Familial aggregation of tumors and detection of hereditary non‐polyposis colorectal cancer in 3‐year experience of 2 population‐based colorectal‐cancer registries

Abstract

The clinical data of 2 population-based registries, located in areas with different incidence rates of colorectal cancer, were used in order to assess the role of familial factors in the pathogenesis of these tumors. The occurrence of tumors in family members was investigated in 389 subjects with colorectal cancer registered in Modena (Northern Italy, an area characterized by a high incidence of colorectal malignancies) between 1984 and 1986; similar information was obtained in 213 patients with tumors of the large bowel registered in Ragusa (Sicily, Southern Italy, an area of similar magnitude and with low incidence rates for these tumors) in the 3-year period 1988 to 1990. In both series, colorectal cancer occurred significantly more often among relatives of patients. Controls were patients of the same sex and age (+/- 5 years) hospitalized during the study periods, but not for gastrointestinal or neoplastic diseases. There were 89 cancer cases (3.1%) among 2,851 relatives of patients in Modena, vs. 17 cases among 1,744 relatives (1.0%) in Ragusa (p < 0.01). Apart from colorectal cancer, there was no excess of other types of tumors in patients' families (in both series). During the 3 years of registration, 17 cases of hereditary non-polyposis colorectal cancer (HNPCC, or Lynch syndrome) were diagnosed in Modena; in contrast, this syndrome was more rare in Ragusa (one case only during 3 years of observation). Similarly, many more families with clinical suspicion of HNPCC were recorded in Northern regions (44 vs. 10). Although incidence rates of colorectal cancer are appreciably higher in Northern than in Southern Italian regions, the excess of this cancer type among close relatives is similar. However, full-blown HNPCC or suspected Lynch syndrome were significantly more frequent in Northern Italy.

Aberrant crypt foci in patients with colorectal cancer

“…No difference in ACF density was observed according to gender, in agreement with colorectal cancer incidence in men and women, as reported in the cancer registries of Ragusa and Modena (Modica et al, 1995). On the other hand, age-specific incidence rates for large bowel cancer show a sharp increase from 65 years onwards in both registries.…”

“…ACF density in Modena was significantly higher than in Ragusa, and approached figures previously reported in colon cancer patients from Canada, USA and Japan (Roncucci et al, 1991a;Pretlow et al, 1994;Yamashita et al, 1995). This pattern reflects colorectal cancer incidence rates in the two Italian provinces (Modica et al, 1995). Experimental evidence supports the view that density of ACF is strictly related to initiation in colon carcinogenesis (McLellan and Bird, 1988).…”

“…In Italy, incidence rates for colon and rectal cancer show wide variations according to data of local cancer registries. In Modena (Northern Italy) they are in the order of 50-65 new cases per 100 000 residents per year, whereas in Ragusa, Sicily (Southern Italy), they are about half (25-30 new cases) (Zanetti and Crosignani, 1992;Ponz de Leon et al, 1993;Modica et al, 1995).…”

Family history of cancer and risk of colorectal cancer in Italy

“…As in hereditary syndromes involving CRC, such as, for instance, HNPCC, an excess of a variety of other cancers has also been reported, conceivably the weak increase in risk observed may be real. Mortality rates for cancer of the intestine are much lower in the south of Italy than in the north (La Vecchia and Decarli, 1986), and the frequency of HNPCC is also notably lower in the south (Modica et al, 1995). In our study, however, the risk of family history of intestinal cancer was consistent across various geographical areas and, if anything, tended to be higher in the two centres from southem Italy (Latina and Naples), particularly for colon cancer.…”

“…The frequency of susceptibility genes varies in different populations. Even within Italy, the search for HNPCC families in two cancer registries, one in the north of the country and the other in the south, has brought to light an apparently different frequency of the disease in the two areas (Modica et al, 1995).…”