A second genetic variant on chromosome 15q24-25.1 associates with lung cancer.
A second genetic variant on chromosome 15q24-25.1 associates with lung cancer.
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DOI：
10.1158/0008-5472.can-09-3583
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发表时间：
2010-04-15
期刊：
影响因子：
11.2
通讯作者：
You M
中科院分区：
文献类型：
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作者：
Liu P;Yang P;Wu X;Vikis HG;Lu Y;Wang Y;Schwartz AG;Pinney SM;de Andrade M;Gazdar A;Gaba C;Mandal D;Lee J;Kupert E;Seminara D;Minna J;Bailey-Wilson JE;Spitz M;Amos CI;Anderson MW;You M
染色体区域15 q24 -25.1上的一个常见变异，标记为rs 1051730，被发现与肺癌风险相关。在这里，我们试图在几个大的散发性肺癌人群中确认15 q24 -25.1上的第二种变异，并确定第二种变异的遗传效应导致肺癌额外风险的百分比。在来自四个人群的2，818例肺癌病例和2，766例对照中对SNPs rs 1051730和rs 481134进行基因分型。对15 q24 -25.1上这两个变异（rs 1051730和rs 481134）的联合分析确定了三种主要的单倍型（G_T，A_C和G_C），并为15 q24 -25.1与肺癌的关联提供了更有力的证据（P = 9.72 × 10−9）。这两种变异代表了与肺癌相关的三种风险水平。最常见的单倍型G_T是中性的，单倍型A_C与肺癌风险增加相关，病例组比对照组高5.0%[P = 1.68 × 10 - 7; OR为1.24; 95%可信区间（95%CI）为1.14-1.35];而单倍型G_C与肺癌风险降低相关，病例组比对照组低4.4%（P = 7.39 × 10−7; OR，0.80; 95%CI，0.73-0.87）。我们进一步发现，15 q24 -25.1上的这两种遗传变异独立影响肺癌风险（rs 1051730：P = 4.42 × 10−11; OR，1.60; 95%CI，1.46-1.74; rs 481134：P = 7.01 × 10−4; OR，0.81; 95%CI，0.72-0.92）。15 q24 -25.1上的第二个变异，标记为rs 481134，解释了肺癌人群归因风险的额外13.2%。
A common variant on chromosomal region 15q24–25.1, marked by rs1051730, was found to be associated with lung cancer risk. Here, we attempted to confirm the second variant on 15q24–25.1 in several large sporadic lung cancer populations and determined what percentage of additional risk for lung cancer is due to the genetic effect of the second variant. SNPs rs1051730 and rs481134 were genotyped in 2,818 lung cancer cases and 2,766 controls from four populations. Joint analysis of these two variants (rs1051730 and rs481134) on 15q24–25.1 identified three major haplotypes (G_T, A_C, and G_C) and provided stronger evidence for association of 15q24–25.1 with lung cancer (P = 9.72 × 10−9). These two variants represent three levels of risk associated with lung cancer. The most common haplotype G_T is neutral; the haplotype A_C is associated with increased risk for lung cancer with 5.0% higher frequency in cases than in controls [P = 1.68 × 10−7; odds ratio (OR), 1.24; 95% confidence interval (95% CI), 1.14–1.35]; whereas the haplotype G_C is associated with reduced risk for lung cancer with 4.4% lower frequency in cases than in controls (P = 7.39 × 10−7; OR, 0.80; 95% CI, 0.73–0.87). We further showed that these two genetic variants on 15q24–25.1 independently influence lung cancer risk (rs1051730: P = 4.42 × 10−11; OR, 1.60; 95% CI, 1.46–1.74; rs481134: P = 7.01 × 10−4; OR, 0.81; 95% CI, 0.72–0.92). The second variant on 15q24–25.1, marked by rs481134, explains an additional 13.2% of population attributable risk for lung cancer.