Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis

Epidemiologic evidence suggests a family history of pancreatic cancer (PC) is a risk factor for the disease, yet the magnitude of risk varies between studies. We performed a systematic review of studies that quantified familial risks of PC, and through a meta-analysis, obtained more precise estimates of familial risk. A MEDLINE search identified published studies that reported relative risks (RR) of PC associated with a family history of the disease. A random effects model was used to summarize study-specific RRs and 95% confidence intervals (CI). Sensitivity and sub-group analyzes were performed. Seven case-control and two cohort studies involving 6,568 PC cases were identified. There was no evidence of statistical heterogeneity between studies (I-2 = 0%; P = 0.483). Results from case-control (RR = 2.82; 95% CI: 1.99-3.66) and cohort (RR = 1.62; 95% CI: 1.28-1.97) studies showed a significant increase in PC risk associated with having an affected relative, with an overall summary RR = 1.80 (95% CI: 1.48-2.12). Similar RR were observed for early (RR = 2.69; 95% CI: 0.56-4.82) and later (RR = 3.41; 95% CI: 0.79-6.03) onset disease in the index case. Data was too sparse to generate an overall summary RR based on the number or type of affected relatives. Individuals with a family history of PC have nearly a two-fold increased risk for developing PC compared to those without such a history. Families with two or more PC cases may benefit from comprehensive risk assessment that involves collection of detailed family history information and data regarding various risk factors for PC, especially smoking history. Those at highest risk may be referred to screening programs and studies; these are important steps toward early detection and greater odds of surviving this disease.