Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases

Dj. Peel et al., Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases, J NAT CANC, 92(18), 2000, pp. 1517-1522
Citations number
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Year of publication
1517 - 1522
SICI code
Background: The incidence of hereditary nonpolyposis colon cancer (HNPCC) i n the general population is not well defined because of the lack of large p opulation-based studies. We characterized the incidence of HNPCC in a large , population-based cohort of colorectal cancer probands and analyzed the lo cation of colorectal tumors. Methods: Of the participating 1134 probands fr om three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal c ancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and micr osatellite instability. All statistical tests were two-sided. Results: Amon g the probands diagnosed in Orange County during 1994 (population-based sam ple, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0.3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent w ith the Amsterdam criteria for HNPCC, Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showe d microsatellite instability. The family members of case subjects with muta tions tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of urete ral and endometrial cancers, were seen in both sets of families. The previo usly reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location re ported in the referral cases. Conclusions: On the basis of our data, we bel ieve that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previou sly reported characteristics of HNPCC, such as the proximal location of tum ors in the syndrome, may not always hold true in a population-based sample.