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
"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.