Vasen H F, Wijnen J T, Menko F H, Kleibeuker J H, Taal B G, Griffioen G, Nagengast F M, Meijers-Heijboer E H, Bertario L, Varesco L, Bisgaard M L, Mohr J, Fodde R, Khan P M
The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands.
Gastroenterology. 1996 Apr;110(4):1020-7. doi: 10.1053/gast.1996.v110.pm8612988.
BACKGROUND & AIMS: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within affected families. The purpose of this study was to assess the age-specific cancer risk in a large series of gene carriers.
Thirty-four families were studied by mutation analysis. In 19 of these families, pathogenic mutations were found at hMSH2 or hMLH1. Of 382 relatives, 124 had a mutation in hMLH1 and 86 in hMSH2.
The lifetime risk of colorectal cancer was the same in both groups of gene carriers (80%). The risk of endometrial cancer was greater in hMSH2 gene carriers compared with hMLH1 gene carriers (61% vs. 42%), but the difference was not statistically significant. A very high relative risk of cancer of the small bowel (relative risk of >100) was observed in carriers of either gene. Only the carriers of hMSH2 mutations had a significantly increased relative risk of cancer of the urinary tract (kidney and ureter) (relative risk of 75.3), stomach (relative risk of 19.3), and ovaries (relative risk of 8.0).
This study provides estimates of cancer risk that may contribute to the appropriate management of gene carriers within families with hereditary nonpolyposis colorectal cancer.
遗传性非息肉病性结直肠癌的特征为早发性结直肠癌以及多种其他癌症的发生。最近分离出的四个与遗传性非息肉病性结直肠癌相关的错配修复基因，使得能够在受影响的家族中识别携带者。本研究的目的是评估大量基因携带者中特定年龄的癌症风险。
通过突变分析对34个家族进行了研究。在其中19个家族中，在hMSH2或hMLH1发现了致病突变。在382名亲属中，124人在hMLH1中有突变，86人在hMSH2中有突变。
两组基因携带者患结直肠癌的终生风险相同（80%）。与hMLH1基因携带者相比，hMSH2基因携带者患子宫内膜癌的风险更高（61%对42%），但差异无统计学意义。在任一基因的携带者中均观察到小肠癌的相对风险非常高（相对风险>100）。只有hMSH2突变携带者患泌尿系统（肾和输尿管）癌（相对风险为75.3）、胃癌（相对风险为19.3）和卵巢癌（相对风险为8.0）的相对风险显著增加。
本研究提供了癌症风险估计，这可能有助于对遗传性非息肉病性结直肠癌家族中的基因携带者进行适当管理。
