Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study
Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study
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DOI：
10.1007/s10147-022-02148-2
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发表时间：
2022-03-23
影响因子：
3.3
通讯作者：
Sugihara, Kenichi
中科院分区：
文献类型：
--
作者：
Fujiyoshi, Kenji;Sudo, Tomoya;Sugihara, Kenichi
背景大肠癌（CRC）的发病受内外因素的复杂相互作用影响.错配修复（MMR）基因的种系突变是导致Lynch综合征（LS）的主要内源性因素。在LS患者中，外源性因素饮酒可能与CRC发病率相关。然而，没有足够的数据来确定饮酒是否会影响与性别，MMR基因突变和解剖肿瘤部位相关的CRC首次发病时间。方法在日本LS队列中确定的316例LS患者中，我们纳入了288例患者的年龄、性别、先证者状态、饮酒状态、吸烟状态、肿瘤位置和MMR基因突变数据。多变量分析评估了饮酒与首次CRC早期发病的相关性。结果饮酒者与从不饮酒者相比，其大肠癌首次发病的危险性显著增高（HR 1.54，95%CI 1.14-2.07，P = 0.004）。CRC首次发病与饮酒的相关性在男性、致病性MLH 1和MSH 2突变携带者（与致病性MSH 6、PMS 2和EPCAM突变携带者相比）和近端结肠癌肿瘤（与远端结肠癌和直肠癌相比）中更强。结论：在日本LS队列中，饮酒与首次CRC的早期发病相关。这种关联在男性、致病性MLH 1和MSH 2突变携带者以及位于近端结肠的肿瘤中更强。我们的研究结果阐明了LS相关的致癌机制，并作为停止或停止饮酒的建议。
Background Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site. Methods Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC. Results Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14-2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer). Conclusions Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.