Choi Yi Young, Kang Hyo-Kyung, Choi Jin Eun, Jang Jin Sung, Kim Eun Jin, Cha Sung Ick, Lee Won Kee, Kam Sin, Kim Chang Ho, Han Sung Beom, Jung Tae Hoon, Park Jae Yong
Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Cancer Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
J Hum Genet. 2008;53(1):87-95. doi: 10.1007/s10038-007-0222-6. Epub 2007 Nov 28.
The purpose of this study is to comprehensively evaluate potential functional polymorphisms in the P21 gene in relation to the risk of lung cancer. We first determined the frequencies of P21 polymorphisms in 27 healthy Koreans, and then examined three polymorphisms (-2266G > A, S31R, and IVS2 + 16G > C), based on their frequencies and haplotype-tagging status, in a case-control study. Individuals with at least one -2266A allele were at a significantly decreased risk of lung cancer compared with those harboring the -2266 GG genotype [adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.53-0.95, P = 0.02). The haplotypes (ht2-4) carrying 31R or IVS2 + 16C alleles were associated with a significantly decreased risk of lung cancer compared with the haplotype 31S/IVS2 + 16G, which carried wild-type alleles at both loci (adjusted OR = 0.65, 95% CI = 0.50-0.83, P = 0.007)]. When the -2266A allele and ht2-4 were considered to be protective alleles, the risk of lung cancer decreased in a dose-dependent manner as the number of protective alleles increased (P = 0.0002). These results suggest that a combined analysis of these three P21 polymorphisms might better predict the risk of lung cancer than the analysis of a single polymorphism.
本研究的目的是全面评估P21基因中的潜在功能多态性与肺癌风险的关系。我们首先确定了27名健康韩国人中P21多态性的频率，然后在一项病例对照研究中，根据其频率和单倍型标签状态，检测了三种多态性（-2266G>A、S31R和IVS2+16G>C）。与携带-2266 GG基因型的个体相比，至少携带一个-2266A等位基因的个体患肺癌的风险显著降低[调整后的优势比（OR）=0.71，95%置信区间（CI）=0.53-0.95，P=0.02]。与在两个位点均携带野生型等位基因的单倍型31S/IVS2+16G相比，携带31R或IVS2+16C等位基因的单倍型（ht2-4）与患肺癌风险显著降低相关（调整后的OR=0.65，95%CI=0.50-0.83，P=0.007）。当将-2266A等位基因和ht2-4视为保护性等位基因时，随着保护性等位基因数量的增加，肺癌风险呈剂量依赖性降低（P=0.0002）。这些结果表明，对这三种P21多态性进行联合分析可能比单一多态性分析能更好地预测肺癌风险。
