Van Dyke Alison L, Cote Michele L, Wenzlaff Angela S, Abrams Judith, Land Susan, Iyer Priyanka, Schwartz Ann G
Cancer Biology Program, School of Medicine, Wayne State University, 4100 John R, Detroit, MI 48201, USA.
J Cancer Epidemiol. 2009;2009:242151. doi: 10.1155/2009/242151. Epub 2010 Feb 18.
In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.
在一项基于人群的病例对照研究中,我们探讨了该区域七个基因中的42个多态性与高加索女性(364例病例;380例对照)和非裔美国女性(95例病例;103例对照)非小细胞肺癌(NSCLC)风险之间的关联。两个端粒酶逆转录酶(TERT)区域单核苷酸多态性(SNP),即rs2075786和rs2853677,会增加患NSCLC的风险,尤其是在非裔美国女性中,而TERT-rs2735940与非裔美国人患肺癌风险降低有关。生长激素受体(GHR)的20个多态性中有5个以及硒蛋白P1(SEPP1)-rs6413428与高加索人患NSCLC的风险略有增加有关。随机森林分析强化了GHR在高加索人中的重要性,并确定了非裔美国人中的α-甲基酰基辅酶A消旋酶(AMACR)、TERT和GHR,使用基于基因的风险评分时它们也具有显著性。我们探索了吸烟与SNP的相互作用,并确定了与NSCLC风险相关的TERT和GHR单倍型。TERT、GHR、AMACR和SEPP1基因在肺癌发生中的作用值得进一步探索。