A Prospective Study of Smoking and Risk of Synchronous Colorectal Cancers.
A Prospective Study of Smoking and Risk of Synchronous Colorectal Cancers.
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DOI：
10.1038/ajg.2016.589
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Ogino S
中科院分区：
文献类型：
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作者：
Drew DA;Nishihara R;Lochhead P;Kuchiba A;Qian ZR;Mima K;Nosho K;Wu K;Wang M;Giovannucci E;Fuchs CS;Chan AT;Ogino S
吸烟与体细胞遗传和表观遗传畸变有关，包括CpG岛甲基化表型（CIMP）高，微卫星不稳定性（MSI）高和BRAF突变。这些分子特征与同步原发性结直肠癌（CRC）相关。因此，我们检验了吸烟可能与同步CRC风险相关的假设。在卫生专业人员随访研究和护士健康研究中，我们根据肿瘤的同步性，使用重复方法考克斯比例风险回归分析来检查吸烟与CRC发病率的关系。我们在134，305例患者的随访中确认了1，981例孤立性CRC和45例同步性CRC病例。吸烟与结直肠癌的相关风险在肿瘤同步性状态之间存在显著差异（P异质性<0.001）。当比较当前吸烟者与从不吸烟者时，同步CRC的多变量风险比（HR）为5.27（95%置信区间[CI]，2.08-13.40），孤立CRC为0.97（95% CI，0.83-1.14）。同样，当检查累积吸烟包年数时，观察到差异相关性（P异质性=0.006）。与目前吸烟相比，戒烟≥10年可降低同步性CRC的风险（多变量HR=0.42; 95%CI，0.19-0.95），但不能降低孤立性CRC的风险（多变量HR=1.10; 95%CI，0.94-1.29）（P异质性=0.001）。比较当前和既往吸烟者与从不吸烟者，同步CRC的多变量HR显著高于CIMP高、MSI高或BRAF突变阳性的单发CRC（P异质性=0.002）。吸烟与同步CRC的风险升高有关。我们的数据支持这样一个模型，即吸烟有助于病因学领域的影响，有利于这些体细胞分子的改变和多原发性肿瘤的发展。
Cigarette smoking has been linked to somatic genetic and epigenetic aberrations, including CpG island methylator phenotype (CIMP)-high, microsatellite instability (MSI)-high, and BRAF mutation. These molecular features have been associated with synchronous primary colorectal cancers (CRCs). Thus, we examined the hypothesis that smoking might be associated with the risk of synchronous CRCs. Within the Health Professionals Follow-up Study and Nurses’ Health Study, we examined the relationship of smoking and incidence of CRC according to tumor synchronicity, using duplication-method Cox proportional hazards regression analysis. We confirmed 1,981 solitary CRC and 45 synchronous CRC cases during follow up of 134,305 individuals. CRC risk associated with smoking differed significantly by tumor synchronicity status (Pheterogeneity<0.001). When comparing current smokers with never smokers, multivariable hazard ratios (HR) were 5.27 (95% confidence interval [CI], 2.08–13.40) for synchronous CRCs and 0.97 (95% CI, 0.83–1.14) for solitary CRC. Similarly, differential associations were observed when examining cumulative pack-years smoked (Pheterogeneity=0.006). Smoking cessation for ≥10 years relative to current smoking might reduce the risk of synchronous CRCs (multivariable HR=0.42; 95% CI, 0.19–0.95), but not solitary CRC (multivariable HR=1.10; 95% CI, 0.94–1.29)(Pheterogeneity=0.001). Comparing current and former smokers with never smokers, multivariable HRs for synchronous CRCs were significantly higher than those of solitary CRC positive for either CIMP-high, MSI-high, or BRAF mutation (Pheterogeneity=0.002). Smoking is associated with an elevated risk of synchronous CRCs. Our data support a model where smoking contributes to an etiologic field effect that favors these somatic molecular alterations and the development of multiple primary tumors.