Department of 1Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):240-4. doi: 10.1158/1055-9965.EPI-09-0710.
Multiple recent genome-wide studies of single nucleotide polymorphisms (SNP) reported associations between candidate chromosome loci and lung cancer susceptibility. We evaluated five of the top candidate SNPs (rs402710, rs2736100, rs4324798, rs16969968, and rs8034191) for their effects on lung cancer risk and overall survival.
Over 1,700 cases and 2,200 controls were included in this study. Seven independent, complementary case-control data sets were tested for risk assessment encompassing cigarette smokers and never smokers, using unrelated controls and unaffected full-sibling controls. Five patient groups were tested for survival prediction stratified by smoking status, histology subtype, and treatment.
After considering a history of chronic obstructive pulmonary disease as a risk factor altering lung cancer risk and comparing to sibling controls, none of the five SNPs remained significant. However, the variant rs4324798 was significant in predicting overall survival (hazard ratio, 0.46; 95% confidence interval, 0.30-0.73; P = 0.001) in small cell lung cancer.
None of the five candidate SNPs in lung cancer risk can be confirmed in our study. The previously reported association could be explained by disparity in tobacco smoke exposure and chronic obstructive pulmonary disease history between cases and controls. Instead, we found rs4324798 to be an independent predictor in small cell lung cancer survival, warranting further elucidation of the underlying mechanisms.
多项近期的全基因组单核苷酸多态性（SNP）研究报告了候选染色体位置与肺癌易感性之间的关联。我们评估了五个顶级候选 SNP（rs402710、rs2736100、rs4324798、rs16969968 和 rs8034191）对肺癌风险和总生存期的影响。
这项研究纳入了超过 1700 例病例和 2200 例对照。使用无关对照和未受影响的全同胞对照，通过 7 个独立的、互补的病例对照数据集进行风险评估，包括吸烟者和非吸烟者。根据吸烟状况、组织学亚型和治疗对 5 个患者组进行分层以进行生存预测。
在考虑慢性阻塞性肺疾病作为改变肺癌风险的危险因素，并与同胞对照进行比较后，这 5 个 SNP 中没有一个具有统计学意义。然而，变体 rs4324798 在预测小细胞肺癌的总体生存方面具有显著意义（风险比，0.46；95%置信区间，0.30-0.73；P=0.001）。
在我们的研究中，不能确认肺癌风险的这 5 个候选 SNP。先前报告的关联可能是由于病例和对照之间的烟草暴露和慢性阻塞性肺疾病史的差异所致。相反，我们发现 rs4324798 是小细胞肺癌生存的独立预测因子，值得进一步阐明其潜在机制。
