Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
BMC Cancer. 2017 Dec 19;17(1):869. doi: 10.1186/s12885-017-3886-0.
Although genome-wide association studies (GWAS) have identified variants in approximately 40 susceptibility loci for colorectal cancer (CRC), there are few studies on the interactions between identified single-nucleotide polymorphisms (SNPs) and lifestyle risk factors. We evaluated whether smoking could modify associations between these genetic variants and CRC risk.
A total of 703 CRC patients and 1406 healthy controls were included in this case-control study from the National Cancer Center in Korea. Thirty CRC susceptibility SNPs identified in previous GWAS were genotyped. A logistic regression model was used to examine associations between the SNPs and smoking behaviors by sex. The interaction was estimated by including an additional interaction term in the model.
In men, an increased CRC risk was observed for longer durations (OR = 1.49 (95% CI = 1.11-1.98)), greater quantities (OR = 2.12 (1.61-2.79)), and longer pack-years of smoking (OR = 1.78 (1.35-2.35)). In women, longer pack-years of smoking significantly increased CRC risk (OR = 6.11 (1.10-34.00)). Moreover, there were significant interactions between smoking status and the polymorphisms rs1957636 at 14q22.3 (P = 5.5 × 10) and rs4813802 at 20p12.3 (P = 0.04) in men. Interactions between smoking status and the rs6687758 at 1q41 (P = 0.03), duration and the rs174537 at 11q12.2 (P = 0.05), and pack-years and the rs4813802 (P = 0.04) were also found in women.
Associations between susceptibility SNPs and CRC risk may be modified by smoking behaviors, supporting the existence of gene-smoking interactions.
尽管全基因组关联研究（GWAS）已经确定了大约 40 个结直肠癌（CRC）易感性位点的变异，但对于已确定的单核苷酸多态性（SNP）与生活方式危险因素之间的相互作用的研究较少。我们评估了吸烟是否可以改变这些遗传变异与 CRC 风险之间的关联。
这项病例对照研究共纳入了 703 名 CRC 患者和 1406 名健康对照，来自韩国国家癌症中心。对之前 GWAS 中确定的 30 个 CRC 易感性 SNP 进行了基因分型。通过按性别使用逻辑回归模型检查 SNP 与吸烟行为之间的关联。通过在模型中添加额外的交互项来估计交互作用。
在男性中，观察到吸烟时间更长（OR=1.49（95%CI=1.11-1.98））、吸烟量更大（OR=2.12（1.61-2.79））和更长的吸烟包年数（OR=1.78（1.35-2.35））与 CRC 风险增加相关。在女性中，较长的吸烟包年数显著增加 CRC 风险（OR=6.11（1.10-34.00））。此外，在男性中，吸烟状态与 rs1957636 多态性（位于 14q22.3，P=5.5×10）和 rs4813802 多态性（位于 20p12.3，P=0.04）之间存在显著的交互作用。在女性中，也发现了吸烟状态与 rs6687758 多态性（位于 1q41，P=0.03）、吸烟时间与 rs174537 多态性（位于 11q12.2，P=0.05）和吸烟包年数与 rs4813802 多态性（P=0.04）之间的交互作用。
SNP 与 CRC 风险之间的关联可能受到吸烟行为的修饰，支持基因-吸烟相互作用的存在。
