Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

• Published in: Familial cancer 2020-07, Vol.19 (3), p.197-202
• Main Authors: Nguyen-Dumont, Tu, Steen, Jason A., Winship, Ingrid, Park, Daniel J., Pope, Bernard J., Hammet, Fleur, Mahmoodi, Maryam, Tsimiklis, Helen, Theys, Derrick, Clendenning, Mark, Giles, Graham G., Hopper, John L., Southey, Melissa C.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Cancer Research; Case-Control Studies; Cohort Studies; Colorectal cancer; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; DNA Mismatch Repair - genetics; DNA repair; DNA-Binding Proteins - genetics; Epidemiology; Female; Gene Expression Profiling - methods; Genes; Genetic disorders; Genetic Predisposition to Disease; Genetic screening; Germ-Line Mutation; Human Genetics; Humans; Mismatch repair; Mismatch Repair Endonuclease PMS2 - genetics; MLH1 protein; MSH2 protein; MSH6 protein; MutL Protein Homolog 1 - genetics; MutS Homolog 2 Protein - genetics; New South Wales; Pedigree; Population studies; Precision medicine; Registries - statistics & numerical data; Short Communication; Victoria; Yeast
• ISSN: 1389-9600; 1573-7292; 1573-7292
• DOI: 10.1007/s10689-020-00164-7

The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes ( MLH1 , MSH2 , MSH6 and PMS2 ) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4 MSH6 and 2 PMS2 ) and two in 833 control-families (0.2%, one each of MLH1 and MSH2 ). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.