Introduction: The association between smoking cessation and intrahepatic and extrahepatic cholangiocarcinoma (iCCA and eCCA) risk is unclear. Furthermore, the association in individuals with preexisting risk factors is unknown. We aimed to investigate the association between smoking status (especially smoking cessation) and CCA risk according to individuals’ glycemic status. Methods: In this nationwide cohort study, 9,520,629 adults without cancer who underwent national health screening by the Korean National Health Insurance Service in 2009 were followed up through 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for CCA were estimated after adjusting for potential confounders. Results: During the 78.3 person-years of follow-up, 16,236 individuals were newly diagnosed with CCA. Quitters had a significantly lower risk of iCCA and eCCA compared to current smokers in all glycemic status groups (all P<0.01). The HRs (95% CIs) for iCCA in current smokers and quitters were 1.33 (1.24–1.43) vs. 0.98 (0.90–1.06) in individuals with normoglycemia, 1.49 (1.37–1.63) vs. 1.17 (1.06–1.28) in individuals with prediabetes, and 2.15 (1.96–2.37) vs. 1.58 (1.42–1.75) in individuals with diabetes, compared to never-smokers with normoglycemia. Current smokers with diabetes or prediabetes had a synergistically increased risk of iCCA (all P<0.01). However, quitters with diabetes and prediabetes had an iCCA risk comparable to that of never-smokers. Analysis of eCCA yielded similar results. Smoking was not independently associated with the risk of the ampulla of Vater cancer. However, smoking combined with diabetes or prediabetes was associated with an increased risk of the ampulla of Vater cancer (all P<0.05). Discussion/Conclusion: Smoking cessation was associated with a reduced risk of CCA, despite the synergistically increased risk in current smokers with diabetes and prediabetes. Our findings suggest a crucial opportunity to reduce the risk of CCA. More individualized and intensive cancer prevention education is needed against CCA.


中文翻译：

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戒烟与胆管癌和壶腹癌风险之间的关联：一项全国队列研究

简介：戒烟与肝内和肝外胆管癌（iCCA 和 eCCA）风险之间的关联尚不清楚。此外，与先前存在风险因素的个体之间的关联尚不清楚。我们旨在根据个体的血糖状况调查吸烟状况（尤其是戒烟）与 CCA 风险之间的关联。方法：在这项全国队列研究中，9,520,629 名未患癌症的成年人在 2009 年接受了韩国国民健康保险服务的全国健康筛查，并在 2018 年进行了随访。估计了 CCA 的风险比 (HR) 和 95% 置信区间 (CI)在针对潜在的混杂因素进行调整后。结果：在 78.3 人年的随访期间，有 16,236 人被新诊断为 CCA。在所有血糖状态组中，与当前吸烟者相比，戒烟者 iCCA 和 eCCA 的风险显着降低（所有 P < 0.01）。当前吸烟者和戒烟者中 iCCA 的 HR（95% CI）在血糖正常的个体中为 1.33 (1.24–1.43) 对 0.98 (0.90–1.06)，在个体中为 1.49 (1.37–1.63) 对 1.17 (1.06–1.28)与前驱糖尿病患者相比，糖尿病患者为 2.15 (1.96–2.37) vs. 1.58 (1.42–1.75)，与血糖正常的从不吸烟者相比。当前患有糖尿病或糖尿病前期的吸烟者患 iCCA 的风险协同增加（所有 P < 0.01）。然而，患有糖尿病和前驱糖尿病的戒烟者的 iCCA 风险与从不吸烟者相当。eCCA 的分析产生了类似的结果。吸烟与 Vater 壶腹癌的风险无关。然而，吸烟合并糖尿病或糖尿病前期与 Vater 壶腹癌风险增加相关（所有 P < 0.05）。讨论/结论：戒烟与 CCA 风险降低相关，尽管当前吸烟者患有糖尿病和前驱糖尿病的风险协同增加。我们的研究结果表明这是一个降低 CCA 风险的重要机会。针对CCA，需要更多个性化和强化的癌症预防教育。