Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC, 3000, Australia.
Br J Cancer. 2019 Nov;121(10):869-876. doi: 10.1038/s41416-019-0580-9. Epub 2019 Sep 25.
Type 2 diabetes mellitus and high total cholesterol and triglycerides are known to be associated with increased colorectal cancer risk for the general population. These associations are unknown for people with a germline DNA mismatch repair gene mutation (Lynch syndrome), who are at high risk of colorectal cancer.
This study included 2023 (56.4% female) carriers with a mismatch repair gene mutation (737 in MLH1, 928 in MSH2, 230 in MSH6, 106 in PMS2, 22 in EPCAM) recruited by the Colon Cancer Family Registry between 1998 and 2012. Weighted Cox regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the associations between self-reported type 2 diabetes, high cholesterol, triglyceride and colorectal cancer risk.
Overall, 802 carriers were diagnosed with colorectal cancer at a median age of 42 years. A higher risk of colorectal cancer was observed in those with self-reported type-2 diabetes (HR 1.92; 95% CI, 1.03-3.58) and high cholesterol (HR 1.76; CI 1.23-2.52) compared with those without these conditions. There was no evidence of high triglyceride being associated with colorectal cancer risk.
For people with Lynch syndrome, self-reported type-2 diabetes mellitus and high cholesterol were associated with increased colorectal cancer risk.
2 型糖尿病和总胆固醇及甘油三酯高与一般人群结直肠癌风险增加有关。对于存在种系 DNA 错配修复基因突变（林奇综合征）的人群，这些关联尚不清楚，他们结直肠癌风险很高。
本研究纳入了 1998 年至 2012 年间结肠直肠癌家族登记处招募的 2023 名（56.4%为女性）错配修复基因突变携带者（MLH1 中有 737 例，MSH2 中有 928 例，MSH6 中有 230 例，PMS2 中有 106 例，EPCAM 中有 22 例）。采用加权 Cox 回归估计了报告的 2 型糖尿病、高胆固醇、甘油三酯与结直肠癌风险之间的关联的风险比（HR）和 95%置信区间（CI）。
总体而言，802 名携带者在 42 岁的中位年龄被诊断为结直肠癌。与无这些情况的携带者相比，报告有 2 型糖尿病（HR 1.92；95%CI，1.03-3.58）和高胆固醇（HR 1.76；CI，1.23-2.52）的携带者结直肠癌风险更高。没有证据表明高甘油三酯与结直肠癌风险相关。
对于林奇综合征患者，报告的 2 型糖尿病和高胆固醇与结直肠癌风险增加有关。
