title: Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype.
abstract: BACKGROUND
  As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC).
  
  
  METHODS
  Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R.
  
  
  RESULTS
  A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35).
  
  
  CONCLUSIONS
  Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC.
authors.affiliation: Yale School of Public Health, New Haven, CT 06520, United States.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Berlin
authors.affiliation: Yale School of Public Health, New Haven, CT 06520, United States; Yale Cancer Center, New Haven, CT 06520, United States.
authors.forename: Brenda
authors.initials: B
authors.lastname: Cartmel
authors.affiliation: Yale Cancer Center, New Haven, CT 06520, United States; Yale University School of Medicine, New Haven, CT 06520, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Leffell
authors.affiliation: Yale Cancer Center, New Haven, CT 06520, United States; Yale University School of Medicine, New Haven, CT 06520, United States.
authors.forename: Allen E
authors.initials: AE
authors.lastname: Bale
authors.affiliation: Yale School of Public Health, New Haven, CT 06520, United States; Yale Cancer Center, New Haven, CT 06520, United States.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Mayne
authors.affiliation: Yale School of Public Health, New Haven, CT 06520, United States; Yale Cancer Center, New Haven, CT 06520, United States. Electronic address: leah.ferrucci@yale.edu.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D044102:Receptor, Melanocortin, Type 1
keywords: Basal cell carcinoma; Epidemiology; Family history; Skin cancer