Washington University, St. Louis, MO 63110, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):517-24. doi: 10.1158/1055-9965.EPI-09-0791.
Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for.
One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio.
SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 x 10(-4); odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 x 10(-6)) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers.
The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer.
遗传因素在肺癌易感性中起着重要作用。在这项研究中，我们复制了 5p15.33 和 6p21.33 与家族性肺癌的关联。考虑到先前在 6q23-25/RGS17 和 15q24-25.1 上确定的遗传易感性变异，我们进一步确定了这四个遗传区域的累积关联以及它们所占家族性肺癌的人群归因风险百分比。
使用来自肺癌遗传流行病学联盟的 194 例病例患者和 219 例无癌症对照进行关联分析。每个家族性病例均选自一个具有三个或更多受影响成员的高危肺癌家族。评估染色体区域 5p15.33、6p21.33、6q23-25/RGS17 和 15q24-25.1 上的单核苷酸多态性（SNP）与家族性肺癌的关联。使用线性逻辑回归模型评估四个染色体区域与家族性肺癌的累积关联。使用风险比计算每个 SNP 的人群归因风险百分比。
SNP rs31489 在 5p15.33 上显示出与家族性肺癌最强的关联证据（P=2x10(-4)；比值比，0.57；95%置信区间，0.42-0.77），而 SNP rs3117582 在 6p21.33 上显示出较弱的关联（P=0.09；比值比，1.47；95%置信区间，0.94-2.31）。来自四个区域的 SNP 组合分析提供了与家族性肺癌更强的累积关联（P=6.70x10(-6)），比任何单个 SNP 都要强。与没有任何危险因素的受试者相比，那些在每个区域至少有一个风险等位基因的受试者患肺癌的风险增加了 3 至 11 倍。这四个遗传区域共占吸烟者家族性肺癌的 34.6%。
四个染色体区域中的 SNP 与家族性肺癌具有累积和显著的关联，占家族性肺癌人群归因风险的约三分之一。
