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Nonsynonymous single nucleotide polymorphisms in DNA damage repair pathways and lung cancer risk
Author(s) -
Tanaka Yugo,
Maniwa Yoshimasa,
Bermudez Vladimir P.,
Doi Takefumi,
Nishio Wataru,
Ohbayashi Chiho,
Okita Yutaka,
Hurwitz Jerard,
Hayashi Yoshitake,
Yoshimura Masahiro
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24850
Subject(s) - single nucleotide polymorphism , xrcc1 , heterozygote advantage , nonsynonymous substitution , odds ratio , lung cancer , medicine , cancer , oncology , genetics , biology , genotype , gene , genome
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. Cancer 2010. © 2010 American Cancer Society.