The prevalence of germline pathogenic variants in Estonian colorectal cancer patients: results from routine clinical setting 2016-2021

Laura Roht; Mikk Tooming; Kadri Rekker; Hanno Roomere; Kadri Toome; Ülle Murumets; Ustina Šamarina; Katrin Õunap; Tiina Kahre

doi:10.3389/fgene.2022.1020543

The prevalence of germline pathogenic variants in Estonian colorectal cancer patients: results from routine clinical setting 2016-2021

Front Genet. 2022 Nov 8:13:1020543. doi: 10.3389/fgene.2022.1020543. eCollection 2022.

Authors

Laura Roht^{1

2}, Mikk Tooming^{1

3}, Kadri Rekker³, Hanno Roomere³, Kadri Toome³, Ülle Murumets³, Ustina Šamarina³, Katrin Õunap^{1

2}, Tiina Kahre^{1

3}

Affiliations

¹ Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
² Department of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
³ Department of Laboratory Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer in Estonia in both women and men. According to the Estonian National Institute for Health Development, in 2017, there were 357 new colon cancer only cases in women and 282 in men. For colorectal cancer, the number for men and women altogether was 1040 in the same year. In 2018, there were over 1.8 million new cases worldwide. The Mayo Clinic found in a prospective, two-year multi-site study of CRC patients that 15.5% of patients carried pathogenic germline variants (PGV), using an >80 gene Next Generation Sequencing (NGS) panel. Material and methods: This retrospective study aimed to analyse the estimated prevalence of pathogenic/likely pathogenic germline variants in Estonian colorectal cancer patients using NGS in a routine clinical setting. We gathered five-year data (July 2016-July 2021) of colorectal cancer patients (mostly not selected for age or family history) tested with either Illumina TruSight Cancer (94 genes) or TruSight Hereditary Cancer (113 genes) NGS panels. Results: Three hundred and fourteen NGS analyses were performed due to either CRC or polyposis in anamnesis and/or family anamnesis, including 126 CRC cases and 44 colorectal polyposis cases, while 144 were either healthy family members or had other types of cancers. While a known disease-causing variant was identified in 16.4% of all cancer patients tested, we found that 21.4% of CRC patients had such a variant. Among the 44 colorectal polyps cases MLH1, gene was the most affected one (25%), the second and third most affected genes were MSH2 and CHEK2. Other genes with disease-causing variants found in CRC patients included APC, BLM, BMPR1A, BRCA1, FANCM, MSH6, MUTYH, PMS2, SMAD4, SPINK1 and VHL. Conclusion: Our result give an overview of genetic testing of CRC patients, the prevalence of disease-causing variants and their landscape in Estonia. According to Estonian data, only 2.7-6.1% of CRC patients are genetically tested, which is around ten times less frequently than breast cancer patients and their family members. The diagnostic yield of CRC patients is 21.4%, suggesting that genetic testing will likely improve timely diagnosis and outcomes.

Keywords: NGS; colorectal cancer; hereditary cancer syndromes; molecular genetics of CRC; routine clinical setting diagnostics.