Prevalence of cancer susceptibility variants in patients with multiple Lynch syndrome related cancers

Abstract Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of pathogenic variants in MPC patients often unknown. We screened 71 stomach, colorectal, and endometrium, sequencing 65 cancer genes. A subset 19 stomach colorectum were further evaluated for related using both normal tumor whole exome sequencing. Among MPCs, classified to be observed 15 (21.1%) affected Lynch Syndrome (LS) genes: MLH1 (n = 10), MSH6 2), PMS2 MSH2 1). All carriers had tumors high microsatellite instability 13 them (86.7%) early-onset, consistent LS. In loss function (LoF) RECQL5 more prevalent non-LS than matched sporadic (OR 31.6, 2.73–1700.6, p 0.001). Additionally, there high-confidence LoF at FANCG CASP8 two accompanied by somatic heterozygosity tumor, respectively. The results suggest that screening should considered synchronous metachronous MPCs LS spectrum, particularly early-onset. Susceptibility may exist, but evidence their role is elusive patients.