Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study

BMC Cancer

Research Article

Deborah Postil¹  Claire Thalamas²  Rosine Guimbaud³  Eric Terrebonne⁴  Nicole Tubiana-Mathieu⁵  Sabrina Falkowski⁵  Denis Smith⁶  Antoine Pariente⁷  Koukeb Rouguieg-Malki⁸  Pierre Marquet⁸  Jean-Baptiste Woillard⁸  Nicolas Picard⁹ 

[1] Clinical Investigation Centre, CHU Limoges, Limoges, France;Clinical Investigation Centre, University Hospital Toulouse, Toulouse, France;Digestive Oncology Department, University Hospital Toulouse, Toulouse, France;Hepato-gastro-enterology Department, University Hospital Bordeaux, Bordeaux, France;Oncology Department, CHU Limoges, Limoges, France;Oncology Department, University Hospital Bordeaux, Bordeaux, France;Pharmaco-epidemiology unit, University Hospital Bordeaux, Bordeaux, France;UMR-1248, Inserm, CHU Limoges, Univ. Limoges, Limoges, France;UMR-1248, Inserm, CHU Limoges, Univ. Limoges, Limoges, France;Service de Pharmacologie, Toxicologie et Pharmacovigilance, CHU Limoges, Bâtiment CBRS, 2 avenue Martin-Luther King, F-87042, Limoges, France;

关键词: Colorectal cancer;    Pharmacogenetics;    UGT;    Efflux transporters;    OATP;   

DOI  :  10.1186/s12885-017-3728-0

 received in 2016-10-31, accepted in 2017-10-30,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAssociations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC.MethodsThree hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6–9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and “environmental” risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with “environmental” risk factors.ResultsNo significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29–8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10–3.39], p = 0.0257) in the “never alcohol consumption subgroup” (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70–10.9], p < 0.0001), living or working in rural or mix area (OR = 2.50[1.48–4.23], p = 0.0006 and OR = 2.99[1.63–5.48], p = 0.004, respectively) and tobacco exposure >30 years (3.37[1.63–6.96], p = 0.0010).ConclusionsVariant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup.Trial registrationRegistered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008–0144.

【 授权许可】

CC BY   
© The Author(s). 2017