Regular surveillance endoscopy may have value for patients with a family history of hereditary diffuse gastric cancer (HDGC), according to research.
"This study shows that careful and frequent endoscopic surveillance does have a role to play in evaluating the risk status for patients with a family history of diffuse gastric cancer that fulfills the criteria for hereditary diffuse gastric cancer," Dr. Rebecca C. Fitzgerald of the University of Cambridge, in the U.K., told Reuters Health by email.
"Patients with a germline mutation in the CDH1 (cadherin 1) gene need to carefully weigh the risks of delaying a risk-reducing gastrectomy," she advised.
As reported online July 6 in Gastrointestinal Endoscopy, Dr. Fitzgerald and her colleagues assessed the yields of signet-ring cell carcinoma foci in 85 adult patients from 46 families over roughly nine years. All patients had a family history of HDGC and were recruited from the Cancer Research UK Familial Gastric Cancer Registry.
The researchers evaluated each family over three generations and confirmed the family's HDGC status by histology. They compared the number of cancers detected in patients with and without a CDH1 variant by performing a series of endoscopies, doing visual inspections, and taking biopsies.
Before surveillance and at each endoscopy, the authors also gave participants the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30 and the 36-Item Short Form Health Survey (SF-36) questionnaire.
Based on 201 endoscopies, 54 patients tested positive for a CDH1 variant. Signet-ring cell carcinoma foci were found in 61% of the CDH1 patients during surveillance. By contrast, only 9.7% of the 31 patients who did not carry the mutation had such foci (p<0 .0005="" cancers="" endoscopies.="" fewer="" found="" later="" of="" on="" p="" these="" were="">
Participants found to have a CDH1 mutation were advised to undergo risk-reducing total gastrectomy. Patients who chose to delay surgery and those from families with no identified CDH1 variants were offered endoscopic surveillance, which was associated with improved psychological health.
Dr. Thomas P. Slavin of City of Hope in Duarte, California, told Reuters Health by phone, "Inherited cancer predisposition syndromes account for a very small subset - around 1% to 3% - of stomach cancer patients. But it's important for individuals in a larger sense because today, hundreds of thousands if not millions of people each year undergo hereditary germline testing for cancer predisposition of any kind, usually because a family member or they themselves have a cancer."
"Next-generation sequencing has catapulted the field of genetic cancer risk assessment," he explained. "In the past, we tested only one or two genes in individuals who might be most likely to have a personal or family history of cancer. Now, we're routinely testing 30 to 80 genes in more patients, and we almost always find the CDH1 gene. We find a lot of incidental CDH1 mutations in people who have genetic testing out of concern for some unrelated cancer and are surprised that they have a CDH1 mutation in their family."
"This is a very strong study by a very experienced group that has been doing this for a long time and has a very good track record," he said of the new research. "A strength is that they followed people for a long time so they have information over years and can make inferences of yield over time. The limitation is that it's a small study, but funding a large study would be difficult."