Polymorphisms of xenobiotic-metabolizing and transporter genes and the risk of gastric and colorectal cancer in an admixed population of Brazil.

Abstract

Introduction Colorectal (CRC) and Gastric (GC) cancers are responsible for considerable morbidity and mortality worldwide. In the North region of Brazil, these neoplasms are among the three most incident and aggressive types of cancer, constituting a severe problem of public health. Single Nucleotide Polymorphisms (SNPs) of xenobiotic metabolism and transporter genes may play a role in individual response to exposure to some of the compounds implicated in the cancer susceptibility. However, few studies have demonstrated the role of polymorphisms of xenobiotic metabolism and transporter genes in the susceptibility to CRC or GC in admixed populations. In this context, the study of variation in the activation and detoxification processes of xenobiotics may help to clarify the development of either GC or CRC in substructured populations, providing new insights about predictive diagnostic criteria in oncological investigations. MethodsWe performed an association study using 31 SNPs in 15 xenobiotic metabolism and transporter genes. The study was carried out in 121 CRC and 95 GC cases and 140 control individuals from Belém, a city which comprises a population with high levels of miscegenation, located in the Brazilian Amazon. Samples were genotyped using the QuantStudio™12K Flex Real-Time PCR System. Due to the high level of genetic admixture in the studied population, we applied a panel of 61 Ancestry Informative Marker standardized by our research group in an earlier study. Statistical analyses were performed in SPSS v.20.0 and Structure v.2.3.4ResultsThe results revealed a significant association between the increased CRC or GC risk and polymorphisms of ABCG2 (rs2231142) and DPYD genes (rs17116806, rs1801159). ConclusionsOur data suggest that polymorphisms in xenobiotic-metabolizing and transporter genes may be relevant to the susceptibility to both CRC and GC.