Tuesday, March 14, 2017

More About CDH1

The E-Cadherin gene or CDH1 is a tumor suppressor protein that maintains tissue integrity as it mediates cell-cell adhesion. It helps to regulate cells so that they don’t grow out of control or grow too rapidly.  For those who care, the CDH1 gene is located on chromosome 16q22.1 and it contains 2.6 kb of coding sequences with 16 exons.

In 1998, Dr. Parry Guilford first linked inherited mutations in the CDH1 gene with familial gastric cancer in three Maori families in New Zealand.  Many subsequent studies have been done and published papers can be found online.  Depending on your biological and medical knowledge, some are easier to read than others.  Because this is such a rare mutation, many of the studies have very small sample sizes and with each new study, the results change, sometimes considerably.

My gene mutation is c.2287G>T.  It is a nonsense truncation in Exon 14.  My results, dated May 22, 2015, indicate a 80% cumulative risk of diffuse gastric cancer by age 80 for both men and women, as well as a 39%-52% risk of lobular breast cancer for women.  There also may be an increase risk for colon cancer, but no percentage was listed in my test results.  In updated clinical guidelines, found in several articles online published February-May 2015, the cumulative risk for diffuse gastric cancer by age 80 is listed as 70% for men and 56% for women and the risk of lobular breast cancer is listed as 42%.  According to those guidelines, there is currently no evidence that the risk of other cancers is significantly increased in individuals with a CDH1 mutation.

Whether the risk is 80% or 56%, or something in between, the risk is high when you are talking about your life.  The recommendation of all the studies is that individuals who tested positive for a CDH1 mutation should consider prophylactic gastretomy regardless of other screening.  However, if the individual chooses not to have the gastrectomy or delays the gastrectomy, annual upper endoscopy is recommended with a minimum of 30 random biopsies.  However, the literature goes on to say that because of the very focal nature of these endoscopically invisible lesions, it is quite possible that they will not be detected by random biopsies.  So have the endoscopy, but more than likely, it won't find anything.

In almost 100% of the cases where a prophylactic total gastrectomy has been performed because of a CDH1 mutation, signet-ring cell carcinoma has been found in the pathology after the surgery, meaning that the patients are considered to have Stage 1 cancer.  However, because it is early stage and contained within the stomach, the surgery is curative and no further treatments are needed.

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