Risk of Pancreatic Cancer in the Long-Term Prospective Follow-Up of Familial Pancreatic Cancer Kindreds

Abstract

Background A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (>1 relative) are imprecise due to small samples sizes or potentially impacted by biases inherent in retrospective data. Objective Determine the age-specific pancreatic cancer risk as a function of family history using prospective data. Methods We compared pancreatic cancer incidence (n = 167) in 21,141 individuals from 4,433 families enrolled in the National Familial Pancreatic Cancer Registry to that expected based upon Surveillance Epidemiology and End Results (SEER) data and estimated the cumulative probability of pancreatic cancer using competing risk regression. Results Familial pancreatic kindred members (FPC, kindreds with pancreatic cancer in two first-degree relatives or a pathogenic variant) had a standardized incidence ratio (SIR) of 4.86 (95% CI 4.01-5.90), and NFPTR sporadic kindreds members (SPC, kindreds not meeting familial criteria) had an SIR of 2.55 (95% CI 1.95-3.34). Risk in FPC kindreds increased with an increasing number of first-degree relatives with pancreatic cancer, with SIR of 3.46 (95% CI 2.52-4.76), 5.44 (95% CI 4.07-7.26), 10.78 (95% CI 6.87-16.89) for 1, 2 and 3 or more first-degree-relatives with pancreatic cancer, respectively. Risk was also higher among individuals with a family history of young-onset(<50) pancreatic cancer. Conclusion Pancreatic cancer risk is strongly dependent on family history, including both the degree-of-relationship(s) and age-of-onset of pancreatic cancer in relatives. These risk estimates will help inform the design of early detection studies and the risk/benefit analysis of screening trials.

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

“…Given the intensity of screening paradigms, there is a natural tension in identifying an optimal cohort meeting a threshold whereby the benefits outweigh the risks. A family history of pancreatic cancer is a significant predictor of disease risk, with some series suggesting a six-fold or higher risk compared with the general population 179 , with an increasing number of family members affected with an elevated risk 180 . The risk is also increased for kindred in whom disease onset was particularly young (that is less than 50 years of age) 180 .…”

“…A family history of pancreatic cancer is a significant predictor of disease risk, with some series suggesting a six-fold or higher risk compared with the general population 179 , with an increasing number of family members affected with an elevated risk 180 . The risk is also increased for kindred in whom disease onset was particularly young (that is less than 50 years of age) 180 . Taken together, the International Cancer of the Pancreas Screening Consortium recommends that screening programmes are implemented for individuals with an estimated lifetime risk of 5 per cent or greater 181 .…”

Developing and validating a pancreatic cancer risk model for the general population using multi-institutional electronic health records from a federated network

“…We calculated SIR by dividing the observed PDAC cases in the high-risk group by the expected number of PDAC cases of that group. To calculate the expected number of cases, we used the SEER database [1], matched with age, sex, race, and calendar year for each individual in the high-risk group, as done by Porter et al [24].…”

“…Since we used all the PDAC cases in the TriNetX database, but sampled a subset of control patients, we accounted for this imbalance to estimate the PPV and SIR that would be obtained if we had evaluated the model on the full TriNetX population.We calculated SIR by dividing the observed PDAC cases in the high-risk group by the expected number of PDAC cases of that group. To calculate the expected number of cases, we used the SEER database[1], matched with age, sex, race, and calendar year for each individual in the high-risk group, as done by Porter et al[24].…”

Orderly Aggregated Catalytic Hairpin Assembly for Synchronous Ultrasensitive Detecting and High-Efficiency Co-Localization Imaging of Dual-miRNAs in Living Cells

“…MicroRNAs (miRNAs) are a kind of single-stranded noncoding RNA composed of 18–24 nucleotides, which participate in the regulation of many physiological processes by controlling mRNA translation. – A great deal of research evidence identify that the imbalance of specific miRNA expression is closely related to the occurrence of cancer or other pathological conditions, so some specific miRNAs have been identified as biomarkers for cancer diagnosis, therapy, and prognosis. – Pancreatic ductal adenocarcinoma (PDAC) is considered to be one of the mortal neoplasms with the worst prognosis, which is difficult to diagnose at an early stage. – Previous studies have demonstrated that miRNA-196a is significantly upregulated but miRNA-217 is markedly downregulated in PDAC, while miRNA-217 was highly expressed and miRNA-196a was low expressed in normal pancreas . Therefore, exploring simultaneous ultrasensitive detection and precise colocalization imaging of miR-217 and miR-196a in living cells holds immense importance in the early diagnosis of pancreatic cancer and ensure detection specificity.…”