Dataset Information

Association between ABCB1, ABCG2 carrier protein and COX-2 enzyme gene polymorphisms and breast cancer risk in a Turkish population.

ABSTRACT: Aim:Breast cancer is the most common cancer and the second leading cause of cancer-related deaths among women. Several genetic and environmental factors are known to be involved in breast cancer pathogenesis, but the exact etiology of this disease is complicated and not completely understood. We aimed to investigate whether the gene polymorphisms of ABCB1 and ABCG2 carrier proteins and COX-2 enzyme affect breast cancer risk. Method:ABCG2 C421A (rs2231142), ABCB1 C3435T (rs1045642), COX-2 T8473C (rs5275) and COX-2 G306C (rs5277) were genotyped 104 breast cancer patients and 90 healthy controls using a real-time PCR for breast cancer susceptibility. Results:Patients carrying ABCG2 C421A, the CC genotype, had a higher risk of disease compared with patients carrying any A allele (OR = 3.06; 95% CI = 1.49-6.25, p = 0.0019). The other variants showed no association with breast cancer (p > 0.05). Comparing the pathological parameters with the variants, only, the frequency of C allele of ABCB1 C3435T was significantly lower in the estrogen receptor-? (ER?) (OR = 2.25; 95% CI: 0.75-6.76; p = 0.041) and progesterone receptor (PgR) (OR = 3.67; 95% CI: 1.34-10.03; p = 0.008) positive breast cancer patients. Conclusion:ABCB1 C3435T and ABCG2 C421A might represent a potential risk factor for breast cancer for Turkish women.

SUBMITTER: Zeliha KP

PROVIDER: S-EPMC7000306 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Association between ABCB1, ABCG2 carrier protein and COX-2 enzyme gene polymorphisms and breast cancer risk in a Turkish population.

Zeliha Kara Pala KP Dilek Ozturk O Ezgi Oztas O Halil Kara K Cihan Uras U Gul Ozhan O

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 20191207 2

<h4>Aim</h4>Breast cancer is the most common cancer and the second leading cause of cancer-related deaths among women. Several genetic and environmental factors are known to be involved in breast cancer pathogenesis, but the exact etiology of this disease is complicated and not completely understood. We aimed to investigate whether the gene polymorphisms of ABCB1 and ABCG2 carrier proteins and COX-2 enzyme affect breast cancer risk.<h4>Method</h4><i>ABCG2 C421A</i> (rs2231142), <i>ABCB1 C3435T</ ...[more]

PMID: 32042261

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Project description:Introduction:Genetic polymorphisms of drug transporters influence drug transporter activity and alter pharmacokinetic profiles of the drugs. Organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) are important transporters encoded by solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene and ATP-binding cassette subfamily G member 2 (ABCG2) gene, respectively. Polymorphisms in these genes are associated with increased plasma statins concentrations, statin-induced myopathy and poor response to allopurinol treatment. Purpose:We explored allele and genotype frequencies of SLCO1B1 and ABCG2 genes including their predicted phenotypes in 53 Thai participants. Of these, 17 had chronic kidney disease and were on statins. Materials and Methods:Genotyping analysis for SLCO1B1 c.521T>C (rs4149056), c.388A>G (rs2306283), g.-11187G>A (rs4149015), and ABCG2 c.421C>A (rs2231142) was done by using TaqMan® Real time PCR. All were tested for Hardy-Weinberg Equilibrium. Results:Most of the participants (80%) had normal function haplotypes SLCO1B1 (*1A and *1B) while decreased (*5, *15, and *17) and unknown (*21) function haplotypes were less observed. Four phenotypes of SLCO1B1 were observed: 69.81% had normal function (*1A/*1A,*1A/*1B, and *1B/*1B), 13.21% had intermediate function (*1A/*17, *1B/*15 and *1B/*17), 9.43% had indeterminate function (*1A/*21 and *1B/*21) and 7.55% had low function (*5/*15, *15/*15, and *15/*17). ABCG2 c.421A allele frequency was 25%. The frequency of ABCG2 c.421CA and AA phenotypes were 37.7% and 5.7%, respectively. The allele and genotype frequencies observed are consistent with reports in Asians. However, there were differences in major allele distributions between Asians and Caucasians for SLCO1B1 c.388A>G; SLCO1B1 c.388G were highly found in Asians, but c.388A were more observed in Caucasians. Conclusion:This study showed that in the Thai population, there were 4 SNPs of SLCO1B1 and ABCG2 genes. This finding may be clinically applied to minimize inter-individual variability of drugs such as statins and allopurinol. Further study with a larger sample size is needed to assess the drug profiles and responses to treatment.

Project description:Tyrosine kinase inhibitors (TKIs) have radically changed the outcome of chronic myeloid leukemia (CML) patients in the last 20 years. Moreover, the advent of second generation TKIs, namely nilotinib and dasatinib, have largely increased the number of CML patients achieving deep and sustained molecular responses. However, the possible mechanisms capable of influencing the maintenance of the long-term molecular response are not yet fully known and understood. In this light, polymorphisms in MDR-ABC transporters may influence the efficacy and safety of TKIs. In this study, we examined seven single nucleotide polymorphisms (SNPs) in four ABC transporter genes: ABCC1 rs212090 (5463T>A), ABCC2 rs3740066 (3972C>T), ABCC2 rs4148386 G>A, ABCC2 rs1885301 (1549G>A), ABCG2 rs2231137 (34G>A), ABCG2 rs2231142 G>C, ABCB1 rs1045642 (3435C>T), to determine their effect on the achievement and/or loss of molecular response in 90 CML patients treated with nilotinib. We found that ABCC2 rs3740066 CC and CT as well as the ABCB1 rs1045642 TT genotypes correlated with a higher probability to achieve MR3 in a shorter time (p=0.02, p=0.004, and p=0.01), whereas ABCG2 rs2231137 GG was associated with lower probability of MR3 achievement (p=0.005). Moreover, ABCC2 rs3740066 CC genotype, the ABCB1 rs1045642 CC and TT genotypes were positively correlated with MR4 achievement (p=0.02, p=0.007, and p=0.003). We then generated a predictive model incorporating the information of four genotypes, to evaluate the combined effect of the SNPs. The combination of SNPs present in the model affected the probability and the time to molecular response. This model had a high prognostic significance for both MR3 and MR4 (p=0.005 and p=0.008, respectively). Finally, we found ABCG2 rs2231142 GG genotype to be associated with a decrease risk of MR3 loss. In conclusion, MDR-transporters SNPs may significantly affect the achievement and loss of molecular response in CML patients treated with nilotinib.

Dataset Information

Association between ABCB1, ABCG2 carrier protein and COX-2 enzyme gene polymorphisms and breast cancer risk in a Turkish population.

Publications

Association between ABCB1, ABCG2 carrier protein and COX-2 enzyme gene polymorphisms and breast cancer risk in a Turkish population.

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