Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk
| Autor: | Noriko Yanagitani, Go Maeno, Hiroshi Hirose, Chie Hirama, Ryusei Saito, Tomotaka Sobue, Takashi Kohno, Hideo Kunitoh, Daizo Saito, Jun Yokota, Tokuki Sakiyama, Kimiko Shimizu, Takashi Eguchi, Junko Kimura, Misao Ohki, Sachiyo Mimaki, Tsutomu Ohta |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cancer Research Lung Neoplasms DNA Ligases DNA Repair Genotype DNA repair DNA polymerase Single-nucleotide polymorphism Adenocarcinoma DNA Ligase ATP Risk Factors medicine Odds Ratio Humans Genetic Predisposition to Disease Amino Acids Gene Alleles Aged Aged 80 and over Genome Polymorphism Genetic biology Homozygote Smoking Nuclear Proteins Sequence Analysis DNA Middle Aged medicine.disease DNA Polymerase I Genes p53 Lung cancer susceptibility Nucleotidyltransferases Oncology Case-Control Studies Cancer research biology.protein Carcinoma Squamous Cell REV1 Female DNA Damage |
| Zdroj: | International journal of cancer. 114(5) |
| ISSN: | 0020-7136 |
| Popis: | 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. © 2004 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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