Familial risk of cancer by site and histopathology

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Abstract
Familial risks for histopathology-specific cancers have not been determined. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 1 million tumors to calculate standardized incidence ratios (SIRs) for familial cancers of specific histology and morphology among 0- to 66-year-old offspring. We used histology codes for both offspring and parents, but because of the limited number of cases, the morphology-specific classification could be used only for offspring by all site-specific cancers in parents, resulting in inflated risk estimates. A number of novel findings emerged in the histopathology-specific analysis of familial risks, in addition to some known associations. Overall, specific histology showed an SIR of 2.07 for all cancers compared to an SIR of 2.00 for any histology. However, the small effect was due to breast and prostate cancers, which showed a negligible effect of specific histology. Familial risks of over 4.0 were found for serous papillary cystadenocarcinoma of the ovary, papillary thyroid cancer and low-grade astrocytoma. Familial risks of over 3.0 were found for signet-ring gastric cancer, various forms of ovarian cancer and squamous cell skin cancer. Also noteworthy were familial risks of hepatocellular carcinoma (2.48), pancreatic adenocarcinoma (1.92), large cell carcinoma and adenocarcinoma of the lung (2.29 and 2.18, respectively) and clear cell carcinoma of the kidney (2.73). Many of the findings were novel and could be revealed only by applying codes for specific histopathology. These data call for a closer description of familial aggregations and probing for the underlying genetic mechanisms.