Susceptibility loci for pancreatic cancer in the Brazilian population

Abstract

Background Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. Usually, the diagnosis is late and resistant to conventional treatment. Environmental and genetic factors contribute to the etiology, such as tobacco and alcohol consumption, chronic pancreatitis, diabetes and obesity. Somatic mutation in pancreatic cancer cells are known and SNP profile by GWAS could access novel genetic risk factors for this disease in different population context. Here we describe a SNP panel for Brazilian pancreatic cancer, together with clinical and epidemiological data. Methods 78 pancreatic adenocarcinoma and 256 non-pancreatic cancer subjects had 25 SNPs genotyped by real-time PCR. Unconditional logistic regression methods were used to assess the main effects on PA risk, using allelic, co-dominant and dominant inheritance models. Results 9 SNPs were nominally associated with pancreatic adenocarcinoma risk, with 5 of the minor alleles conferring protective effect while 4 related as risk factor. In epidemiological and clinical data, tobacco smoking, diabetes and pancreatitis history were significantly related to pancreatic adenocarcinoma risk. Polygenic risk scores computed using the SNPs in the study showed strong associations with PA risk. Conclusion We could assess for the first time some SNPs related with PA in Brazilian populations, a result that could be used for genetic screening in risk population such as familial pancreatic cancer, smokers, alcohol users and diabetes patients.

Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer

“…More recently, germline genotyping for patients has been moving towards more assertive cohorts related to ethnicity, age, and the molecular and clinical characteristics of tumors [ 72 , 73 , 74 , 75 ]. The composition of the cohorts chosen, however, may bias the molecular epidemiology findings: A recent report using 2039 patients and 32,592 controls in the Japanese population identified three genome-wide significant loci (13q12.2, 13q22.1, and 16p12.3), among which 16p12.3 has not been reported in the Western population [ 76 ].…”