Single Nucleotide Polymorphisms within the 8Q24 Region are Not Associated with the Risk of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Abstract

Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been reported to be associated with an increased risk of developing extra-pancreatic malignancies. A common genetic background has been hypothesised to be responsible for such an association. Human chromosomal region 8q24 has been associated with many types of cancer. The majority of these associations lie at approximately 128 Mb on chromosome 8. We conducted a study in order to examine the association between IPMN and single nucleotide polymorphisms (SNPs) from the 8q24 region, namely rs10505477, rs6983267, rs7014346, rs6993464, previously reported to influence general cancer susceptibility. Methods. The study was performed on 117 IPMN cases and 231 controls. Cases were enrolled at the Digestive Endoscopy Unit, Policlinico Agostino Gemelli from January, 2010 to June, 2011, with either a prevalent or incident IPMN diagnosis. Status of SNPs was determined using a StepOne Real-time PCR system (Applied Biosystems) and TaqMan SNP Genotyping Assay™ 40X. Unconditional multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for the association of selected SNPs and IPMNs. Results. Cases were more likely to report a 1st degree family history of cancer (p<0.001), as well as heavy smoking (p=0.001) and heavy drinking habits (p<0.001). No significant association was observed between IPMN and selected SNPs. The results were confirmed also when stratified according to any 1st-degree family history of cancer. Conclusion. Patients with IPMN do not have a higher prevalence of SNPs in the human chromosomal region 8q24 in respect to the control population. Abbreviations: CASC8: cancer susceptibility candidate 8; CRC: colorectal cancer; ENPP2: ectonucleotide pyrophosphatase/phosphodiesterase 2; EPM: extra-pancreatic malignancy; eQTLs: expression quantitative trait loci; IPMN: intraductal papillary mucinous neoplasm; MYC: myelocytomatosis viral oncogene homolog gene; NOV: nephroblastoma over-expressed gene; PCR: polymerase chain reaction; POU5F1P1: POU class 5 homeobox 1 pseudogene 1 gene; S-MRCP: magnetic resonance cholangiopancreatography with secretin stimulation; SNP: single nucleotide polymorphism; TCF4: transcription factor 4.