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

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.

Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders

“…The UGT1A1 gene is implicated in the development of several cancer subtypes, including colon, breast, and prostate cancer. The UGT1A1 enzyme is involved in the metabolism of various drugs, including anticancer agents [ 37 ]. The UGT1A1 gene is significantly polymorphic, and several SNPs impact UGT1A1 enzyme activity.…”

Gilbert’s syndrome as a model for studying the effects of bilirubin

“…Наконец, четвертый клинический сценарий связан с потенциальным протективным влиянием гипербилирубинемии на течение ряда заболевания. Многочисленными эпидемиологическими исследованиями, метаанализами и экспериментальными работами продемонстрировано снижение риска сердечно-сосудистых заболеваний, сахарного диабета 2 типа и их осложнений, а также ряда онкологических заболеваний, однако для некоторых вариантов онкозаболеваний, особенно на примере малых когорт обследуемых, протективного эффекта СЖ показано не было [31][32][33][34][35][36][37][38][39][40][41][42]. Более того, на сегодняшний день в связи с расширением представлений о физиологических и патофизиологических эффектах билирубина и его гормональной активности ряд исследователей предлагают выделять понятие «гипобилирубинемии», определять референсные значения низких уровней билирубина и обсуждать потенциальную негативную роль низкой концентрации билирубина [31,38,43].…”

“…Лица с гомозиготным генотипом TA7/7 имеют повышенный риск развития плоскоклеточного рака легкого (p = 0,015; ОШ = 4,08). Авторы делают заключение, что для когорты пациентов полиморфизм гена UGT1A1 (rs8175347) может быть фактором риска развития аденокарциномы и плоскоклеточного рака легких у населения [40]. Результаты этого исследования еще раз свидетельствуют о гено-фенотипическом разнообразии СЖ в зависимости от расовой принадлежности когорты обследуемых и размеров изучаемой выборки.…”

Genetic Polymorphisms of ACE1 Rs4646994 Associated with Lung Cancer in Patients with Pulmonary Nodules: A Case–Control Study

“…Risk factors for increasing the likelihood of lung nodule carcinogenesis include the following: current or previous smoking, older, personal cancer history, family history of lung cancer, emphysema, exposure to asbestos or radon and EGFR mutation [ 5 , 6 , 7 , 8 ]. This suggests that the development of pulmonary nodules into lung cancer is a complex and gradual process [ 9 ]. In recent years, several studies have reported the correlation between single nucleotide polymorphisms (SNPs) of genes related to metabolism, DNA damage repair, cell cycle regulation and lung diseases [ 9 , 10 , 11 , 12 ].…”

“…This suggests that the development of pulmonary nodules into lung cancer is a complex and gradual process [ 9 ]. In recent years, several studies have reported the correlation between single nucleotide polymorphisms (SNPs) of genes related to metabolism, DNA damage repair, cell cycle regulation and lung diseases [ 9 , 10 , 11 , 12 ]. The treatment of patients with pulmonary nodules should be guided by the probability of malignant nodules, the safety of detection, and other additional tests [ 13 ].…”