Importance of Age of Onset in Pancreatic Cancer Kindreds

Abstract

BackgroundYoung-onset cancer is a hallmark of many familial cancer syndromes, yet the implications of young-onset disease in predicting risk of pancreatic cancer among familial pancreatic cancer (FPC) kindred members remain unclear.MethodsTo understand the relationship between age at onset of pancreatic cancer and risk of pancreatic cancer in kindred members, we compared the observed incidence of pancreatic cancer in 9040 individuals from 1718 kindreds enrolled in the National Familial Pancreas Tumor Registry with that observed in the general US population (Surveillance, Epidemiology, and End Results). Standardized incidence ratios (SIRs) were calculated for data stratified by familial vs sporadic cancer kindred membership, number of affected relatives, youngest age of onset among relatives, and smoking status. Competing risk survival analyses were performed to examine the risk of pancreatic cancer and risk of death from other causes according to youngest age of onset of pancreatic cancer in the family and the number of affected relatives.ResultsRisk of pancreatic cancer was elevated in both FPC kindred members (SIR = 6.79, 95% confidence interval [CI] = 4.54 to 9.75, P < .001) and sporadic pancreatic cancer (SPC) kindred members (SIR = 2.41, 95% CI = 1.04 to 4.74, P = .04) compared with the general population. The presence of a young-onset patient (<50 years) in the family did not alter the risk for SPC kindred members (SIR = 2.74, 95% CI = 0.05 to 15.30, P = .59) compared with those without a young-onset case in the kindred (SIR = 2.36, 95% CI = 0.95 to 4.88, P = .06). However, risk was higher among members of FPC kindreds with a young-onset case in the kindred (SIR = 9.31, 95% CI = 3.42 to 20.28, P < .001) than those without a young-onset case in the kindred (SIR = 6.34, 95% CI = 4.02 to 9.51, P < .001). Competing risk survival analyses indicated that the lifetime risk of pancreatic cancer in FPC kindreds increased with decreasing age of onset in the kindred (hazard ratio = 1.55, 95% CI = 1.19 to 2.03 per year). However, youngest age of onset for pancreatic cancer in the kindred did not affect the risk among SPC kindred members.ConclusionsIndividuals with a family history of pancreatic cancer are at a statistically significantly increased risk of developing pancreatic cancer. Having a member of the family with a young-onset pancreatic cancer confers an added risk in FPC kindreds.

Risk Factors in Pancreatic Cancer

“…The risk of pancreatic cancer was similar in familial PC kindred compared to sporadic pancreatic cancer kindred members. Analysing more than 9000 subjects, the presence of a young-onset pancreatic cancer patient, under 50 years old did not influence the risk of having pancreatic cancer inside familial PC kindred, but it added risk compared to sporadic pancreatic cancer (Brune et al, 2010). Smoking is a strong risk factor in familial pancreatic cancer kindred, particularly in males and people younger than 50 years of age, as it increases the risk of pancreatic cancer by 2 to 3.7 times over the inherited predisposition and lowers the age of onset by 10 years (Rulyak et al, 2003).…”

Pancreatic Cancer Screening: Attempts and Possibilities

“…Risk factors for pancreatic cancer are relatively nonspecific, and include age, obesity, diabetes, smoking, and genetic chronic pancreatitis. In a smoking population with a family history of pancreatic cancer, we recommend screening to start earlier as they have greater risk than non-smokers [26]; despite there is being no consensus recommendation.…”

Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer

“…This risk has been estimated to be 2.3 to 4.5-fold greater in individuals with one FDR with pancreatic cancer, 6.4-fold greater in individuals with two FDRs with the disease and 32 to 57-fold greater in individuals with three or more FDRs affected [29][30][31][32] . Similarly to other familial tumors, the median age of presentation in patients with FPC is up to 20 years earlier than in patients with sporadic cancer (49 years vs 61 years) [33][34][35] with an ''anticipation phenomenon'' in the affected kindred and a trend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next [35,36] . Currently, the genetic etiology of most cases of FPC remains undetermined but complex segregation analysis of these patients has led to the discovery of various candidate pancreatic cancer susceptibility genes such as BRCA2 (6%-17% of cases) [37,38] , partner and localizer of BRCA2 (PALB2) (1%-4% of cases) [39,40] and palladin, even if mutations of the latter have been identified in normal controls as well [41][42][43] .…”