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

Sari,Fatih  M.; Yanar,Hakan  T.; Ozhan,Gul

doi:10.3892/br.2014.383

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

Authors:
- Fatih M. Sari
- Hakan T. Yanar
- Gul Ozhan
View Affiliations

Affiliations: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey, Department of General Surgery, Faculty of Medicine, Istanbul University, Istanbul 34390, Turkey
Published online on: November 11, 2014 https://doi.org/10.3892/br.2014.383
Pages: 105-109

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Andersen V, Ostergaard M, Christensen J, et al: Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study. BMC Cancer. 9:4072009. View Article : Google Scholar
2	Chen P, Zhao L, Zou P, et al: The contribution of the ABCG2 C421A polymorphism to cancer susceptibility: A meta-analysis of the current literature. BMC Cancer. 12:3832012. View Article : Google Scholar : PubMed/NCBI
3	Dietrich CG, Vehr AK, Martin IV, et al: Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food-derived carcinogen. Int J Cancer. 129:546–552. 2011. View Article : Google Scholar
4	Guengerich FP: Metabolism of chemical carcinogens. Carcinogenesis. 21:345–351. 2000. View Article : Google Scholar : PubMed/NCBI
5	Shiloh Y: ATM and related protein kinases: Safeguarding genome integrity. Nat Rev Cancer. 3:155–168. 2003. View Article : Google Scholar : PubMed/NCBI
6	Dietrich CG, Geier A and Oude Elferink RP: ABC of oral bioavailability: Transporters as gatekeepers in the gut. Gut. 52:1788–1795. 2003. View Article : Google Scholar : PubMed/NCBI
7	Klein I, Sarkadi B and Varadi A: An inventory of the human ABC proteins. Biochim Biophys Acta. 1461:237–262. 1999. View Article : Google Scholar : PubMed/NCBI
8	Velamakanni S, Wei SL, Janvilisri T, et al: ABCG transporters: Structure, substrate specificities and physiological roles: A brief overview. J Bioenerg Biomembr. 39:465–471. 2007. View Article : Google Scholar : PubMed/NCBI
9	Allikmets R, Schriml LM, Hutchinson A, et al: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 58:5337–5339. 1998.PubMed/NCBI
10	Doyle LA, Yang W, Abruzzo LV, et al: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA. 95:15665–15670. 1998. View Article : Google Scholar : PubMed/NCBI
11	Isshiki M, Umezawa K and Tamura H: Coffee induces breast cancer resistance protein expression in Caco-2 cells. Biol Pharm Bull. 34:1624–1627. 2011. View Article : Google Scholar : PubMed/NCBI
12	Lockhart AC, Tirona RG and Kim RB: Pharmacogenetics of ATP-binding cassette transporters in cancer and chemotherapy. Mol Cancer Ther. 2:685–698. 2003. View Article : Google Scholar : PubMed/NCBI
13	Staud F and Pavek P: Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol. 37:720–725. 2005. View Article : Google Scholar
14	Campa D, Pardini B, Naccarati A, et al: A gene-wide investigation on polymorphisms in the ABCG2/BRCP transporter and susceptibility to colorectal cancer. Mutat Res. 645:56–60. 2008. View Article : Google Scholar : PubMed/NCBI
15	Ebert B, Seidel A and Lampen A: Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists. Carcinogenesis. 26:1754–1763. 2005. View Article : Google Scholar
16	Gupta N, Martin PM, Miyauchi S, et al: Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. Biochem Biophys Res Commun. 343:571–577. 2006. View Article : Google Scholar
17	Jonker JW, Buitelaar M, Wagenaar E, et al: The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci USA. 99:15649–15654. 2002. View Article : Google Scholar : PubMed/NCBI
18	Pavek P, Merino G, Wagenaar E, et al: Human breast cancer resistance protein: Interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther. 312:144–152. 2005. View Article : Google Scholar
19	Compton CC and Greene FL: The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin. 54:295–308. 2004. View Article : Google Scholar : PubMed/NCBI
20	Krishnamurthy P and Schuetz JD: Role of ABCG2/BCRP in biology and medicine. Annu Rev Pharmacol Toxicol. 46:381–410. 2006. View Article : Google Scholar
21	Maliepaard M, Scheffer GL, Faneyte IF, et al: Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 61:3458–3464. 2001.PubMed/NCBI
