title: Surveillance of second-degree relatives from melanoma families with a CDKN2A germline mutation.
abstract: BACKGROUND
  Lifetime melanoma risk of mutation carriers from families with a germline mutation in the CDKN2A gene is estimated to be 67%. The necessity to include family members in a melanoma surveillance program is widely endorsed, but there is no consensus on which family members should be invited.
  
  
  METHODS
  In a retrospective follow-up study, we investigated the yield of surveillance of first- and second-degree relatives of melanoma and pancreatic cancer patients from 21 families with the "p16-Leiden" CDKN2A mutation. Melanoma incidence rates were compared with the general population.
  
  
  RESULTS
  Three-hundred and fifty-four first-degree relatives and 391 second-degree relatives were included. Forty-five first-degree relatives and 11 second-degree relatives were diagnosed with melanoma. Most (72%) of second-degree relatives diagnosed with melanoma had become a first-degree relative before diagnosis, due to the occurrence of a melanoma in a parent or sibling. Overall, melanoma incidence rate was 2.1 per 1,000 person years [95% confidence interval (CI), 1.2-3.8] in family members still being second-degree relatives at diagnosis, compared with 9.9 per 1,000 person years (95% CI, 7.4-13.3) in first-degree relatives. The standardized morbidity ratio for melanoma of second-degree relatives compared with the general population was 12.9 (95% CI, 7.2-23.4).
  
  
  CONCLUSIONS
  Second-degree relatives from families with the p16-Leiden mutation in CDKN2A have a considerably increased melanoma risk compared with the general population.
  
  
  CONCLUSIONS
  This study provides justification for the surveillance of second-degree relatives from families with a CDKN2A germline mutation.
authors.affiliation: Authors' Affiliations: Department of Dermatology, Medical Statistics and Clinical Epidemiology, Clinical Genetics, Leiden University Medical Center, Leiden; Medical Affairs, Agendia, Amsterdam; Department of Pathology, VU University Medical Center, Amsterdam; The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden; and Department of Gastroenterology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jasper I
authors.initials: JI
authors.lastname: van der Rhee
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Boonk
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Cannegieter
authors.forename: Linda E
authors.initials: LE
authors.lastname: Flinterman
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
authors.forename: Femke A
authors.initials: FA
authors.lastname: de Snoo
authors.forename: Wolter J
authors.initials: WJ
authors.lastname: Mooi
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Kukutsch
authors.forename: Wilma
authors.initials: W
authors.lastname: Bergman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005192:Family Health; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma