg heterozygotes) tended to coassociate with lung cancer risk. The authors analyzed and calculated whether the association between combinations of these 3 SNPs significantly affected the risk of lung cancer. Compared with carriers of either XRCC1 194Trp homozygote or RAD9 239Arg heterozygote variants, noncarriers were at a significantly decreased risk for lung cancer (odds ratio [OR], 0.282; confidence interval [CI], 0.089-0.893). The same results were found for the combination of POLδ1 119His homozygotes and RAD9 239Arg heterozygotes (OR, 0.277; CI, 0.077-0.993). Moreover, compared with carriers that had at least 1 of the 3 variants, noncarriers showed a more significant decrease in risk (OR, 0.263; CI, 0.090-0.767). CONCLUSIONS: Analysis of the presence of XRCC1 194Trp homozygote, POLδ1 119His homozygote, and RAD9 239Arg heterozygote variants revealed that their coassociation leads to a significant risk for the development of lung adenocarcinoma. Inclusive analyses of different SNPs were important in this cancer risk study. © 2010 American Cancer Society. |
| Keywords: | clinical article; controlled study; human tissue; aged; single nucleotide polymorphism; polymorphism, single nucleotide; cancer risk; adenocarcinoma; dna repair; cancer susceptibility; genetic predisposition to disease; lung neoplasms; gene frequency; lung cancer; smoking; heterozygote; risk; lung adenocarcinoma; genetic susceptibility; homozygote; dna breaks, double-stranded; arginine; histidine; protein rad9; tryptophan; rad9; dna damage repair pathway; minor allele frequency; nonsynonymous single nucleotide polymorphism; polδ1; polyphen; xrcc1; dna directed dna polymerase gamma; xrcc1 protein |
| Journal Title: | Cancer |
| Volume: | 116 |
| Issue: | 4 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2010-02-15 |
| Start Page: | 896 |
| End Page: | 902 |
| Language: | English |
| DOI: | 10.1002/cncr.24850 |
| PUBMED: | 20052722 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: CANCA" - "Source: Scopus" |
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