title: The population impact of familial cancer, a major cause of cancer.
abstract: The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant cancers among spouses. Almost all cancers showed a significant familial risk. The highest PAFs were found for the common cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96% for the invasive and in situ cancers in the FDRs and SDRs. The cancers between spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among spouses was higher than the familial risk. Our study shows that the overall familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Frank
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fallah
authors.forename: Jianguang
authors.initials: J
authors.lastname: Ji
authors.forename: Jan
authors.initials: J
authors.lastname: Sundquist
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology*; D002278:Carcinoma in Situ / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D004938:Esophageal Neoplasms / Q000453:epidemiology; D005190:Family; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D011471:Prostatic Neoplasms / Q000453:epidemiology*; D012306:Risk; D012307:Risk Factors
keywords: Sweden; familial risk; population attributable fraction; spouse risk; standardized incidence ratio