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巴西人群胰腺癌的易感性基因座。

Susceptibility loci for pancreatic cancer in the Brazilian population.

机构信息

Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, PR, Brazil.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

BMC Med Genomics. 2021 Apr 20;14(1):111. doi: 10.1186/s12920-021-00956-5.

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.

摘要

背景

胰腺导管腺癌(PA)是一种侵袭性很强的癌症,预后最差。通常,诊断较晚且对常规治疗有抗性。环境和遗传因素促成了其病因,例如烟草和酒精的使用、慢性胰腺炎、糖尿病和肥胖。已知胰腺癌细胞存在体细胞突变,GWAS 的 SNP 图谱可以在不同的人群背景下获得该疾病的新的遗传风险因素。在这里,我们描述了一个用于巴西胰腺癌症的 SNP 面板,以及临床和流行病学数据。

方法

对 78 名胰腺导管腺癌患者和 256 名非胰腺癌症患者进行了 25 个 SNP 的实时 PCR 基因分型。使用条件逻辑回归方法评估等位基因、共显性和显性遗传模型对 PA 风险的主要影响。

结果

9 个 SNP 与胰腺导管腺癌风险呈显著相关,其中 5 个次要等位基因具有保护作用,而 4 个与风险因素相关。在流行病学和临床数据中,吸烟、糖尿病和胰腺炎病史与胰腺导管腺癌风险显著相关。使用研究中的 SNPs 计算的多基因风险评分与 PA 风险具有很强的关联。

结论

我们首次在巴西人群中评估了一些与 PA 相关的 SNP,这一结果可用于家族性胰腺癌、吸烟者、饮酒者和糖尿病患者等高危人群的遗传筛查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2748/8056496/763827777e27/12920_2021_956_Fig1_HTML.jpg

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