Clinicopathologic Features and Germline Sequence Variants in Young Patients (≤40 Years Old) With Pancreatic Ductal Adenocarcinoma

Ohmoto, Akihiro; Yachida, Shinichi; Kubo, Emi; Takai, Erina; Suzuki, Masami; Shimada, Kazuaki; Okusaka, Takuji; Morizane, Chigusa

doi:10.1097/mpa.0000000000000574

Cited by 20 publications

(11 citation statements)

References 38 publications

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“…The main differences between the two PDAC groups were seen in demographic data. EOPC patients in our population were more frequently males, in agreement with previous studies [ 5 – 7 , 12 , 13 , 36 , 37 ]. In addition, our EOPC patients were less frequently of white British background and more commonly Asian or from ‘any other white background’.…”

Section: Discussionsupporting

confidence: 93%

“…While the overall survival of EOPC was similar to older PDAC patients with no statistically significant difference, EOPC patients who underwent surgical resection had a longer median overall survival of 25 months compared to 13 months for the same PDAC subpopulation. A similar finding has been observed in previous studies, with the highest survival of 41.8 months for resected cases reported by Duffy et al [ 10 ] which has been attributed to young people having fewer comorbidities and being more suitable candidates for surgery and adjuvant chemotherapy [ 10 , 12 , 13 , 36 , 37 ]. Furthermore, He et al also showed that EOPC patients had fewer post-operative complications [ 12 ] and McWilliams et al, [ 14 ] attributed the better survival rate among young people to a multitude of factors, including race, sex, year of diagnosis, stage of disease, tumour location and treatment [ 14 ].…”

Section: Discussionsupporting

confidence: 89%

“…However, somewhat higher incidences were found by Piciucchi et al [ 7 ] in both young and older patients, where 8% and 6.3% of cases respectively had a family history of pancreatic cancer. A recent study by Ohmoto et al [ 37 ] suggests a lack of association between hereditary genetic factors and EOPC. The authors assessed the mutation status of 49 genes involved in hereditary syndromes in the germline of EOPC patients younger than 40 years, but did not find any variants [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recent study by Ohmoto et al [ 37 ] suggests a lack of association between hereditary genetic factors and EOPC. The authors assessed the mutation status of 49 genes involved in hereditary syndromes in the germline of EOPC patients younger than 40 years, but did not find any variants [ 37 ]. In contrast, James et al [ 17 ] reported an overall incidence of familial pancreatic cancer of 3%, with the percentage of patients ≤50 years of age being significantly higher than among the sporadic cancer patients (36% and 18.3%, respectively, p = 0.017).…”

Section: Discussionmentioning

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: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Ntala¹,

Debernardi²,

Feakins³

et al. 2018

BMC Gastroenterol

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“…When considered this signature in the clinical set, the predictive value was also robust in different subpopulation. Studies indicated early and late onset pancreatic cancer suffered different genomic alteration and clinicopathologic features (McWilliams et al, ; Ohmoto et al, ). Survival analysis in the TCGA cohort was not available to support this point, but our risk model was both feasible in patients with diagnostic age larger or <50 (Figure ).…”

Section: Discussionmentioning

confidence: 99%

Gene signature associated with neuro‐endocrine activity predicting prognosis of pancreatic carcinoma

Chen

Liu

et al. 2019

Molec Gen & Gen Med

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Background Genomic analysis is the promising tool to clear understanding of the tumorigenesis and guide molecular classification for pancreatic cancer. Our purpose was to develop a critical predictive model for prognosis in pancreatic carcinoma, based on the genomic data. Methods The online The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets were queried as training and validation cohorts for comprehensive bioinformatic analysis. We applied Lasso and multivariate Cox regression to shrink genes and construct predictive model. Results A four genes model (DNAH10: HR = 0.71, 95% CI = 0.57–0.88, HSBP1L1: HR = 1.51, 95% CI = 1.18–1.92, KIAA0513: HR = 0.69, 95% CI = 0.50–0.96, and MRPL3: HR = 3.73, 95% CI = 2.03–6.86), was proposed and validated. The C‐index was 0.73 (95% CI: 0.7–0.77). Patients in high‐risk and low‐risk group, stratified by model, suffered significantly different overall survival time (15.1 vs. 49.3 months, p < 0.0001 in TCGA; 423 vs. 618 days, p = 0.038 in ICGC). Taken clinical parameters into consideration, the risk‐score was independent marker in clinical subpopulation. To explore the molecular mechanisms, 579 differential expression genes (DEG) in two groups were identified by edgeR . Functional enrichment of DEG indicated neuro‐endocrine activity was the potential mechanism for the discrepant prognosis. Conclusion A specific four genes signature with the ability to predicted survival of pancreatic carcinoma was generated, which may indicate the connection between neuro‐endocrine activity and patients’ prognosis.

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Molecular characteristics of early‐onset pancreatic ductal adenocarcinoma

Debernardi,

Liszka,

Ntala

et al. 2024

Molecular Oncology

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The median age of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis is 71 years; however, around 10% present with early‐onset pancreatic cancer (EOPC), i.e., before age 50. The molecular mechanisms underlying such an early onset are unknown. We assessed the role of common PDAC drivers (KRAS, TP53, CDKN2A and SMAD4) and determined their mutational status and protein expression in 90 formalin‐fixed, paraffin‐embedded tissues, including multiple primary and matched metastases, from 37 EOPC patients. KRAS was mutated in 88% of patients; p53 was altered in 94%, and p16 and SMAD4 were lost in 86% and 71% of patients, respectively. Meta‐synthesis showed a higher rate of p53 alterations in EOPC than in late‐onset PDAC (94% vs. 69%, P = 0.0009) and significantly higher loss of SMAD4 (71% vs. 44%, P = 0.0025). The majority of EOPC patients accumulated aberrations in all four drivers; in addition, high tumour heterogeneity was observed across all tissues. The cumulative effect of an exceptionally high rate of alterations in all common PDAC driver genes combined with high tumour heterogeneity suggests an important mechanism underlying the early onset of PDAC.

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Clinicopathologic Features and Germline Sequence Variants in Young Patients (≤40 Years Old) With Pancreatic Ductal Adenocarcinoma

Abstract: The clinicopathologic features in young patients were generally similar to those in older patients. The rarity of family history of PDAC and the sequencing analysis for germline variants suggest that hereditary factors might have a weak, if any, relationship with early-onset PDAC.

Cited by 20 publications

References 38 publications

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

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

Gene signature associated with neuro‐endocrine activity predicting prognosis of pancreatic carcinoma

Molecular characteristics of early‐onset pancreatic ductal adenocarcinoma

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