Jung Chi Young, Choi Jin Eun, Park Jung Min, Chae Myung Hwa, Kang Hyo-Gyoung, Kim Kyung Mee, Lee Su Jeong, Lee Won Kee, Kam Sin, Cha Seung Ick, Kim Chang Ho, Han Sung Beom, Jung Tae Hoon, Jeon Su Han, Park Jae Yong
Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):762-8. doi: 10.1158/1055-9965.EPI-05-0834.
Polymorphisms in the DNA repair genes may be associated with differences in the capacity to repair DNA damage, and so this can influence an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of hMSH2 -118T>C, IVS1+9G>C, IVS10+12A>G, and IVS12-6T>C genotypes and their haplotypes with the risk of lung cancer in a Korean population. The hMSH2 genotypes were determined in 432 lung cancer patients and in 432 healthy controls who were frequency matched for age and gender. The hMSH2 haplotypes were estimated based on a Bayesian algorithm using the Phase program. The presence of at least one IVS10+12G allele was associated with a significantly decreased risk of adenocarcinoma, as compared with the IVS10+12AA genotype [adjusted odds ratio (OR), 0.59; 95% confidence interval (95% CI), 0.40-0.88; P = 0.01], and the presence of at least one IVS12-6C allele was associated with a significantly increased risk of adenocarcinoma, as compared with the IVS12-6TT genotype (adjusted OR, 1.52; 95% CI, 1.02-2.27; P = 0.04). Consistent with the results of the genotyping analysis, the TGGT haplotype with no risk allele was associated with a significantly decreased risk of adenocarcinoma, as compared with the TCAC haplotype with two risk allele [i.e., IVS10+12A and IVS12-6C allele; adjusted OR, 0.49; 95% CI, 0.30-0.78; P = 0.003 and P(c) (Bonferroni corrected P value) = 0.012]. The effect of the hMSH2 haplotypes on the risk of adenocarcinoma was statistically significant in the never smokers and younger individuals (adjusted OR, 0.45; 95% CI, 0.27-0.75; P = 0.002 and P(c) = 0.004; and adjusted OR, 0.44; 95% CI, 0.23-0.85; P = 0.014 and P(c) = 0.028, respectively) but not in the ever-smokers and older individuals. These results suggest that the hMSH2 polymorphisms and their haplotypes may be an important genetic determinant of adenocarcinoma of the lung, particularly in never smokers.
DNA修复基因中的多态性可能与DNA损伤修复能力的差异有关，因此这可能会影响个体患肺癌的易感性。为了验证这一假设，我们在韩国人群中研究了hMSH2 -118T>C、IVS1+9G>C、IVS10+12A>G和IVS12-6T>C基因型及其单倍型与肺癌风险的关联。在432例肺癌患者和432例年龄和性别频率匹配的健康对照中确定了hMSH2基因型。使用Phase程序基于贝叶斯算法估计hMSH2单倍型。与IVS10+12AA基因型相比，至少存在一个IVS10+12G等位基因与腺癌风险显著降低相关[调整后的优势比（OR），0.59；95%置信区间（95%CI），0.40 - 0.88；P = 0.01]，与IVS12-6TT基因型相比，至少存在一个IVS12-6C等位基因与腺癌风险显著增加相关（调整后的OR，1.52；95%CI，1.02 - 2.27；P = 0.04）。与基因分型分析结果一致，与具有两个风险等位基因的TCAC单倍型[即IVS10+12A和IVS12-6C等位基因]相比，没有风险等位基因的TGGT单倍型与腺癌风险显著降低相关[调整后的OR，0.49；95%CI，0.30 - 0.78；P = 0.003，校正后的P值（P(c)）= 0.012]。hMSH2单倍型对腺癌风险的影响在从不吸烟者和年轻个体中具有统计学意义（调整后的OR，0.45；95%CI，0.27 - 0.75；P = 0.002，P(c) = 0.004；以及调整后的OR，0.44；95%CI，0.23 - 0.85；P = 0.014，P(c) = 0.028），但在曾经吸烟者和老年个体中没有统计学意义。这些结果表明，hMSH2多态性及其单倍型可能是肺腺癌的重要遗传决定因素，尤其是在从不吸烟者中。
