Annals of Oncology 15:598-604, 2004
© 2004 European Society for Medical Oncology
Original Paper |
Familial risk of endometrial cancer after exclusion of families that fulfilled Amsterdam, Japanese or Bethesda criteria for HNPCC
Received 29 September 2003; revised 2 December 2003; accepted 22 December 2003Background:
Endometrial cancer is the second most common lesion within hereditary non-polyposis colorectal cancer (HNPCC) syndrome. The importance of the non-HNPCC genetic predisposition to endometrial cancer is unclear, and the familial aggregation of endometrial cancer after exclusion of HNPCC families may offer valuable clues about the involvement of non-HNPCC-related genes.
Patients and methods:
The families of the nationwide Swedish Family-Cancer Database were classified as HNPCC families according to the Amsterdam I or II, the modified Amsterdam, the Japanese and the Bethesda criteria. Standardized incidence ratios (SIRs) for endometrial cancer when parents or siblings were diagnosed with cancer at the most common sites were calculated before and after exclusion of HNPCC families.
Results:
The proportion of individuals in the families with endometrial cancer was highest when the criteria required three cancers within a family or multiple HNPCC-related cancers in the same individual. Consideration of the Amsterdam or the Japanese criteria hardly reduced the familial aggregation of endometrial cancer. After exclusion of families that fulfilled the Bethesda criteria, SIRs were significant when the parents were diagnosed with endometrial or thyroid gland cancers; 75.7% (95% confidence interval 60% to 99.1%) of the familial cases of endometrial cancer were not related to HNPCC according to the Bethesda criteria. The reduction of SIRs for cancers at the colon, pancreas, prostate and ovary was limited when the Bethesda criteria were applied. However, the Bethesda criteria identified most of the familial aggregation when endometrial cancers were diagnosed before the age of 55 years.
Conclusions:
The data suggest that additional effects, not related to HNPCC, contribute to the familial aggregation of endometrial cancer.
1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 2 Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden
Key words: Amsterdam criteria, Bethesda guidelines, endometrial cancer, familial risk, HNPCC, Japanese criteria
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