MLH1/MSH2遗传性非息肉病性结直肠癌家系及一般人群中结直肠癌和结外癌的变异情况。

Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population.

作者信息

Lin K M, Shashidharan M, Ternent C A, Thorson A G, Blatchford G J, Christensen M A, Lanspa S J, Lemon S J, Watson P, Lynch H T

机构信息

Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska 68131-2197, USA.

出版信息

Dis Colon Rectum. 1998 Apr;41(4):428-33. doi: 10.1007/BF02235755.

DOI:10.1007/BF02235755

PMID:9559626

Abstract

PURPOSE

This clinical case review aimed to identify phenotypic variations in colorectal and extracolonic cancer expression between hereditary nonpolyposis colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the general population.

METHODS

Colorectal cancer onset and site distribution were compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and 1,189 patients from the general population. Synchronous and metachronous cancer rates, tumor stage, extracolonic cancer incidence, and survival were also compared.

RESULTS

Mean ages of colorectal cancer onset were 44, 46, and 69 years for MLH1, MSH2, and the general population, respectively (P < 0.001). More proximal and fewer distal colon cancers were noted in HNPCC than the general population (P < 0.001, P = 0.04). Site distribution showed disparity of rectal cancers (8 percent MLH1 vs. 28 percent MSH2; P = 0.01) based on genotypes. Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for MLH1, MSH2, and the general population, respectively (P = 0.016). Annual metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1, MSH2, and the general population, respectively (P = 0.041). Colorectal cancer stage presentation was lower in HNPCC than the general population (P = 0.0028). Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12 percent of MLH1 patients and 7.3 percent of the general population with colorectal cancers (P < 0.001). Combined MLH1 and MSH2 ten-year survival was 68.7 percent compared with 47.8 percent for the general population (P = 0.009 stage stratified, hazard ratio 0.57).

CONCLUSION

The presence of rectal cancer should not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in MSH2 was comparable with that in the general population. Phenotypic variations, including the preponderance of extracolonic cancers in MSH2 patients, did not result in survival differences between genotypic subgroups. These phenotypic features of HNPCC genotypes may have clinical significance in the design of specific screening, surveillance, and follow-up for affected individuals.

摘要

目的

本临床病例回顾旨在确定携带MLH1和MSH2种系突变的遗传性非息肉病性结直肠癌（HNPCC）家族与普通人群在结直肠癌及结外癌表达方面的表型差异。

方法

比较了MLH1家族的67名成员、MSH2家族的45名成员以及1189名普通人群患者的结直肠癌发病情况和部位分布。还比较了同时性和异时性癌症发生率、肿瘤分期、结外癌发病率及生存率。

结果

MLH1、MSH2和普通人群的结直肠癌平均发病年龄分别为44岁、46岁和69岁（P < 0.001）。与普通人群相比，HNPCC患者近端结肠癌更多，远端结肠癌更少（P < 0.001，P = 0.04）。根据基因型，部位分布显示直肠癌存在差异（MLH1为8%，MSH2为28%；P = 0.01）。总体而言，MLH1、MSH2和普通人群的同时性结直肠癌发生率分别为7.4%、6.7%和2.4%（P = 0.016）。MLH1、MSH2和普通人群的年度异时性结直肠癌发生率分别为2.1%、1.7%和0.33%（P = 0.041）。HNPCC患者的结直肠癌分期低于普通人群（P = 0.0028）。33%的MSH2患者发生了结外癌，而MLH1患者为12%，普通结直肠癌患者为7.3%（P < 0.001）。MLH1和MSH2联合的十年生存率为68.7%，而普通人群为47.8%（P = 0.009，分期分层，风险比0.57）。