Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, VIC, Australia.
Int J Cancer. 2011 Nov 1;129(9):2256-62. doi: 10.1002/ijc.25870. Epub 2011 Apr 8.
Cancer risks for a person who has inherited a MUTYH mutation from only one parent (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179 first- and second-degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia. Using Cox regression weighted to adjust for sampling on family history, we estimated that the country-, age- and sex-specific standardized incidence ratios (SIRs) for monoallelic mutation carriers, compared to the general population, were: 2.04 (95% confidence interval, CI 1.56-2.70; p < 0.001) for CRC, 3.24 (95%CI 2.18-4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07-12.25; p = 0.07) for liver cancer and 2.33 (95%CI 1.18-5.08; p = 0.02) for endometrial cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs and US population incidences, were: for CRC, 6% (95%CI 5-8%) for men and 4% (95%CI 3-6%) for women; for gastric cancer, 2% (95%CI 1-3%) for men and 0.7% (95%CI 0.5-1%) for women; for liver cancer, 1% (95%CI 0.3-3%) for men and 0.3% (95%CI 0.1-1%) for women and for endometrial cancer, 4% (95%CI 2-8%). There was no evidence of increased risks for cancers of the brain, pancreas, kidney, lung, breast or prostate. Monoallelic MUTYH mutation carriers with a family history of CRC, such as those identified from screening multiple-case CRC families, are at increased risk of colorectal, gastric, endometrial and possibly liver cancers.
携带有从父母一方遗传的 MUTYH 突变（单等位基因突变携带者）的个体的癌症风险尚不确定。利用结肠癌家族登记处和纽芬兰家族性结肠癌登记处，我们确定了 144 例结直肠癌（CRC）病例的一级和二级亲属 2179 人，他们是通过在美国、加拿大和澳大利亚的人群完整癌症登记处取样确定的单等位基因突变或双等位基因突变携带者。我们使用 Cox 回归进行加权调整，以调整家族史的抽样，结果表明，与一般人群相比，单等位基因突变携带者的国家、年龄和性别特异性标准化发病比（SIR）为：CRC 为 2.04（95%置信区间，1.56-2.70；p<0.001）、胃癌为 3.24（95%置信区间，2.18-4.98；p<0.001）、肝癌为 3.09（95%置信区间，1.07-12.25；p=0.07）和子宫内膜癌为 2.33（95%置信区间，1.18-5.08；p=0.02）。使用 SIR 和美国人群发病率估算的 70 岁以下年龄的特定累积风险为：CRC 为男性 6%（95%置信区间，5-8%）和女性 4%（95%置信区间，3-6%）；胃癌为男性 2%（95%置信区间，1-3%）和女性 0.7%（95%置信区间，0.5-1%）；肝癌为男性 1%（95%置信区间，0.3-3%）和女性 0.3%（95%置信区间，0.1-1%）；子宫内膜癌为 4%（95%置信区间，2-8%）。没有证据表明脑癌、胰腺癌、肾癌、肺癌、乳腺癌或前列腺癌的风险增加。携带有结直肠癌家族史的单等位基因突变 MUTYH 突变携带者（如从筛查多例结直肠癌家族中发现的）患有结直肠癌、胃癌、子宫内膜癌和可能的肝癌的风险增加。
