BUFFALO, NY--New analysis of familial colorectal cancer data suggests that the disease is not associated with genetic anticipation--the earlier onset of disease in successive generations--said Gloria M. Petersen, PhD, at the Eighth Annual Meeting of the ICG-HNPCC (International Collaborative Group-Hereditary Nonpolyposis Colorectal Cancer).
"The study shows that a cohort effect is responsible for the apparent observation of genetic anticipation in this disease," she said, "and that when the data are corrected for this bias, there is no statistical trend toward earlier age of onset in succeeding generations."
Dr. Petersen, associate professor of epidemiology, and her colleagues at the Johns Hopkins School of Hygiene and Public Health analyzed data from family history questionnaires from the Johns Hopkins Hereditary Colorectal Cancer Registry. Of 588 kindreds (1,293 patients), 400 parent/offspring pairs in 260 pedigrees had complete information regarding age of diagnosis.
The 400 pairs were divided by their birth year into three cohorts: persons born before 1921, between 1921 and 1930, and after 1930. The analysis showed that the offspring and parents in the first age group were diagnosed at ages 64 and 65, respectively; in the second age group, at ages 57 and 66; and in the third age group, at ages 44 and 61.
"The expected cohort effect was observed among the offspring in the latter two groups. However, in the cohort of subjects born before 1921, a group that had the same window of risk, we observed no statistical difference between parents and offspring," Dr. Petersen said. Further analysis of the cohort born before 1921, by pairwise comparison and life table analysis, again showed no difference in age at diagnosis.
The researchers also analyzed two subgroups--52 parent/offspring pairs from 29 families who met the ICG criteria for hereditary nonpolyposis colorectal cancer (HNPCC) and 14 parent/offspring pairs from seven families with known germline mutations of DNA mismatch repair genes.