Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk

Abstract

CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.

The effect of genotypes and parent of origin on cancer risk and age of cancer development in PMS2 mutation carriers

“…Cancer risks associated with PMS2 are lower than those reported for MLH1 and MSH2. 1,3 Phenotypes resulting from germ-line MMR gene mutations vary both among and within families. 4 Interfamilial variance might be partly attributable to known genotype-phenotype Purpose: Lynch syndrome (LS), a heritable disorder with an increased risk of primarily colorectal cancer (CRC) and endometrial cancer (EC), can be caused by mutations in the PMS2 gene.…”

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

“…1) (Aarnio et al, 1999;Abdel-Rahman et al, 2006;Grover et al, 2009;Hampel et al, 2005;Vasen et al, 2007;Vasen et al, 2001b). This risk varies depending both on the affected MMR gene and on the gene loci involved (Plaschke et al, 2004;ten Broeke et al, 2015;Vasen et al, 2001a;Wijnen et al, 2009). To facilitate genetic counselling and clinical practice, an interactive website providing the complete distributions of all cancer types, depending on gene defect, from any age is now available at is available at http://www.lscarisk.org .…”

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

“…Moreover, as the commonly known technical difficulties of analyzing PMS2 are slowly being overcome by new analysis strategies [41][42], critically needed evidence concerning the role of PMS2 can be expected. For instance, recently, ten Broeke et al reported a standardized incidence ratio of 3.8 for breast carcinomas, which led them to suggest adding mammography from age 40 years in PMS2 families with evident clusters of BC [43]. Finally, one mutation was found in SUFU, and considered an incidental finding given the absence of a personal or family history of medulloblastoma or Gorlin syndrome.…”