Grant Number:	5R01CA098438-03 Interpret this number
Primary Investigator:	Begg, Colin
Organization:	Sloan-Kettering Inst Can Research
Project Title:	Epidemiologic Parameters of Rare Cancer Risk Factors
Fiscal Year:	2005

DESCRIPTION (provided by applicant): In recent years several major cancer genes have been identified. Typically, mutations in these genes are rare in the population, but they confer a substantially increased risk to carriers. Estimation of their population epidemiologic characteristics, such as relative risks and penetrances, is challenging, primarily because of their rarity. As a result, various novel designs and analytic techniques have been proposed and utilized to estimate these parameters indirectly. The general goal of this revised proposal is to critically evaluate the statistical properties of these methods, to compare different approaches, and to develop new methods as needed. The first aim will focus on penetrance estimation. We will examine the kin-cohort design, when probands have been identified from incident cases, a configuration known to result in upward bias, with a view to developing techniques for bias correction. Also we will study the derivation of penetrance from comparing carrier frequencies in patients with second primaries with patients with first primaries, an approach that does not depend on family histories of cancer. We will endeaver to use these results develop risk predictions that allow for risk adjustment on the basis of known family history of cancer. In the second aim we will build on the design that utilizes first and second primaries to estimate relative risks. The goals here will be to identify and correct the impact of potential survival bias (length biased sampling of second primaries if the gene is associated with survival), to modify analyses for the impact of individuals who qualify as both cases and controls in this study design, and to examine the impact of unknown risk factors that interact with the genotype of interest. All of these aims are motivated by an international study of the genetic epidemiology of melanoma that is currently in progress.




Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death.
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Sex-Specific Associations of MDM2 and MDM4 Variants with Risk of Multiple Primary Melanomas and Melanoma Survival in Non-Hispanic Whites.
Authors: Ward S.V. , Autuori I. , Luo L. , LaPilla E. , Yoo S. , Sharma A. , Busam K.J. , Olilla D.W. , Dwyer T. , Anton-Culver H. , et al. .
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Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study.
Authors: Davari D.R. , Orlow I. , Kanetsky P.A. , Luo L. , Busam K.J. , Sharma A. , Kricker A. , Cust A.E. , Anton-Culver H. , Gruber S.B. , et al. .
Source: Current Oncology (toronto, Ont.), 2021-11-16 00:00:00.0; 28(6), p. 4756-4771.
EPub date: 2021-11-16 00:00:00.0.
PMID: 34898573
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Disease-Associated Risk Variants in ANRIL are Associated with Tumor-Infiltrating Lymphocytes Presence in Primary Melanomas in the Population-Based GEM Study.
Authors: Davari D.R. , Orlow I. , Kanetsky P.A. , Luo L. , Edmiston S.N. , Conway K. , Parrish E.A. , Hao H. , Busam K.J. , Sharma A. , et al. .
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PMID: 34607836
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Differences in Melanoma Between Canada and New South Wales, Australia: A Population-Based Genes, Environment, and Melanoma (GEM) Study.
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Authors: Wood R.P. , Heyworth J.S. , McCarthy N.S. , Mauguen A. , Berwick M. , Thomas N.E. , Millward M.J. , Anton-Culver H. , Cust A.E. , Dwyer T. , et al. .
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Association of IRF4 single-nucleotide polymorphism rs12203592 with melanoma-specific survival.
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Inherited Melanoma Risk Variants Associated with Histopathologically Amelanotic Melanoma.
Authors: Gibbs D.C. , Orlow I. , Vernali S. , Powell H.B. , Kanetsky P.A. , Luo L. , Busam K.J. , Sharma A. , Kricker A. , Armstrong B.K. , et al. .
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PMID: 31568773
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A risk prediction model for development of subsequent primary melanoma in a population-based cohort.
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PMID: 31520533
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Relationship of Chromosome Arm 10q Variants to Occurrence of Multiple Primary Melanoma in the Population-Based Genes, Environment, and Melanoma Study.
Authors: Miles J.A. , Orlow I. , Kanetsky P.A. , Luo L. , Cust A.E. , Armstrong B.K. , Kricker A. , Anton-Culver H. , Gruber S.B. , Gallagher R.P. , et al. .
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Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.
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Associations of MC1R genotype and patient phenotypes with BRAF and NRAS mutations in melanoma.
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Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma.
Authors: Vernali S. , Waxweiler W.T. , Dillon P.M. , Kanetsky P.A. , Orlow I. , Luo L. , Busam K.J. , Kricker A. , Armstrong B.K. , Anton-Culver H. , et al. .
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No association between prediagnosis exercise and survival in patients with high-risk primary melanoma: A population-based study.
Authors: Schwitzer E. , Orlow I. , Zabor E.C. , Begg C.B. , Berwick M. , Thomas N.E. , Kanetsky P.A. , Jones L.W. , GEM Study Group .
Source: Pigment Cell & Melanoma Research, 2017 Jul; 30(4), p. 424-427.
EPub date: 2017-06-08 00:00:00.0.
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Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas.
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CDKN2A germline mutations in individuals with cutaneous malignant melanoma.
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Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample.
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