Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk

Tokuki Sakiyama, Takashi Kohno, Sachiyo Mimaki, Tsutomu Ohta, Noriko Yanagitani, Tomotaka Sobue, Hideo Kunitoh, Ryusei Saito, Kimiko Shimizu, Chie Hirama, Junko Kimura, Go Maeno, Hiroshi Hirose, Takashi Eguchi, Daizo Saito, Misao Ohki, Jun Yokota

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126 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)730-737
Number of pages8
JournalInternational Journal of Cancer
Volume114
Issue number5
DOIs
Publication statusPublished - 2005 May 1

Keywords

  • DNA repair gene
  • Lung cancer
  • Par 2
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sakiyama, T., Kohno, T., Mimaki, S., Ohta, T., Yanagitani, N., Sobue, T., Kunitoh, H., Saito, R., Shimizu, K., Hirama, C., Kimura, J., Maeno, G., Hirose, H., Eguchi, T., Saito, D., Ohki, M., & Yokota, J. (2005). Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk. International Journal of Cancer, 114(5), 730-737. https://doi.org/10.1002/ijc.20790