Colorectal adenomas were reported in 7,225 individuals; 1,457 with classic polyposis (100 adenomas or more) and 3,253 with attenuated (diminished) polyposis (20-99 adenomas). "The prevalence of pathogenic APC and biallelic [pertaining to both alleles (both alternative forms of a gene)] MUTYH mutations was 95 of 119 (80 percent) and 2 of 119 (2 percent), respectively, among individuals with 1,000 or more adenomas, 756 of 1,338 (56 percent) and 94 of 1,338 (7 percent) among those with 100 to 999 adenomas, 326 of 3,253 (10 percent) and 233 of 3,253 (7 percent) among those with 20 to 99 adenomas, and 50 of 970 (5 percent) and 37 of 970 (4 percent) among those with 10 to 19 adenomas. Adenoma count was strongly associated with a pathogenic mutation in multivariable analyses," the authors write.
The researchers note that their evaluation of individuals who underwent genetic testing because of a personal or family history suggestive of a familial polyposis syndrome suggests that genetic evaluation for APC and MUTYH mutations may be considered in individuals with 10 or more adenomas. "However, our results are derived from a selected cohort of high-risk individuals and need to be validated in larger populations of unselected patients."
"The mutation probabilities reported here may assist clinicians in their decision to recommend genetic evaluation and counsel patients undergoing genetic testing. However, it remains important to also consider the limitations of genetic testing at present, because one-third of patients with a classic familial adenomatous polyposis [FAP; a polyposis syndrome resulting from mutations in the APC gene characterized by multiple colorectal polyps] phenotype are found to not carry a mutation in either the APC or MUTYH gene. Such individuals should undergo periodic re-evaluation as other susceptibility genes are identified."
This study was supported by National Cancer Institute grants and by a National Institutes of Health grant.
"At this juncture, clinicians need to carefully consider the effect of a positive or negative test result on management of patient care prior to making decisions regarding genetic testing," wrote Hemant Roy, MD, and Janardan Khandekar, MD, of the NorthShore University HealthSystem, Evanston, Il., in an accompanying editorial.
"Appropriate patient education and informed consent prior to testing is mandatory, highlighting the integral nature of genetic counseling," the authors continued. "Until development of more robust genomic technologies for FAP detection, complementary approaches including careful assessment of family history and biomarkers may have utility. Furthermore, these considerations for FAP may serve as a model for evaluating the wider issues associated with practicing medicine at the front lines of the genomic revolution."
