Jones Carissa C, Bush William S, Crawford Dana C, Wenzlaff Angela S, Schwartz Ann G, Wiencke John K, Wrensch Margaret R, Blot William J, Chanock Stephen J, Grogan Eric L, Aldrich Melinda C
Department of Thoracic Surgery, Vanderbilt University Medical School, Nashville, Tennessee.
Vanderbilt Genetics Institute, Vanderbilt University Medical School, Nashville, Tennessee.
Cancer Epidemiol Biomarkers Prev. 2017 Aug;26(8):1288-1295. doi: 10.1158/1055-9965.EPI-16-0998. Epub 2017 Jun 15.
African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases. Incident non-small cell lung cancer cases ( = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies ( = 316 and 298) were used for replication. One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54-0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71-0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33-0.66). We identified an association between rs1878022 in and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene-environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival. We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. .
非裔美国人在美国肺癌死亡率最高。尚未对影响肺癌生存的种系变异进行全基因组关联研究（GWAS），研究对象为非裔美国人。我们研究了五个先前报道的GWAS目录变异，并探索了非裔美国肺癌病例之间的其他全基因组关联。南方社区队列研究中的非小细胞肺癌新发病例（n = 286）在Illumina HumanExome BeadChip上进行基因分型。我们使用Cox比例风险模型来估计总死亡率的HR和95%置信区间（CI）。两项独立的非裔美国人研究（n = 316和298）用于重复验证。一个先前报道的位于12q23.3的变异rs1878022与死亡率显著相关（HR = 0.70；95% CI：0.54 - 0.92）。重复验证结果方向相同，尽管效应减弱（HR = 0.87和0.94）。荟萃分析的HR为0.83（95% CI，0.71 - 0.97）。常见变异分析确定6号染色体q21.33与死亡率之间存在关联（HR = 0.46；95% CI，0.33 - 0.66）。我们确定了rs1878022与肺癌生存之间的关联。然而，我们在非裔美国人中的结果与先前对欧裔美国人的研究相比，效应方向不同，这表明存在不同的遗传结构或基因 - 环境相互作用。我们还在富含基因的HLA区域内的6号染色体上鉴定出变异，该区域先前与肺癌风险和生存有关。我们发现有证据表明遗传风险因素影响非裔美国人的肺癌生存。需要在更多人群中进行重复验证，以确认不同人群肺癌生存中潜在的遗传差异。
