title: Multiple primary (even in situ) melanomas in a patient pose significant risk to family members.
abstract: BACKGROUND
  We aimed at assessing familial risk of melanoma by considering a detailed family history of multiple primary (invasive/in situ) melanomas (MPM), stratified by histology and location.
  
  
  METHODS
  Among 65,429 melanoma patients diagnosed in 1958-2010 in the Swedish Family-Cancer Database, there were 4248 patients with familial melanoma. A detailed family history of MPM was investigated by number of melanomas in one first-degree relative (FDR) and in ⩾2 FDRs. Familial melanoma risk was assessed by standardised incidence ratios (SIRs) comparing those with family history of melanoma to those without. Combining invasive/in situ melanoma was due to essentially identical familial risks.
  
  
  RESULTS
  For one affected FDR, familial risk increased from SIR=2.2 (95% confidence interval (CI)=2.2-2.3) for single melanoma to 16.3 (9.5-26.1) for ⩾5 melanomas, while for ⩾2 affected FDRs, the risk increased from 5.5 (4.8-6.2) for single melanoma to 23.9 (13.6-38.8) for ⩾2 melanomas. Significantly higher familial risks for superficial spreading melanoma (SSM) [2.5 (2.3-2.6)] than lentigo maligna melanoma (LMM) [1.8 (1.6-2.1)], and for multiple parts [5.3 (3.1-8.4)] and trunk [2.6 (2.5-2.8)] than head/neck [2.0 (1.8-2.2)] were observed. Only at head/neck, significantly higher risk for SSM [2.4 (1.9-3.0)] than LMM [1.6 (1.4-1.8)] was noted.
  
  
  CONCLUSIONS
  We found, for the first time, that familial risks were similar for two/three melanomas in one FDR or for a single melanoma in ⩾2 FDRs and, higher familial risks for SSM than LMM occurred only at head/neck. This study provides new evidence for genetic counselling in melanoma, suggesting the need for considering not only the number of affected family members but also the diagnosis of MPM (even in situ) in relatives.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. Electronic address: t.chen@dkfz.de.
authors.forename: Tianhui
authors.initials: T
authors.lastname: Chen
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Elham
authors.initials: E
authors.lastname: Kharazmi
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Ji
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University School of Medicine, CA, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fallah
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016208:Databases, Factual / Q000706:statistics & numerical data; D005190:Family; D005192:Family Health; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology* / Q000235:genetics; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics; D013548:Sweden / Q000453:epidemiology
keywords: Age at diagnosis; Familial risk; Family history; First-degree relatives; Histology; Melanoma; Multiple primary melanomas