title: Estimating the relative risk of developing melanoma in INK4A carriers.
abstract: Estimation of the relative risk of cancer due to rare germline mutations using population-based epidemiological techniques is challenging, since studies with very large numbers of subjects are required. In this pilot study using a novel study design, we evaluated the role of INK4A mutations in melanoma by comparing patients with multiple primary melanomas to those with single primaries. Patients were ascertained from the Surgery and Dermatology Clinics at Memorial Sloan-Kettering Cancer Center and at the Yale University Pigmented Lesion Clinic. Subjects completed a questionnaire covering risk factors for melanoma and were tested for INK4A mutations. Five (8%) of 65 patients with multiple primaries had a mutation, compared with none of 88 patients with single primaries (P=0.03). Examination of other factors, such as number of nevi on the arms of the patients, fair skin, hair and eye colour, and other phenotypic characteristics associated with the risk of melanoma, demonstrates that these factors exhibit higher prevalence in the multiple primary cases than in the single primaries. These results provide evidence of the utility of the new study design in evaluating the impact of rare but highly penetrant cancer risk factors.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: M
authors.initials: M
authors.lastname: Berwick
authors.forename: I
authors.initials: I
authors.lastname: Orlow
authors.forename: S
authors.initials: S
authors.lastname: Mahabir
authors.forename: P
authors.initials: P
authors.lastname: Myskowski
authors.forename: D
authors.initials: D
authors.lastname: Coit
authors.forename: M S
authors.initials: MS
authors.lastname: Brady
authors.forename: P
authors.initials: P
authors.lastname: Roy
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: R
authors.initials: R
authors.lastname: Canchola
authors.forename: A
authors.initials: A
authors.lastname: Barz
authors.forename: A
authors.initials: A
authors.lastname: Halpern
authors.forename: J
authors.initials: J
authors.lastname: Bolognia
authors.forename: S
authors.initials: S
authors.lastname: Eng
authors.forename: A
authors.initials: A
authors.lastname: Elahi
authors.forename: C B
authors.initials: CB
authors.lastname: Begg
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics*; D009506:Nevus / Q000235:genetics; D009691:Nucleic Acid Denaturation / Q000235:genetics; D016017:Odds Ratio; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16