Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations
Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations
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DOI：
10.1111/j.1399-0004.2008.01125.x
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Evans, D. G.
中科院分区：
文献类型：
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作者：
Barrow, E.;Robinson, L.;Evans, D. G.
巴罗E，罗宾逊L，Alduaij W，Shenton A，Clancy T，Lalloo F，Hill J，Evans DG. Lynch综合征中结肠外癌的累积终生发病率：一份121个已证实突变的家族的报告。临床遗传学2009：75：141-149。(C)Blackwell Munksgaard，2009林奇综合征或遗传性非息肉病性结直肠癌是由DNA错配修复（MMR）基因突变引起的。结肠外肿瘤谱包括子宫内膜、卵巢、胃、小肠、胰腺、肝胆、脑和尿路上皮肿瘤。根据临床标准对家庭进行了转诊。进行肿瘤免疫组织化学和微卫星检测。适当的患者进行MMR基因相关外显子的测序。根据每个年龄组中未受影响的亲属检测阳性的比例，将非特异性和专性突变携带者和患有林奇综合征谱系癌症的一级亲属（FDR）视为突变携带者，也将未受影响的FDR视为突变携带者。计算了70岁风险的Kaplan-Meier分析。分析了839例确诊、专性或假定突变携带者中的184例林奇综合征谱系结肠外癌。女性结肠外肿瘤的累积风险为47.4%（95% CI 43.9-50.8）。男性的风险为26.5%（95% CI 22.6-30.4）。妇科筛查（检查、经阴道超声扫描、宫腔镜检查和子宫内膜活检）并未减少妇科恶性肿瘤。男性患胃癌的风险高于女性（p = 0.0003）。1935年以后出生的人的胃癌风险不值得监测。这些预测率估计值已针对确定偏倚进行了校正，适用于高风险诊所。
Barrow E, Robinson L, Alduaij W, Shenton A, Clancy T, Lalloo F, Hill J, Evans DG. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations.Clin Genet 2009: 75: 141-149. (C) Blackwell Munksgaard, 2009Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan-Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9-50.8). The risk to males is 26.5% (95% CI 22.6-30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.