22	Mao Q and Unadkat JD: Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J. 7:E118–E133. 2005. View Article : Google Scholar : PubMed/NCBI
23	Muller P, Asher N, Heled M, et al: Polymorphisms in transporter and phase II metabolism genes as potential modifiers of the predisposition to and treatment outcome of de novo acute myeloid leukemia in Israeli ethnic groups. Leuk Res. 32:919–929. 2008. View Article : Google Scholar
24	Sarkadi B, Ozvegy-Laczka C, Nemet K, et al: ABCG2 - a transporter for all seasons. FEBS Lett. 567:116–120. 2004. View Article : Google Scholar : PubMed/NCBI
25	Schinkel AH and Jonker JW: Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: An overview. Adv Drug Deliv Rev. 55:3–29. 2003. View Article : Google Scholar : PubMed/NCBI
26	Dai D, Zeldin DC, Blaisdell JA, et al: Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics. 11:597–607. 2001. View Article : Google Scholar : PubMed/NCBI
27	Eisenblatter T and Galla HJ: A new multidrug resistance protein at the blood-brain barrier. Biochem Biophys Res Commun. 293:1273–1278. 2002. View Article : Google Scholar : PubMed/NCBI
28	Jonker JW, Smit JW, Brinkhuis RF, et al: Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst. 92:1651–1656. 2000. View Article : Google Scholar : PubMed/NCBI
29	Jonker JW, Merino G, Musters S, et al: The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med. 11:127–129. 2005. View Article : Google Scholar : PubMed/NCBI
30	Korenaga Y, Naito K, Okayama N, et al: Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma. Int J Cancer. 117:431–434. 2005. View Article : Google Scholar : PubMed/NCBI
31	Kruijtzer CM, Beijnen JH, Rosing H, et al: Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol. 20:2943–2950. 2002. View Article : Google Scholar : PubMed/NCBI
32	Haimeur A, Conseil G, Deeley RG, et al: The MRP-related and BCRP/ABCG2 multidrug resistance proteins: Biology, substrate specificity and regulation. Curr Drug Metab. 5:21–53. 2004. View Article : Google Scholar : PubMed/NCBI
33	Zamber CP, Lamba JK, Yasuda K, et al: Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics. 13:19–28. 2003. View Article : Google Scholar : PubMed/NCBI
34	Kondo C, Suzuki H, Itoda M, et al: Functional analysis of SNPs variants of BCRP/ABCG2. Pharm Res. 21:1895–1903. 2004. View Article : Google Scholar
35	Mizuarai S, Aozasa N and Kotani H: Single nucleotide polymorphisms result in impaired membrane localization and reduced ATPase activity in multidrug transporter ABCG2. Int J Cancer. 109:238–246. 2004. View Article : Google Scholar
36	Liu HG, Pan YF, You J, et al: Expression of ABCG2 and its significance in colorectal cancer. Asian Pac J Cancer Prev. 11:845–848. 2010.PubMed/NCBI
37	Hu LL, Wang XX, Chen X, et al: BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma. Carcinogenesis. 28:1740–1744. 2007. View Article : Google Scholar : PubMed/NCBI
38	Pollex EK, Anger G, Hutson J, et al: Breast cancer resistance protein (BCRP)-mediated glyburide transport: Effect of the C421A/Q141K BCRP single-nucleotide polymorphism. Drug Met Dispos. 38:740–744. 2010. View Article : Google Scholar : PubMed/NCBI
39	de Jong FA, Marsh S, Mathijssen RH, et al: ABCG2 pharmacogenetics: Ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin Cancer Res. 10:5889–5894. 2004.PubMed/NCBI
40	Imai Y, Nakane M, Kage K, et al: C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Mol Cancer Ther. 1:611–616. 2002.PubMed/NCBI
41	Kobayashi D, Ieiri I, Hirota T, et al: Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metab Dispos. 33:94–101. 2005. View Article : Google Scholar : PubMed/NCBI
42	Itoda M, Saito Y, Shirao K, et al: Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotecan. Drug Metab Pharmacokinet. 18:212–217. 2003. View Article : Google Scholar
43	Backstrom G, Taipalensuu J, Melhus H, et al: Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population. Eur J Pharm Sci. 18:359–364. 2003. View Article : Google Scholar : PubMed/NCBI
44	Noguchi K, Katayama K, Mitsuhashi J, et al: Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 61:26–33. 2009. View Article : Google Scholar