Over the past decade an increase in the incidence and severity of multiple primary neoplasias has been observed. The main causes of multiple primary tumors (MPT) are genetic factors, environmental factors, infections with oncogenic viruses, etc. The aim of the current study was to explore the role of genes associated with familial cancers in MPT development.
The study included 12 MPT patients, of which 6 women with metahronous/synchronous breast and ovarian tumors; and 6 men who developed primary tumors with different localisation: bladder/bile ducts; rectum/pancreas; prostate/colon; prostate/sigma; sigma/stomach; palate/larynx+hypopharynx/tongue, respectively. Seventy five (9/12) of the patients had family history of cancer and 50% (6/12) early onset (<50y). Mutational screening was performed by NGS of a panel of 94 tumor-associated genes on MiSeq platform (Illumina).
A total of 82 variants were found of which 18.3% were evaluated as clinically significant. Among selected variants 33.3% (5/15) were pathogenic, 13.3% (2/15) likely pathogenic and 53.3% (8/15) variants of uncertain significance (VUSs). Pathogenic/likely pathogenic variants were detected in the genes BRCA1 (20%), MLH1 (13.3%), BRCA2 (6.7%) and CDH1 (6.7%) while VUSs in PMS1, GPC3, DIS3L2, PRF1, STK11, DICER1, RET, and MSH6, respectively.
Overall, the genetic cause of MPT was found in 58.3% (7/12) of the patients. Further research is needed to evaluate the functional effect of all VUSs.
Grants D-71/03.05.2018/MU-Sofia; KP-06-OPR03/1719.12.2018/NSF; DUNK01-2/2009/NSF, MES Bulgaria.
Medical University of Sofia.
Medical University Sofia; National Science Fund, Ministry of Education and Science, Bulgaria. Grants D-71/03.05.2018/MU-Sofia; KP-06-OPR03/1719.12.2018/NSF; DUNK01-2/2009/NSF, MES Bulgaria.
All authors have declared no conflicts of interest.