Importance of gastric cancer for the diagnosis and surveillance of Japanese Lynch syndrome patients.

Ikenoue T1, Arai M2, Ishioka C2, Iwama T2, Kaneko S2, Matsubara N2, Moriya Y2, Nomizu T2, Sugano K2, Tamura K2, Tomita N2, Yoshida T2, Sugihara K2, Naruse H1, Yamaguchi K1, Nojima M3, Nakamura Y4, Furukawa Y5,6; Japanese society for cancer of the colon and rectum (JSCCR).

Author information

1: Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
2: The Committee of HNPCC Registry and Genetic Testing Project, The Japanese Society for Cancer of the Colon and Rectum (JSCCR), Sanbancho KS Bldg., 2 Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan.
3: Division of Advanced Medicine Promotion, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
4: Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
5: Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. furukawa@ims.u-tokyo.ac.jp.
6: The Committee of HNPCC Registry and Genetic Testing Project, The Japanese Society for Cancer of the Colon and Rectum (JSCCR), Sanbancho KS Bldg., 2 Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan. furukawa@ims.u-tokyo.ac.jp.

Abstract

Lynch syndrome (LS) is an autosomal dominantly inherited disease predisposed to not only colorectal cancer but also other LS-related tumors. Although the clinical and genetic characteristics of LS in Western countries have been well characterized, the information of Japanese LS is limited. As a collaborative study of Japanese Society for Cancer of the Colon and Rectum (JSCCR), we registered colorectal cancer (CRC) patients who fulfilled the modified Amsterdam II criteria including gastric cancer as an LS-related tumor. Among 4030 CRC patients initially registered in this project, 85 patients (2.1%) fulfilled the modified criteria. An additional 26 patients who met the same criteria were enrolled in the analysis. We analyzed three major responsible genes, MLH1, MSH2, and MSH6 by direct sequencing, and further performed multiplex ligation-dependent probe amplification for MLH1 and MSH2. Consequently, we identified pathogenic variants in 64 of the 111 patients comprising of 34 patients in MLH1, 28 in MSH2, and 2 in MSH6. It is of note that large structural alterations were found in 17 patients. Among the 64 patients, 11 patients would not have been enrolled in the analysis if gastric cancer were not included in the modified criteria. In addition, 10 of the 64 variant carriers (15.6%) had medical history of gastric cancer. Furthermore, the standardized incidence ratio of gastric cancer in the LS patients to the Japanese population is estimated to be as high as 20.2. These data underscore the importance of gastric cancer in the diagnosis and healthcare of Japanese LS patients.