Nonsynonymous single nucleotide polymorphisms in DNA damage repair pathways and lung cancer risk.
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, POLdelta1 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 POLdelta1 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, POLdelta1 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.
Tanaka
Yugo
Y
Division of Thoracic Surgery, International Center for Medical Research and Treatment, Kobe, Japan.
Maniwa
Yoshimasa
Y
Bermudez
Vladimir P
VP
Doi
Takefumi
T
Nishio
Wataru
W
Ohbayashi
Chiho
C
Okita
Yutaka
Y
Hurwitz
Jerard
J
Hayashi
Yoshitake
Y
Yoshimura
Masahiro
M
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking