UGT1A1 Gene Polymorphism Contributes as a Risk Factor for Lung Cancer: A Pilot Study with Patients from the Amazon.

Esdras E B Pereira,Antônio A C Modesto,Marianne R Fernandes,Bruno M Fernandes,João F Guerreiro,Luciana P C Leitão,Rommel M R Burbano,Sidney E B Dos Santos,Paulo P Assumpção,Roberta B Andrade,Ney P C Dos Santos

doi:10.3390/genes13030493

Abstract

Lung cancer is one of the most frequent neoplasms in the world. Because it is a complex disease, its formation occurs in several stages, stemming from interactions between environmental risk factors, such as smoking, and individual genetic susceptibility. Our objective was to investigate associations between a UGT1A1 gene polymorphism (rs8175347) and lung cancer risk in an Amazonian population. This is a pilot study, case-controlled study, which included 276 individuals with cancer and without cancer. The samples were analyzed for polymorphisms of the UGT1A1 gene (rs8175347) and genotyped in PCR, followed by fragment analysis in which we applied a previously developed set of informative ancestral markers. We used logistic regression to identify differences in allelic and genotypic frequencies between individuals. Individuals with the TA7 allele have an increased chance of developing lung adenocarcinoma (p = 0.035; OR: 2.57), as well as those with related genotypes of reduced or low enzymatic activity: TA6/7, TA5/7, and TA7/7 (p = 0.048; OR: 8.41). Individuals with homozygous TA7/7 have an increased chance of developing squamous cell carcinoma of the lung (p = 0.015; OR: 4.08). Polymorphism in the UGT1A1 gene (rs8175347) may contribute as a risk factor for adenocarcinoma and lung squamous cell carcinoma in the population of the Amazon region.

Highlights

Lung neoplasms are among the most prevalent types of cancer in the world population, representing 11.4% of all registered cancers, and are responsible for 18% of cancer deaths [1]
Lung cancer can be divided into two categories, small cell lung cancer (SCLC), responsible for 15–20% of cases; and non-small cell lung cancer (NSCLC), which represents 80–85% of cases [3,4]
The well-known risk factor for the development of lung cancer is smoking, given the presence of substances contained in tobacco associated with carcinogenesis [5]

Summary

Introduction

Lung neoplasms are among the most prevalent types of cancer in the world population, representing 11.4% of all registered cancers, and are responsible for 18% of cancer deaths [1] This frequency varies between countries, depending on their demographic characteristics, smoking rate, and level of economic development [2]. Studies have shown that about half of new cases are in people who have never smoked, or have stopped smoking for many years [6]. This shows that pulmonary carcinogenesis is a complex and gradual process, with complex interactions between environmental risk factors and individual genetic susceptibility [7]

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