Abstract 4157: Idenitificaiton of pathogenic germline variants of patients with double primary cancer of stomach and colon

Abstract

Abstract Purpose: The incidence of multiple primary cancers has increased as survival of cancer patients has improved. The most common type of multiple primary cancers is the combination of stomach and colon cancer in Korea. Patients affected by two primary cancers at early age would be mainly related to their own genetic risk, however, germline variant of patients with double primary cancer have not been well evaluated. Methods: Patient who is with pathologically confirmed cancers in both stomach and colon in Severance hospital between January, 2000 and December, 2016 were enrolled in this study. The patients were classified into two groups: early-age group was defined as both cancers were diagnosed before 55-years, and others were considered as late-age group. The overall early-age group (n=19) and randomly selected a fourth of late-age group (n=36) were enrolled in this study. The DNA was extracted from an archived formalin fixed paraffin embedded normal mucosa that was retrospectively reviewed. Target sequencing analysis focused on 65 genes that are known to be related to hereditary cancer was conducted. The characteristics of both cancers and family history were also evaluated. Results: Overall 11 pathogenic/likely pathogenic germline variants (PGVs) were detected in nine patients (16.4%, 9/55, MLH1 [n=7], BLM [n=1], BRCA1 [n=1], MSH6 [n=1], and MSH2 [n=1]). The incidence of PGVs was 36.8% (7/19) and 5.6% (2/36) in early and late-age group, respectively (p<0.001). The early-age (Odds ratio[OR]: 9.92, 95% confidence interval [CI]: 1.81-54.49, p=0.008), Amsterdam_II criteria (OR: 24.29, 95% CI: 2.45-241.36, p=0.006), multiple lesions either gastric and colon cancer (OR: 13.13, 95% CI: 2.48-69.55, p=0.002) and mucinous/poorly differentiated histology of colon cancer (OR: 10.75, 95% CI: 1.48-78.06, p=0.019) were significant risk factors of PGVs in patients with double primary cancer at stomach and colon. Conclusions: The Lynch syndrome related PGVs were identified in patients with double primary cancer at stomach and colon. Patients with double primary cancers at stomach and colon related to early age, multiple lesions, family history especially Amsterdam_II criteria, and poorly differentiated histology of colon cancer would be good candidate for genetic evaluation. Citation Format: Yoon Young Choi, Ji Soo Park, Seung-Tae Lee, Su-Jin Shin, Jae Eun Lee, Jeong-Hyeon Jo, Eun Ji Nam, Taeil Son, Hyoung-Il Kim, Woo Jin Hyung, Sung Hoon Noh, Jae-Ho Cheong. Idenitificaiton of pathogenic germline variants of patients with double primary cancer of stomach and colon [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4157.