Family history of cancer, Ashkenazi Jewish ancestry, and pancreatic cancer risk

Tsuyoshi Hamada,Peter Kraft,Matthew B Yurgelun,Edward L Giovannucci,Ana Babic,Natalia Khalaf,Meir J Stampfer,Chen Yuan,Brian M Wolpin,Kimberly Perez,Charles S Fuchs,Marios Giannakis,Shuji Ogino,Kimmie Ng,Douglas A Rubinson,Vicente Morales-Oyarvide,Jonathan A Nowak

doi:10.1038/s41416-019-0426-5

Abstract

BackgroundIndividuals with a family history of cancer may be at increased risk of pancreatic cancer. Ashkenazi Jewish (AJ) individuals carry increased risk for pancreatic cancer and other cancer types.MethodsWe examined the association between family history of cancer, AJ heritage, and incident pancreatic cancer in 49 410 male participants of the prospective Health Professionals Follow-up Study. Hazard ratios (HRs) were estimated using multivariable-adjusted Cox proportional hazards models.ResultsDuring 1.1 million person-years (1986–2016), 452 participants developed pancreatic cancer. Increased risk of pancreatic cancer was observed in individuals with a family history of pancreatic (HR, 2.79; 95% confidence interval [CI], 1.28–6.07) or breast cancer (HR, 1.40; 95% CI, 1.01–1.94). There was a trend towards higher risk of pancreatic cancer in relation to a family history of colorectal cancer (HR, 1.21; 95% CI, 0.95–1.55) or AJ heritage (HR, 1.29; 95% CI, 0.94–1.77). The risk was highly elevated among AJ men with a family history of breast or colorectal cancer (HR, 2.61 [95% CI, 1.41–4.82] and 1.92 [95% CI, 1.05–3.49], respectively).ConclusionFamily history of pancreatic cancer was associated with increased risk of this malignancy. Family history of breast or colorectal cancer was associated with the increased risk among AJ men.

Highlights

Individuals with a family history of cancer may be at increased risk of pancreatic cancer
In addition to environmental and lifestyle factors shared by family members, studies have identified genes that contribute to familial clustering of pancreatic cancer, including ATM, BRCA1, BRCA2, CDKN2A, and PALB2, as well as PRSS1 and SPINK1 for hereditary pancreatitis.[12,13,14,15,16,17,18]
Within a large U.S cohort with 30 years of follow-up, we prospectively examined the association of family history of cancer with risk of incident pancreatic cancer

Summary

Introduction

Individuals with a family history of cancer may be at increased risk of pancreatic cancer. History of breast or colorectal cancer was associated with the increased risk among AJ men. Pancreatic cancer is the third leading cause of cancer-related mortality in the United States (U.S.) with an overall 5-year survival rate of

Methods

Results

Conclusion