Lynch syndrome and Breast Cancer Risk Association (ISU Student Post)

Post by Jessica Cabotaje (Indiana State University Genetic Counseling Student)


One of the most important (and in my opinion, one of the most difficult) skills genetic counselors must develop is the ability to analyze and interpret a patient’s family history. In cancer counseling, we see breast and ovarian cancer in a family and think BRCA1/2.  We hear colon and endometrial cancer and think Lynch syndrome.  However, a study published in Nature last month may add a new association.  The study conducted by Roberts et al., suggests that pathogenic mutations in MSH6 and PMS2, two genes associated with Lynch syndrome, may also lead to increased risks for breast cancer.


Past studies on this topic have been inconsistent, with some showing increased risk and others showing none. Unlike previous studies, in which the majority of people had mutations in MLH1 or MSH2, the study conducted by Roberts et al. included patients with mutations in each of the four Lynch syndrome genes.  They also broke down breast cancer risk by gene, rather than the risk for the group of Lynch genes.  Individuals who had pathogenic or likely pathogenic variants in one of the Lynch genes were identified from a group of more than 50,000 women who had multigene cancer panels.  The incidence of breast cancer in those with Lynch gene mutations was then compared to the expected population incidence.  According to the paper, “MSH6 and PMS2 were found to confer 31.1% and 37.7% cumulative risks for breast cancer by the age of 60 while PVs in MLH1 or MSH2 were found to confer breast cancer risks close to the expected general population risk, 16.1% and 15.5%, respectively.”


This study has important implications for cancer genetic testing. The women in this study with mutations in MSH6 and PMS2 were more likely to meet BRCA1/2 criteria than Amsterdam criteria, and 11% had no personal or family history of the cancers traditionally associated with Lynch syndrome.  If future studies confirm the findings of this paper, it may become routine to offer testing for Lynch genes for histories of breast cancer. This also highlights the question of single gene vs. small panel vs. large panel testing strategies.  The women in this study were found because they had large panels that may have included genes not traditionally thought to be associated with the cancers in their families.  Oftentimes, even if a genetic counselor decides to order a larger panel, they order only genes that are relevant to the history.  Although panels for breast and gynecological cancers include the Lynch genes, panels for breast cancer only typically do not.


As more studies are conducted, there is no doubt that we will continue to learn more about the associations between genes and cancer risks. It will be interesting to see how clinical practice and testing strategies change as new discoveries are made.



Roberts, M., Jackson, S., Susswein, L., Zeinomar, N., Ma, X., Marshall, M., Stettner, A., Milewski, B., Xu, Z., Solomon, B., Terry, M., Hruska, K., Klein, R. and Chung, W. (2018). MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer. GENETICS in MEDICINE.

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