Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer

被引:174
作者
Popanda, O [1 ]
Schattenberg, T
Phong, CT
Butkiewicz, D
Risch, A
Edler, L
Kayser, K
Dienemann, H
Schulz, V
Drings, P
Bartsch, H
Schmezer, P
机构
[1] German Canc Res Ctr, DKFZ, Div Toxicol & Canc Risk Factors, D-6900 Heidelberg, Germany
[2] M Sklodowska Curie Mem Inst, Ctr Oncol, Dept Tumor Biol, Gliwice, Poland
[3] German Canc Res Ctr, DKFZ, Div Biostat, D-6900 Heidelberg, Germany
[4] Thoraxklin Heidelberg Rohrbach, Heidelberg, Germany
关键词
D O I
10.1093/carcin/bgh264
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Several polymorphisms in DNA repair genes have been reported to be associated with lung cancer risk including XPA (-4G/A), XPD (Lys751Gln and Asp312Asn), XRCC1 (Arg399Gln), APE1 (Asp148Glu) and XRCC3 (Thr241Met). As there is little information on the combined effects of these variants, polymorphisms were analyzed in a case-control study including 463 lung cancer cases [among them 204 adenocarcinoma and 212 squamous cell carcinoma (SCC)] and 460 tumor-free hospital controls. Odds ratios (OR) adjusted for age, gender, smoking and occupational exposure were calculated for the variants alone and combinations thereof. For homozygous individuals carrying the Glu variant of APE1, a protective effect was found (OR = 0.77, CI = 0.51-1.16). Individuals homozygous for the variants XPA (-4A) (OR = 1.53, CI = 0.94-2.5), XPD 751Gln (OR = 1.39, CI = 0.90-2.14) or XRCC3 241Met (OR = 1.29, CI = 0.85-1.98) showed a slightly higher risk for lung cancer overall. In the subgroup of adenocarcinoma cases, adjusted ORs were increased for individuals homozygous for XPA (-4A) (OR = 1.62, CI = 0.91-2.88) and XRCC3 241Met (OR = 1.65; CI = 0.99-2.75). When analyzing the combined effects of variant alleles, 54 patients and controls were identified that were homozygous for two or three of the potential risk alleles [i.e. the variants in nucleotide excision repair, XPA (-4A) and XPD 751Gln, and in homologous recombination, XRCC3-241Met]. ORs were significantly increased when all patients (OR = 2.37; CI = 1.26-4.48), patients with SCC (OR = 2.83; CI = 1.17-6.85) and with adenocarcinoma (OR = 3.05; CI = 1.49-6.23) were analyzed. Combinations of polymorphisms in genes involved in the same repair pathway (XPA + XPD or XRCC1 + APE1) affected lung cancer risk only in patients with SCC. These results indicate that lung cancer risk is only moderately increased by single DNA repair gene variants investigated but it is considerably enhanced by specific combinations of variant alleles. Analyses of additional DNA repair gene interactions in larger population-based studies are warranted for identification of high-risk subjects.
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页码:2433 / 2441
页数:9
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