Association between the polymorphism of three genes involved in the methylation and efflux of arsenic (As3MT, MRP1, and P‐gp) with lung cancer in a Mexican cohort

• Published in: Journal of applied toxicology Vol. 41; no. 9; pp. 1357 - 1366
• Main Authors: Recio‐Vega, Rogelio, Hernandez‐Gonzalez, Sandra, Michel‐Ramirez, Gladis, Olivas‐Calderón, Edgar, Lantz, R. Clark, Gandolfi, A. Jay, Amistadi, Mary Kay
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2021
• Subjects: Adult; Aged; Aged, 80 and over; Arsenic; Arsenic - analysis; Arsenic - metabolism; Arsenic - urine; As3MT; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics; Chronic exposure; Cohort Studies; Cross-Sectional Studies; DNA methylation; Drinking Water - analysis; Efflux; Environmental Exposure; Epidemiology; Female; Gene polymorphism; Genotype; Glycoproteins; Health risks; Humans; Intracellular levels; Lung cancer; Lung Neoplasms - chemically induced; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Male; Metabolism; Methylation; Methyltransferases - genetics; Mexico - epidemiology; Middle Aged; MRP1; Multidrug resistance; Multidrug Resistance-Associated Proteins - genetics; Organs; Polymorphism; Polymorphism, Genetic - genetics; Proteins; P‐gp; Risk analysis; Risk Factors; Surveys and Questionnaires; Young Adult; Mexico; lung cancer; As3MT; MRP1; polymorphism; P-gp; arsenic
• ISSN: 0260-437X; 1099-1263; 1099-1263
• DOI: 10.1002/jat.4127

Lung cancer is the most common neoplasm and the primary cause‐related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic methylation efficiency (As3MT) and the clearance of arsenic from cells by two members of the ATP‐binding cassette (ABC) transporter family (multidrug resistance protein 1 [MRP1] and P‐glycoprotein [P‐gp]) play an important role in processing of arsenic and decreasing its intracellular levels. This study aimed to evaluate the association between chronic exposure to arsenic with polymorphism of three proteins involved in arsenic metabolism and efflux of the metalloid in subjects with lung cancer. Polymorphism in As3MT, MRP1, and P‐gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1, and P‐gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1 polymorphism was associated with a twofold increase in the risk of lung cancer. Polymorphism in As3MT, MRP1 and P‐gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1 and P‐gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1polymorphism was associated with twofold increase in the risk of lung cancer.