Authors: Hollie Franklin
A study published recently online in JAMA Oncology suggests that more precise age-associated risks of gastric and breast cancer can be determined for carriers of the CDH1 gene mutation. The team believes that the findings may assist with genetic counseling and management of at-risk individuals from CDH1-positive hereditary diffuse gastric cancer (HDGC) families.
Currently, the cumulative lifetime risk of gastric cancer in CDH1 carriers is determined from a small number of families, with predictions of risk ranging from 40–67% in men and 63–83% in women. Women carriers also have a breast cancer risk of between 39 and 52%. The currently recommended methods employed to reduce the risk of gastric cancer are screening gastroscopy with multiple random biopsies or surgical removal of the entire stomach.
In this present research, David G Huntsman (British Columbia Cancer Agency, Canada) and co-authors tested 183 new families with HDGC for CDH1 germline mutations. Penetrance was determined from 3858 individuals from 75 mutation-positive families from this study and other study groups. To determine if additional genes are associated with HDGC, germline DNA from 144 HDGC families that did not carry the CDH1 mutation was also screened for 55 other cancer-associated genes.
Thirty one distinct CDH1 mutations, 14 of which were novel, in 34 of the 183 families (19%) were found. The researchers estimate that by the age of 80 years, the cumulative incidence of gastric cancer is 70% for men and 56% for women (and a 42% risk of breast cancer in women). Candidate mutations were also identified in 16 out of 144 probands, including mutations within genes of high and moderate penetrance. .
In a related editorial, James M Ford (Stanford University School of Medicine, CA, USA) suggested: “These updated risk assessments should be considered the new standard for genetic counseling and will be included in the next International Gastric Cancer Linkage Consortium guidelines.” He concluded: “The current article by Hansford et al. provides a major advance. Further clinical and genetic research is necessary to identify biomarkers and better methods of screening individuals at high risk.”
Source: Hansford S, Kaurah P, Li-Chang H et al. Hereditary diffuse gastric cancer syndrome. JAMA Oncol. doi:10.1001/jamaoncol.2014.168 (2015) (Epub ahead of print); Ford JM. Hereditary gastric cancer. JAMA Oncol. doi: 10.1001/jamaoncol.2014.187 (2015) (Epub ahead of print). JAMA Oncology press release