The cumulative effect of single-nucleotide polymorphisms (SNPs) on thyroid cancer has been adequately defined in individuals of European ancestry; however, similar evidence in the Korean population is limited. This study aimed to investigate the influence of modifiable factors and the polygenic risk score (PRS) and their interactive and combined effects on thyroid cancer. Using data from the cancer screenee cohort, this study included 759 thyroid cancer cases and 759 age- and sex-matched controls. We examined the effects of tobacco smoking, alcohol consumption, and regular exercise habits, BMI, and the PRS of six SNPs on thyroid cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations were obtained using a conditional logistic regression model. The results indicated that family history, obesity, and the unweighted and weighted PRS were independently associated with susceptibility to thyroid cancer, with ORs (95% CIs) of 2.96 (1.63-5.36), 1.72 (1.20-2.48), 1.46 (1.10-1.93), and 1.56 (1.19-2.03), respectively, whereas the effect of smoking, drinking, and regular exercise was not significant. The contribution of the PRS remained after stratifying participants with healthy behaviors, such as nonsmokers/nondrinkers, and regular exercise. Although the PRS did not significantly contribute to the risk for thyroid cancer when participants were stratified according to BMI, BMI and the PRS had a cumulative effect on thyroid cancer risk. The combined effect of genetic polymorphisms on predisposition to thyroid cancer may differ based on tobacco smoking, alcohol consumption, regular exercise behaviors and cumulative BMI. Larger population-based studies are needed to validate these findings.

中文翻译：

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甲状腺癌中可改变因素和多基因风险评分的评估。

单核苷酸多态性 (SNP) 对甲状腺癌的累积效应已在欧洲血统的个体中得到充分定义；然而，在韩国人群中的类似证据是有限的。本研究旨在探讨可改变因素和多基因风险评分（PRS）的影响及其对甲状腺癌的交互作用和综合作用。使用来自癌症筛查人群的数据，本研究包括 759 例甲状腺癌病例和 759 例年龄和性别匹配的对照。我们检查了吸烟、饮酒和定期运动习惯、BMI 和六个 SNP 的 PRS 对甲状腺癌的影响。使用条件逻辑回归模型获得关联的优势比 (OR) 和 95% 置信区间 (CI)。结果表明，家族史、肥胖、未加权和加权 PRS 与甲状腺癌易感性独立相关，ORs (95% CIs) 分别为 2.96 (1.63-5.36)、1.72 (1.20-2.48)、1.46 (1.10-1.93) 和 1.56 (1.19-2.03) )，而吸烟、饮酒和定期运动的影响并不显着。在对具有健康行为的参与者（例如不吸烟者/不饮酒者）和定期锻炼进行分层后，PRS 的贡献仍然存在。尽管根据 BMI 对参与者进行分层时，PRS 对甲状腺癌风险没有显着影响，但 BMI 和 PRS 对甲状腺癌风险具有累积效应。遗传多态性对甲状腺癌易感性的综合影响可能因吸烟、饮酒、定期运动行为和累积 BMI 而异。