Investigation of the functional single-nucleotide polymorphisms in the BCRP transporter and susceptibility to colorectal cancer.

Breast cancer resistance protein (BCRP) protects tissues by actively transporting xenobiotics and their metabolites out of the cells. BCRP is expressed in the apical membrane of normal intestinal and colonic epithelium. The BCRP substrates include a number of structurally unrelated compounds, such as drugs, pesticides, carcinogens and endogenous compounds. Although the functional and common BCRP alleles, 34G>A and 421C>A, are shown to vary by ethnicity, their potential mechanism has not been adequately described with regards to affecting the susceptibility to colorectal cancer. The present study aimed to evaluate the effects of the BCRP variants on the susceptibility to colorectal cancer and to predict the individual responses to xenobiotics transferred by BCRP. BCRP 421C>A was significantly associated with the colorectal cancer risk (odds ratio, 16.12; P=0.005). These findings are the first results of BCRP allele distributions in the Turkish population and provide an understanding of the correlation between therapeutic approaches and etiology of colorectal cancer.

Influence of the functional polymorphisms in the organic anion transporting polypeptide 1B1 in the susceptibility to colorectal cancer.

Colorectal cancer is an important cause of death throughout the world, and its etiology involves the interaction of genetic and environmental factors. Transporter proteins are important in protecting organs from xenobiotics or toxins. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays role in hepatic uptake and clearance of albumin-bound amphipathic organic compounds, including endogen substances, drugs, or xenobiotics. The SLCO1B1 gene expressing OATP1B1 is highly polymorphic. Up to now, SLCO1BI variants were the focus of several investigations on drug pharmacokinetics and cancer susceptibility. However, no information has been available on association between SLCO1B1 and colorectal cancer risk. Therefore, the study aims to investigate the relationship between colorectal cancer and the functional common variants of SLCO1B1 (388 A>G, -11187 G>A, 521 T>C) and to estimate the prevalence of these variants in the Turkish population. To that end, the distributions of the variants were determined in 100 patients with colorectal cancer and 150 healthy volunteers. SLCO1B1 521 T>C was statistically significantly associated with colorectal cancer risk (odds ratio [OR]=2.66; 95% confidence interval [CI]=1.31-5.41; p=0.0057). In haplotype-based analysis, SLCO1B1 haplotype G(388)-T(11187)-T(521) might be associated with the development of colorectal cancer (OR=4.26; 95% CI=1.62-11.16; p=0.002). We believe that the findings may be beneficial to the development of efficacious preventive strategies and therapies for colorectal cancer.

Associations between the functional polymorphisms in the ABCB1 transporter gene and colorectal cancer risk: a case-control study in Turkish population.

Colorectal cancer is among the most common cancer types in the world and its etiology involves the interaction of genetic and environmental factors. ABCB1 is highly expressed in the apical surface of colonic epithelial cells and acts as an efflux pump by transporting toxic endogenous substances, drugs and xenobiotics out of cells. ABCB1 polymorphisms may either change its protein expression or alter its function. Several studies have reported a possible association between ABCB1 variants and colorectal cancer, but no consistent conclusion has been arrived at. Therefore, we aimed to investigate the relationship between colorectal cancer and the functional common variants of ABCB1 (1236C > T; 2677G > T/A; 3435C > T). The distributions of the variants were determined in 103 patients with colorectal cancer and 150 healthy volunteers using polymerase chain reaction-restriction fragment length polymorphism methods. ABCB1 1236C > T was statistically significantly associated with colorectal cancer risk (OR, odd ratio = 1.91; 95% CI, confidence interval = 1.09-3.35; p = 0.034). In haplotype-based analysis, the proportion of individuals with the ABCB1 haplotype C1236-G2677-T3435 was significantly more common in patients than in controls (OR = 11.96; 95% CI = 2.59-55.32; p = 0.0004). We believe that the findings may be beneficial to the development of efficacious preventive strategies and therapies for colorectal cancer.