Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk.

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk.

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07-1.15, P = 5.25 × 10-9 ). CDKN2B-AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases.

The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years' experience of association studies to understand the genetic architecture of pancreatic cancer.

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.

[Solid pseudopapillary neoplasms of the pancreas : Diagnostics, surgical treatment and postoperative outcome]. / Solid-pseudopapilläre Neoplasien des Pankreas : Diagnostik, chirurgische Therapie und postoperatives Outcome.

BACKGROUND: Malignant solid pseudopapillary neoplasms (SPN) are rare tumor entities of the pancreas. The prognosis for SPN is generally excellent, although some tumors have malignant potential and tend to metastasize or relapse. OBJECTIVE: The aim was to investigate whether there are histopathological or surgical risk factors that enable the biological potential of SPN to be estimated. PATIENTS AND METHODS: Data from patients with SPN treated in two large German pancreas centers from 2009 to 2018 were evaluated with respect to the occurrence of SPN, surgical management, histopathological tumor characteristics and the postoperative outcome. RESULTS: A total of 22 patients with SPN (17 women, 5 men) were operated on. The median age of the patients was 37 years (range 19-69 years). At the time of surgery 20 patients showed tumor growth limited to the pancreas. A female patient with recurrence of an externally resected SPN had lymph node involvement. Another female patient had a hepatic metastatic recurrence (Union Internationale contre Cancer (UICC) stage IV) of an externally resected SPN. Although all patients survived recurrence-free during the follow-up, this patient developed liver metastases again. The survival rate up to the end of the follow-up (median 43 months; range 1-132 months) of this study was 100%. CONCLUSION: There is a lack of knowledge of the possible parameters that can be used to predict the biological behavior of SPN. Apart from an increased likelihood of recurrence after resection of an SPN recurrence, no clear risk factors could be identified in the examined patient collective that could indicate an increased malignant potential and a possibly poorer outcome. Only a radical surgical resection with lymphadenectomy enables a reliable assessment of the tumor stage and the removal of possibly affected lymph nodes, which could be the cause of a recurrence if left intact.