Population-Calibrated Gene Characterization: Estimating Age at Onset Distributions Associated With Cancer Genes.

Journal of the American Statistical Association
Edwin S Iversen, Sining Chen

Abstract

Phenotypic characterization of rare disease genes poses a significant statistical challenge, but the need to do so is clear. Clinical management of patients carrying a disease gene depends crucially on an accurate characterization of the genetically predisposed disease, including its likelihood of occurrence among mutation carriers, natural history, and response to treatment. We propose a formal yet practical method for controlling for bias due to ignoring ascertainment, defined as the sampling mechanism, when quantifying the association between genotype and disease using data on high-risk families. The approach is more statistically efficient than conditioning on the variables used in sampling. In it, the likelihood is adjusted by a factor that is a function of sampling weights in strata defined by those variables. It requires that these variables and the sampling probabilities in the strata they define either are known or can be estimated. The latter requires a second, population-based dataset. As an example, we derive ascertainment-corrected estimates of penetrance for the breast cancer susceptibility genes BRCA1 and BRCA2. The Bayesian analysis that we use incorporates a modified segregation model and prior data on penetran...Continue Reading

References

Sep 1, 1988·American Journal of Epidemiology·J M Schildkraut, W D Thompson
Dec 1, 1986·Theoretical Population Biology·W J Ewens, N C Shute
Mar 12, 1987·The New England Journal of Medicine·UNKNOWN Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Dev
Jan 1, 1985·Journal of Chronic Diseases·R R LoveD M Josten
Jan 1, 1971·Human Heredity·R C Elston, J Stewart
Oct 1, 1995·British Journal of Cancer·D Ford, D F Easton
Jan 1, 1994·Genetic Epidemiology·W J Gauderman, D C Thomas
May 15, 1997·The New England Journal of Medicine·J P StruewingM A Tucker
Mar 7, 1998·American Journal of Human Genetics·G ParmigianiO Aguilar
Jun 16, 2000·Journal of the National Cancer Institute. Monographs·D C Thomas
Feb 22, 2002·British Journal of Cancer·A C AntoniouD F Easton
Mar 7, 2002·American Journal of Human Genetics·Michael P EpsteinMichael Boehnke
Jun 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Donald A BerryGiovanni Parmigiani
Aug 22, 2002·Journal of the National Cancer Institute·Colin B Begg
Oct 18, 2002·Genetic Epidemiology·David V Glidden, Kung-Yee Liang

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Citations

Feb 18, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sining ChenGiovanni Parmigiani
Oct 2, 2020·Genetic Epidemiology·Margaux L A HujoelDanielle Braun
Sep 6, 2019·Journal of the American Statistical Association·Seung Jun ShinWenyi Wang
Mar 31, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Edwin S IversenAlvaro N A Monteiro

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