SISE matters: the sum of information on seventy-yr-old equivalents measures pedigree information content when assessing the risk of HNPCC in a family
| Autor: | Roger C. Green, John R. McLaughlin, H. B. Younghusband |
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| Rok vydání: | 2004 |
| Předmět: |
Proband
Adult Male congenital hereditary and neonatal diseases and abnormalities Cancer Research medicine.medical_specialty Colorectal cancer Population Pedigree chart Sensitivity and Specificity Risk Factors Epidemiology Genetics medicine Humans Genetic Predisposition to Disease Family history education Genetics (clinical) Aged education.field_of_study Models Statistical business.industry Age Factors nutritional and metabolic diseases Middle Aged medicine.disease Penetrance Colorectal Neoplasms Hereditary Nonpolyposis digestive system diseases Human genetics Pedigree Oncology Female business Colorectal Neoplasms Demography |
| Zdroj: | Familial cancer. 4(2) |
| ISSN: | 1389-9600 |
| Popis: | Hereditary non-polyposis colon cancer (HNPCC) is a significant cause of colorectal and other malignancies. Due to the lack of features that reliably differentiate between a sporadic case and an inherited case of colon cancer, it is likely that HNPCC is under reported. The diagnosis of HNPCC relies heavily on finding multiple cases of colorectal or other specific cancers within a family. In the absence of a significant family history, a diagnosis of HNPCC is seldom considered. We postulate that small kinships--or, more specifically, kinships with a low information content--are more likely to be designated as having a low risk of an inherited cancer predisposition than are large kinships. This has the potential to exacerbate the under-diagnosis of HNPCC in small families, leading to inadequate treatment, follow-up and family counselling. We have developed an objective measure of the information content of individual pedigrees called the Sum of Information on Seventy-yr-old Equivalents (SISE) coefficient. The SISE coefficient is a function of the number of relatives in a kinship and their relationship to the proband, of their ages and of the age-dependent penetrance of HNPCC mutations. A population-based series of colorectal cancer cases was assessed, by currently accepted methods, for the likelihood of there being an HNPCC mutation segregating in each family. We observed that families with a low SISE coefficient were significantly more likely to be designated at low risk of HNPCC (Por =0.001). Using a cumulative binomial distribution function, we estimated the likelihood of observing multiple cancers in families of different SISE coefficients. |
| Databáze: | OpenAIRE |
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