Clinical-alimentary tractCancer Risk in Hereditary Nonpolyposis Colorectal Cancer Syndrome: Later Age of Onset
Section snippets
Cohort 1
Cohort 1 consisted of members from 45 HNPCC families in whom a germline mutation of MLH1 (N = 42) or MSH2 (N = 3) had been detected. The probands presented with CRC. They were accrued over a period of 15 years between 1980 and 1994 by 2 surgeons based on clinical data and family history. The patients came from a defined geographic area in southern and southeastern Finland. Their mutation status was determined by molecular genetic testing beginning in 1994. Of note, the ascertainment of most of
Age of Onset and LTR
The median age of diagnosis of CRC was 54.0 years among men and 70.0 years among women in the combined dataset (see Table 1 for 95% confidence intervals). For both sexes combined, the median age of diagnosis of CRC was 61.2 years. The mean age at diagnosis of CRC was 55.1 for men and 60.3 for women. These ages are approximately 10–15 years higher than the previous estimates of age at onset for CRC among HNPCC patients reported in the literature (see Discussion section). Men had an LTR estimate
Discussion
In our dataset, the age of onset of CRC in mutation-positive family members of the probands was remarkably much higher (55–60 y) than the age of onset found in probands from the same families (44–48 y). The age of onset in probands from these cohorts was the same as has been reported for HNPCC in previously published estimates (44–45 y). These findings can be explained in 3 ways. First, in Mendelian disorders probands potentially represent extreme examples of positive ascertainment bias, and
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Supported by grants CA67941 and P30 CA16058 from the National Cancer Institute.