Current Research Projects of the Hereditary Diffuse Gastric Cancer Research Team at the British Columbia Cancer Agency.
David Huntsman, Pardeep Kaurah
Over the last 10 years, we have learnt a lot about hereditary diffuse gastric cancer (HDGC). However, there are still many critical knowledge deficits which need to be addressed to improve the cancer control of families with known CDH1 mutations and to inform the care of families with strong histories of gastric cancer of whom known mutations have been identified.
Our research team is both collaborating with other members of the International Gastric Cancer Linkage Consortium (IGCLC) to develop a more accurate understanding of the cancer risks associated with carrying CDH1 mutations, and is performing research locally that should help our global research community move forward.
Studies we are actively engaged in include:
1) The identification of gastric cancer associated mutations in families who do not have the traditional CDH1 mutations. In these studies, we are looking for a mutation outside of the coding region of the CDH1 gene and using novel technologies to identify regions in other genes.
2) The role of CDH1 in hereditary breast cancer. In this large study which is nearly completed, Dr. Intan Schrader, a geneticist in training working with our team, has studied CDH1 in almost 400 families with a history of lobular breast cancer. So far it appears that CDH1 mutations are rare in families which have breast cancer but no history of gastric cancer. The results of this study will help to form testing guidelines for women with lobular breast cancer and a family history of breast and/or stomach cancer.
3) Quality of life post-prophylactic gastrectomy. Pardeep Kaurah, the genetic counselor who has worked with most of the families we have tested in British Columbia, is now completing her PhD studies. The project she has selected is the study of the quality of the life post-prophylactic gastrectomy. We hope that through this work we will obtain a better sense of the pertinent clinical and pychosocial information that should be provided to individuals who are considering prophylactic gastrectomy. These would include any indicators that could be used to predict who would fare poorly after this procedure. Until we have a more effective screening tool for hereditary diffuse gastric cancer, prophylactic gastrectomy would appear to be a useful cancer-risk reduction strategy. Therefore studying the consequences of this procedure is relevant.
Through these studies, our international collaborations and our ongoing interaction with HDGC families, we will continue to formulate new questions to be answered and endeavor to contribute new knowledge that will help in the management of individuals who carry CDH1 mutations.
My husband’s two brothers died of HDGC in their 40s, one of which took part in your Hereditary Diffuse Gastric Cancer research study in 2007, but did not carry a known mutation. Dr. Huntsman made a comment, that although a mutation was not identified “given the strong family history of diffuse gastric cancer in two half-siblings at young ages, this family is very suspicious for clinical Hereditary Diffuse Gastric Cancer.” We have not done any genetic testing as our health insurance does not cover genetic testing. It appears you are studying associated mutations in families who do not have the traditional CDH1 mutation. How can my husband take part in this study? My husband’s brother who took part in the study’s name was Edward Treseler.
HI Pat,
Your question is certainly an important and pertinent one for families such as your husband’s. Our lab is in the very early stages of exploring other genetic regions of interest in this condition. However, we are not at the point where we are testing individuals for these regions. I suggest that either you or your husband contact us in the next year to see where we are with this direction of testing.
Although it took some time and increased technology, I was found to have a mutation at CDH1 by your lab. I did have 2 primary gastric cancers 1992 and 1997 last one resulting in TG. Oct 2008 I had bilateral propylactic mastectomies due to my concerns of lobular breast cancer and poor tolerance of tamoxifen and evista. I did have multiple sites of atypical lobular hyperplasia on pathology so I made the right decision. My question is if colon cancer frequency is increased in our population.
Thank you.
Hi Christine,
An excellent question. Although there have been reports of signet-ring colon cancer in a few families with germline CDH1 mutations, we still do not have enough evidence to recommend colon cancer screening in all HDGC families. In HDGC families in which there is a family history of colon cancer, (especially the signet-ring subtype), intense colon cancer screening is strongly recommended. Therefore, at this point in time the families should be judged on a case-by-case basis.
Whether germline CDH1 mutation carriers are at higher risk of other cancers still remains to be seen.
Dear Pardeep,
When you say that “intense colon cancer screening” is strongly recommended in HDGC families with family history of colon cancer, is there a recommendation for how frequently to have the screening done?
My family has a CDH1 mutation and we also have family history of colon cancer. Since 2003, I have been having colonoscopies every couple of years. I’m not sure how frequently other family members are having screening done (if at all).
Thanks!
In my family we have HDGC on my mother’s side and some colon cancer on my father’s side. My gastroenterologist is recommending colonoscopy screenings every two years for me, although I’m 51. I don’t know what his recommendation would be for younger family members.