Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome
Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome
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DOI：
10.1093/jnci/djs351
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发表时间：
2012-09-01
影响因子：
10.3
通讯作者：
Jenkins, Mark A.
中科院分区：
文献类型：
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作者：
Win, Aung Ko;Lindor, Noralane M.;Jenkins, Mark A.
林奇综合征是一种由DNA错配修复(MMR)基因种系突变引起的高度渗透性癌症易感综合征。我们从结肠癌家族登记处获得了764名MMR基因突变携带者(316名MLH1、357名MSH2、49名MSH6和42名PMS2)的数据，这些人以前曾被诊断为结直肠癌，因此我们评估了在突变携带者中诊断为结直肠癌后发生结直肠癌以外的原发癌症的风险。Kaplan Meier方法被用来估计他们在结直肠癌10年和20年后患癌症的累积风险。在结直肠癌之后，携带MMR基因突变的人有以下10年的其他器官癌症的风险：肾、肾盂、输尿管和膀胱癌(2%，95%可信区间=1%到3%)；小肠、胃和肝胆管(1%，95%CI=0.2%到2%)；前列腺癌(3%，95%CI=1%到5%)；子宫内膜(12%，95%CI=8%~17%)、乳房(2%，95%CI=1%~4%)、卵巢(1%，95%CI=0%~2%)。与一般人群相比，高危人群依次为肾癌(SIR=12.5 4，95%CI=7.97~17.94)、膀胱癌(SIR=7.2 2，95%CI=4.0 8~10.99)、小肠(SIR=72.6 8，95%CI=39.95~111.29)、胃癌(SIR=5.6 5，95%CI=2.32~9.69)、肝胆管(SIR=5.94，95%CI=1.81~10.94)；前列腺癌(SIR=2.05，95%CI=1.23~3.01)、子宫内膜癌(SIR=40.23，95%CI=27.91~56.06)、乳腺癌(SIR=1.76，95%CI=1.07~2.59)和卵巢癌(SIR=4.19，95%CI=1.28~7.97)。与公认的Lynch综合征癌症谱相比，已经患有结直肠癌的MMR基因突变携带者患更广泛癌症的风险更高。
Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers.We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The KaplanMeier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar periodspecific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population.Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97).Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.