Early onset pancreatic cancer: Risk factors, presentation and outcome

Piciucchi, Matteo; Capurso, Gabriele; Valente, Roberto; Larghi, Alberto; Archibugi, Lívia; Signoretti, Marianna; Stigliano, Serena; Zerboni, Giulia; Barucca, Viola; Torre, Marco La; Cavallini, Marco; Costamagna, Guido; Marchetti, Paolo; Ziparo, Vincenzo; Fave, Gianfranco Delle

doi:10.1016/j.pan.2015.01.013

Cited by 66 publications

(86 citation statements)

References 26 publications

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“…mucinous cystic neoplasms) which are not included in the current WHO classification of pancreatic ductal adenocarcinoma, our report is based on the most recent PDAC classification and staging. We have used 50 years as the cut-off age for EOPC patients, which, although arbitrary, has been used previously [ 4 – 7 ]. A detailed summary of comparisons between different EOPC studies is shown in Table 5 .…”

Section: Discussionmentioning

confidence: 99%

“…It is the fourth leading cause of cancer death with a 7% five-year survival rate in the United States [ 1 ], and is predicted to be the second cause of cancer-related death by 2030 [ 2 ]. The mean age of PDAC patients at presentation is 71 years [ 3 ]; however, 5–10% of these patients are diagnosed with this malignancy at a young age, when they are less than 50 years old [ 4 – 7 ]. This important subgroup of PDAC patients, often referred to as early onset pancreatic cancer (EOPC), has been poorly studied, and the cause of such an early presentation of the disease remains unknown [ 6 , 8 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Demographic, clinical, and pathological features of early onset pancreatic cancer patients

Ntala¹,

Debernardi²,

Feakins³

et al. 2018

BMC Gastroenterol

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BackgroundEarly onset pancreatic cancer (EOPC), i.e. pancreatic ductal adenocarcinoma (PDAC) occurring in patients below 50 years of age, is rare and there is limited information regarding risk factors, molecular basis and outcome. This study aimed to determine the demographic and clinicopathological features and survival figures for EOPC.MethodsA retrospective analysis of patients treated at the Royal London Hospital for PDAC between September 2004 and September 2015 was performed. Data on demographics, risk factors, presentation, pathological features, treatment and survival outcome were compared in EOPC and older PDAC patients.ResultsOf 369 PDAC cases identified, 35 (9.5%) were EOPC. Compared to older patients, EOPC patients were more frequently male (71% vs 54%, p = 0.043) and less commonly of British origin (37% vs 70%, p = 0.002). There was no significant difference regarding the prevalence of any of the risk factors known to be associated with older PDAC patients. Fewer EOPC patients presented with resectable disease (23% vs 44%, p = 0.015) and more received adjuvant chemo/radiotherapy (60% vs 46%, p = 0.008). The overall median survival and stage specific survival did not differ significantly between the two groups, although a longer survival for localized disease was seen in EOPC patients (25 months (12.9–37, 95%CI) vs 13 months (10.5–15.5 95%CI) for older PDAC patients).ConclusionsThe EOPC patients had different demographics and were more likely than their older PDAC counterparts to be male. Typically they presented with more advanced disease, received more aggressive treatment, and had on overall similar survival outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Demographic, clinical, and pathological features of early onset pancreatic cancer patients

Ntala¹,

Debernardi²,

Feakins³

et al. 2018

BMC Gastroenterol

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“…[4][5][6][7][8][9][10][11][12][13][14][15] The median age of onset of pancreatic cancer is 71 years and around 20% of subjects develop it before 60 years of age, defined as early onset pancreatic cancer (EOPC). [16][17][18][19] Only around 3% of cases are diagnosed before 45 years of age (very early onset pancreatic cancer, VEOPC). 17 EOPC and VEOPC share the majority of epidemiologic risk factors with non-EOPC (NEOPC), with smoking being the strongest for both ages of onset.…”

Section: Introductionmentioning

confidence: 99%

“…17 EOPC and VEOPC share the majority of epidemiologic risk factors with non-EOPC (NEOPC), with smoking being the strongest for both ages of onset. 16,17 Not much is known on the genetic background of EOPC, however in a recent report Ben-Aharon and colleagues comparing the somatic mutation landscape of NEOPC and EOPC, found several differences in the pathways involved. 20 In addition, only one study has been performed to identify germline single nucleotide polymorphisms (SNPs) specifically associated with EOPC.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide association study identifies an early onset pancreatic cancer risk locus

Campa

Gentiluomo

Obazee

et al. 2020

Intl Journal of Cancer

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Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome‐wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I‐II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10−4). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta‐analysis supported the association (P = 1.15 × 10−4). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

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“…However, 5-10% of all pancreatic cancer cases present with Early Onset Pancreatic Cancer (EOPC) defined as the occurrence of a cancer before age 50(8). While it has been suggested that this group of patients may have an underlying genetic predisposition to pancreatic cancer(9), not all studies report an increased risk of pancreatic cancer among the relatives of EOPC patients (7,10). …”

Section: Introductionmentioning

confidence: 99%

Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study

Childs

Chaffee

Gallinger

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e. BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch-repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before age 50), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iCOGS array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR=1.36, 95%CI (1.13-1.63), p=9.29×10-4; 7p13, rs17688601: OR =0.76, 95%CI (0.63-0.93), p=6.59×10-3). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (p<5×10-5) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility.

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Early onset pancreatic cancer: Risk factors, presentation and outcome

Cited by 66 publications

References 26 publications

Demographic, clinical, and pathological features of early onset pancreatic cancer patients

Demographic, clinical, and pathological features of early onset pancreatic cancer patients

Genome‐wide association study identifies an early onset pancreatic cancer risk locus

Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study

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