Susceptibility loci for pancreatic cancer in the Brazilian population

Mateus Nóbrega Aoki,Roger Chammas,Miyuki Uno,Anelis Maria Marin,Federico Canzian,Francielle Boçon De Araújo Munhoz,Jaqueline Carvalho De Oliveira,Angelika Stein

doi:10.1186/s12920-021-00956-5

Abstract

BackgroundPancreatic 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.Methods78 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.Results9 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.ConclusionWe 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.

Highlights

Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses
The present study evaluated 25 Single nucleotide polymorphism (SNP), previously associated with PA risk in genome-wide association studies (GWAS) to investigate the influence of these loci in the Brazilian population, including 78 patients with pancreatic adenocarcinoma and 256 controls without cancer history
The first SNP is located at the first intron of NR5A2, with Minor allele frequency (MAF) in global population of 25%, and we observed a similar value of 27% in our control group, while in PA patients this value was 18%, returning an Odds ratio (OR) that represents a protective effect of this allele for PA

Summary

Introduction

Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. 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. A major cause for the poor prognosis is the late diagnosis and the resistance to conventional treatment [3] and, differently from other tumor types, mortality rates for PA are not improving [4, 5]. Environmental and genetic factors contribute to the etiology of PA, as the consumption of tobacco is an important risk factor [8, 9]. Other risk factors include the excessive consumption of alcohol, chronic pancreatitis, diabetes, obesity and dietary-endocrine factors [10, 11].

Methods

Results

Discussion

Conclusion