Lee Ga Young, Jang Jin-Sung, Lee Sin Yeob, Jeon Hyo-Sung, Kim Kyung Mee, Choi Jin Eun, Park Jung Min, Chae Myung Hwa, Lee Won Kee, Kam Sin, Kim In-San, Lee Jae-Tae, Jung Tae Hoon, Park Jae Yong
Cancer Research Institute, Kyungpook National University Hospital, Daegu, South Korea.
Int J Cancer. 2005 Jul 10;115(5):807-13. doi: 10.1002/ijc.20900.
Polymorphisms in DNA repair genes may be associated with differences in the capacity to repair DNA damage and thereby influence an individual's susceptibility to smoking-related cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (-449G-->C, -371G-->A, -27G-->C, Val499Arg, PAT-/+, IVS11-5C-->A and Lys939Gln) and their haplotypes with lung cancer risk in a Korean population. XPC genotypes were determined in 432 lung cancer patients and 432 healthy controls frequency-matched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined -27CG+CC genotype was associated with a significantly increased risk for overall lung cancer compared to the -27GG genotype (adjusted OR = 1.97, 95% CI 1.22-3.17, p = 0.005). The other 6 polymorphisms were not significantly associated with overall risk of lung cancer. When lung cancer cases were categorized by tumor histology, the -371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined -371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09-4.00, p = 0.03). The PAT-/+, IVS11-5C-->A and Lys939Gln polymorphisms were associated with a significantly decreased risk of small cell carcinoma (SM) under a dominant model for the polymorphic allele (adjusted OR = 0.49, 95% CI 0.29-0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36-1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35-0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11-5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37-0.85, p = 0.007 and Bonferroni-corrected p = 0.049), whereas haplotype 5 (1122111) containing the -27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41-5.87, p = 0.004 and Bonferroni-corrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer.
DNA修复基因中的多态性可能与DNA损伤修复能力的差异相关，从而影响个体对吸烟相关癌症的易感性。为了验证这一假设，我们在韩国人群中研究了7种XPC多态性（-449G→C、-371G→A、-27G→C、Val499Arg、PAT-/+、IVS11-5C→A和Lys939Gln）及其单倍型与肺癌风险的潜在关联。在432例肺癌患者和432例年龄及性别频率匹配的健康对照中确定了XPC基因型。使用Phase程序中的贝叶斯算法预测XPC单倍型。与-27GG基因型相比，-27CG + CC联合基因型与总体肺癌风险显著增加相关（调整后的OR = 1.97，95% CI 1.22 - 3.17，p = 0.005）。其他6种多态性与总体肺癌风险无显著关联。当按肿瘤组织学对肺癌病例进行分类时，与-371GG和GA联合基因型相比，-371AA基因型与鳞状细胞癌风险显著增加相关（调整后的OR = 2.08，95% CI 1.09 - 4.00，p = 0.03）。在多态性等位基因的显性模型下，PAT-/+、IVS11-5C→A和Lys939Gln多态性与小细胞癌（SM）风险显著降低相关（调整后的OR分别为0.49，95% CI 0.29 - 0.82，p = 0.006；调整后的OR = 0.60，95% CI 。36 - 1.00，p = 0.05；调整后的OR = 0.58，95% CI 0.35 - 0.97，p = 0.04）。与基因分型分析一致，包含PAT+/IVS11-5A/939Gln等位基因的单倍型4（1112222）与SM风险显著降低相关（调整后的OR = 0.56，95% CI 0.37 - 0.85，p = 0.007，经Bonferroni校正后p = 0.049），而包含-27C等位基因的单倍型5（1122111）与SM风险显著增加相关（调整后的OR = 2.88，95% CI 1.41 - 5.87，p = 0.004，经Bonferroni校正后p = 0.028）。这些结果表明，XPC多态性/单倍型可能有助于肺癌的遗传易感性。
