title: Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk.
abstract: Single nucleotide polymorphisms (SNPs) were searched for in 36 genes involved in diverse DNA repair pathways, and 50 nonsynonymous (associated with amino acid changes) SNPs identified were assessed for associations with lung cancer risk by a case-control study consisting of 752 adenocarcinoma cases, 250 squamous cell carcinoma cases and 685 controls. An SNP, Arg72Pro, of the TP53 gene encoding a DNA damage response protein showed the strongest association with squamous cell carcinoma risk (OR Pro/Pro vs. Arg/Arg = 2.2), while 2 other SNPs, Phe257Ser of the REV gene encoding a translesion DNA polymerase and Ile658Val of the LIG4 gene encoding a DNA double-strand break repair protein, also showed associations (OR Ser/Ser vs. Phe/Phe = 2.0 and OR Ile/Val vs. Ile/Ile = 0.4, respectively). An SNP, Thr706Ala, in the POLI gene encoding another translesion DNA polymerase was associated with adenocarcinoma and squamous cell carcinoma risk, particularly in individuals of ages < 61 years (OR Ala/Ala + Ala/Thr vs. Thr/Thr = 1.5 and 2.4, respectively). POLI is the human counterpart of PolI, a strong candidate for the Par2 (pulmonary adenoma resistance 2) gene responsible for adenoma/adenocarcinoma susceptibility in mice. The present results suggest that these 4 SNPs function as genetic factors underlying lung cancer susceptibility by modulating activities to maintain the genome integrity of each individual.
authors.affiliation: Center for Medical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Tokuki
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Mimaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ohta
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanagitani
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Sobue
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Ryusei
authors.initials: R
authors.lastname: Saito
authors.forename: Kimiko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Chie
authors.initials: C
authors.lastname: Hirama
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.forename: Go
authors.initials: G
authors.lastname: Maeno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirose
authors.forename: Takashi
authors.initials: T
authors.lastname: Eguchi
authors.forename: Daizo
authors.initials: D
authors.lastname: Saito
authors.forename: Misao
authors.initials: M
authors.lastname: Ohki
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000596:Amino Acids / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics*; D004256:DNA Polymerase I / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D016678:Genome; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012907:Smoking; D000099270:Y-Family DNA Polymerases
chemical_list: D000596:Amino Acids; D000072481:DNA Ligase ATP; D011088:DNA Ligases; D004256:DNA Polymerase I; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; C000607893:LIG4 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases