title: Risk of subsequent cancers in renal cell carcinoma survivors with a family history.
abstract: BACKGROUND
  This study aimed at elucidating the effect of family history on the development of subsequent cancers in renal cell carcinoma (RCC) survivors and aimed at assessing whether the interactions between risks of subsequent cancers in RCC survivors and familial risk of subsequent cancer are additive or multiplicative interactions.
  
  
  METHODS
  A population-based cohort (Swedish Family-Cancer Database) of 14,267 RCC patients diagnosed in 1990-2010 was followed for cancer incidence. Standardised incidence ratios (SIRs) were calculated for subsequent cancers in RCC survivors and in RCC survivors with a family history of subsequent cancer. Familial risk of subsequent cancer was calculated for individuals with family history of specific cancer, compared to those without.
  
  
  RESULTS
  For subsequent hemangioblastoma (HB) in RCC survivors, drastically elevated risk was observed for the effect of family history of HB [SIR=777 (95% confidence interval (CI): 160-2270)] and of family history of RCC [378 (46-1367)]. Colorectal, lung, prostate and RCCs favoured additive interactions between risk of subsequent cancers in RCC survivors and familial risk, while endocrine glands, nervous system and urinary bladder cancers favoured multiplicative interactions.
  
  
  CONCLUSIONS
  Risks of subsequent HB in RCC survivors were tremendously modified by family history of RCC or HB, which may resemble characteristics of von Hippel-Lindau syndrome and show the power of present approach to detect heritable cancer clusters. Additive or multiplicative interactions found for colorectal, lung, prostate, endocrine glands, nervous system, urinary bladder and RCCs might raise awareness among clinicians and RCC survivors with a family history of seven cancers about elevated risks of subsequent those cancers.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69121, 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 69121, Germany.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fallah
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö SE-20502, Sweden; Stanford Prevention Research Center, Stanford University School of Medicine, CA 94305-5411, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69121, Germany; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69121, Germany; Center for Primary Health Care Research, Lund University, Malmö SE-20502, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000453:epidemiology*; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D012307:Risk Factors; D017741:Survivors; D013548:Sweden / Q000453:epidemiology
keywords: Aetiology; Family history; Renal cell carcinoma; Second primary malignancy; Survivors