Cancer risk patterns in Lynch syndrome differ by path_MMR variants

Last Updated: 2017-08-09

By Will Boggs MD

NEW YORK (Reuters Health) - Carriers of different path_MMR variants (Lynch syndrome) show different patterns of cancer risk and survival, according to findings from the Prospective Lynch Syndrome Database (PSLD).

While "in the past most patients with Lynch syndrome died from their first cancer in early or middle adult life," the new data show that "close to all identified pathogenic-gene carriers were cured from these cancers due to close surveillance aiming at early detection and treatment," said Dr. Pal Moller from Oslo University Hospital in Norway.

"In contrast to ovarian cancer associated with breast cancer, ovarian cancer in Lynch syndrome had good prognosis when early treated," he told Reuters Health by email.

Lynch syndrome includes germline pathogenic variants in any of four DNA MMR genes: path_MLH1, path_MSH2, path_MSH6, and path_PMS2. There is a paucity of information about the cancer risks associated with individual variants.

Dr. Moller and colleagues used PSLD data from 3,119 patients to compare cancer risk and survival patterns according to path_MMR variants.

Overall, 813 cancers were diagnosed in 618 patients, the team reports in Gut, online July 28.

The cumulative incidence at 75 years for any cancer was 76% for path_MLH1, 80% for path_MSH2, and 61% for path_MSH6.

Carriers of path_MLH1 had lifetime incidences of 46% for colorectal cancer, 43% for endometrial cancer, 10% for ovarian cancer, 21% for upper gastrointestinal tumors, 8% for urinary tract cancers, and 17% for prostate cancer.

For path_MSH2 carriers, the incidences were 43% for colorectal cancer, 57% for endometrial cancer, 17% for ovarian cancer, 10% for upper gastrointestinal tumors, 25% for urinary tract cancers, and 32% for prostate cancer.

For path_MSH6 carriers, they were 15% for colorectal cancer, 46% for endometrial cancer, 13% for ovarian cancer, 7% for upper gastrointestinal tumors, 11% for urinary tract cancers, and 18% for prostate cancer.

Compared with the general population, the relative risk of any cancer was 3.1 for path_MLH1, 3.3 for path_MSH2, and 2.5 for path_MSH6.

"Cancer risk in carriers of pathogenic variants of PMS2 was too low to be determined," Dr. Moller said. "Pathogenic variants of PMS2 should not be considered a cause of a dominantly inherited disorder."

For each cancer, five- and 10-year survival rates differed but were generally good for colon cancer, endometrial cancer, ovarian cancer, urinary tract cancer and prostate cancer, and poor for gallbladder and pancreatic cancer.

"All results are open-access available at our website, www.lscarisk.org, where the detailed results may be tailored to each single patient's gene, gender, and age to select properly adapted health care modalities tailored to each single patient," Dr. Moller said. "This is made to inform not only the health care providers, but also to enable both the patients and the broad public to make informed decisions on (one's) own life/future with respect to selecting genetic testing and which health care modalities to choose if testing demonstrate a disease-causing genetic variant."

"Clinical guidelines for health care to Lynch syndrome patients are currently being revised based on our findings," he added.

SOURCE: http://bit.ly/2vExSu6

Gut 2017.