Genetic susceptibility to bladder cancer in a cohort of 51 Lebanese patients

Abstract IntroductionBladder cancer (BC) is a highly prevalent malignancy worldwide and particularly in Lebanon. Several studies have reported genetic risk factors in GSTM1 and NAT2, as well as many modifiable and non-modifiable risk factors, associated with BC.MethodsThis is a retrospective study that includes 51 Lebanese patients with BC. Peripheral blood samples were collected from patients and DNA extraction was performed using the standard salting-out method. Whole exome sequencing (WES) was performed and was followed by a thorough analysis of GSTM1, NAT2 and a panel of 127 genes known to be implicated in different hereditary cancers, for the detection of pathogenic germline mutations in the studied individuals.ResultsOur cohort included 42 men (82.4%) and 9 women (17.6%), with a mean age at diagnosis equal to 67 years. Of all participants, 10.8% had a family member diagnosed with BC and 17.3% with other cancer types. Our WES analysis allowed the detection of a high-risk variant found in APC (rs1801155) and a variant in BRIP1 (rs28903098) that are frequent in our cohort and more prevalent in our Lebanese in-house database compared to other international databases. Furthermore, two actionable variants, one in PALB2 (rs864622498) and another in ERCC2 (rs121913016) were detected in 2 different individuals from our cohort, paving the way to personalized therapies in these patients. A variant in NAT2 (rs1799931), shown to be associated with BC in other populations, was detected in 4 patients from our cohort.ConclusionThis is the first study in Lebanon and one of very few international studies carried out by NGS in patients with BC. Further studies in larger cohorts are required to confirm our findings in the Lebanese population.