The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung
The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung
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DOI：
10.1093/carcin/bgp131
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发表时间：
2009-08-01
期刊：
影响因子：
4.7
通讯作者：
Haugen, Aage
中科院分区：
文献类型：
--
作者：
Zienolddiny, Shanbeh;Skaug, Vidar;Haugen, Aage
全基因组关联研究提供的证据表明，5p15.33 [端粒酶逆转录酶（TERT）-唇腭裂跨膜1样（CLPTM 1 L）]，6p21.33和15q25.1（CHRNA 5-CHRNA 3）的常见变异影响肺癌风险和具有强烈环境风险因素的癌症类型。为了独立验证这些关联，我们比较了365例非小细胞肺癌病例和440例对照的5p15.33（rs 402710，rs 401681），6p21.33（rs 4324798）和15q25.1（rs 1051730，rs 16969968和rs 8034191）基因型。与已发表的数据一致，5 p15（rs 402710），6p 21和15 q25的变异基因型与肺癌风险呈剂量依赖性相关。为了研究变异是否影响环境危险因素对肺癌发生的影响，我们研究了204例肺癌病例中肿瘤旁肺组织中大体积芳香族/疏水性DNA加合物的基因型和水平之间的关系。rs 402710（TERT-CLPTM 1 L基因座）的风险等位基因与显着较高水平的大体积芳香族/疏水性DNA加合物（P = 0.02）。这些数据表明TERT-CLPTM 1 L变异体和通过（32）P-后标记测量的大体积DNA加合物水平之间存在潜在关联，因此是肺癌发生易感性的基础。
Genome-wide association studies have provided evidence that common variation at 5p15.33 [telomerase reverse transcriptase (TERT)-cleft lip and palate transmembrane 1-like (CLPTM1L)], 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) influences lung cancer risk and cancer types with strong environmental risk factors. To independently validate these associations, we compared 5p15.33 (rs402710, rs401681), 6p21.33 (rs4324798) and 15q25.1 (rs1051730, rs16969968 and rs8034191) genotypes in 365 non-small cell lung cancer cases and 440 controls. Consistent with published data, variant genotypes of 5p15 (rs402710), 6p21 and 15q25 showed dose-dependent associations with lung cancer risk. To examine if variants influence the impact of environmental risk factors on lung carcinogenesis, we studied the relationship between genotype and levels of bulky aromatic/hydrophobic DNA adducts in lung tissue adjacent to tumor from 204 lung cancer cases. The risk allele of rs402710 (TERT-CLPTM1L locus) was associated with significantly higher levels of bulky aromatic/hydrophobic DNA adducts (P = 0.02). These data demonstrate a potential association between the TERT-CLPTM1L variant and levels of bulky DNA adducts measured by (32)P-postlabeling and hence a basis for susceptibility to the development of lung cancer.