Patients who have had colorectal cancer and who are carriers of the DNA mismatch repair gene mutations that cause Lynch syndrome “have an increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers,” according to a study in the Journal of the National Cancer Institute.
Previous studies had shown that mutation carriers “are at a substantially increased risk of cancers of the colon, rectum, endometrium, stomach, ovary, ureter, renal pelvis, brain, small bowel, hepatobiliary tract, and pancreas,” the authors noted. A major inherited cancer syndrome, Lynch syndrome is also known as hereditary nonpolyposis colorectal cancer (HNPCC).
The study was based on data for 764 patients from the Colon Cancer Family Registry, evenly divided between men and women, who were carriers of the mismatch repair gene mutation and previously diagnosed with colorectal cancer. Most of the carriers (52%) were recruited in Australia and New Zealand, with 33% from the United States and 15% from Canada. The average age at diagnosis of colorectal cancer was 44 years.
Compared with the general population, following colorectal cancer, carriers of mismatch repair gene mutations had a 70-fold increased risk for cancer of the small intestine, a 13-fold increased risk for cancer of the kidney, renal pelvis, and ureter or urethra, a 7-fold increased risk for cancer of the bladder, a 6-fold increased risk for hepatobiliary tract cancer, and a nearly 6-fold increased risk for gastric cancer. Men had a 2-fold increased risk of prostate cancer. The most common primary cancer following colorectal cancer for women with Lynch syndrome was endometrial cancer, with a 40-fold increased risk compared to the general population. There were 20 breast cancers and 6 ovarian cancers in the study population.
“These new data provide further determination of cancer risks, potentially informing and justifying ongoing studies to create the evidence for effective screening methodologies and intervals in [mismatch repair] gene mutation carriers,” the researchers concluded. “Larger studies are needed to refine risk estimates separately for specific [mismatch repair] gene mutations to best inform policies on clinical risk management.” ■
Win AK, et al: J Natl Cancer Inst 104:1363-1372, 2012.