Skip to main content

Advertisement

SpringerLink
Log in

Cytochrome P450 1B1 polymorphisms and risk of renal cell carcinoma in men

  • Research Article
  • Published:
Tumor Biology

Abstract

The cytochrome P450 1B1 (CYP1B1) enzyme activates xenobiotics to reactive forms as well as convert estradiol to 4-hydroxy-estradiol that has been shown to play a role in the carcinogenesis process of the kidney in male but not female animals. Prior reports show polymorphic variants of CYP1B1 to alter catalytic activity, and thus, we hypothesize that polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell in men. The genetic distributions of five CYP1B1 polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism in 480 normal healthy subjects and 403 sporadic renal cell carcinoma cases. All subjects were Caucasian men. The sites evaluated were codons 48 (C → G, Arg → Gly, rs10012), 119 (G → T, Ala → Ser, rs1056827), 432 (C → G, Leu → Val, rs1056836), 449 (C → T, Asp, rs1056837), and 453 (A → G, Asn → Ser, rs1800440). A trend was demonstrated for the 432 Val/Val (χ2, P = 0.06) and 449 T/T (χ2, P = 0.1) genotypes to play a protective role against renal cancer. Odds ratio (95 % confidence interval) for Val/Val compared to Leu/Leu at codon 432 was 0.65 (0.44–0.95) and T/T compared to C/C at codon 449 was 0.67 (0.45–0.99). Codons 432 and 449 were observed to be linked (D = 0.24), and haplotype involving 432 Val and 449 T was significantly reduced in cancer cases (P = 0.04). No association was found, however, when analyzing polymorphic sites with clinical stage of cancer. These results demonstrate polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of renal cell carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, et al. The epidemiology of renal cell carcinoma. Eur Urol. 2011;60(4):615–21.

    Article  PubMed  Google Scholar 

  2. Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 2010;7(5):245–57.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012;62(2):118–28.

    Article  PubMed  Google Scholar 

  4. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    Article  PubMed  Google Scholar 

  5. Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005;353(23):2477–90.

    Article  CAS  PubMed  Google Scholar 

  6. Newbold RR, Bullock BC, McLachlan JA. Uterine adenocarcinoma in mice following developmental treatment with estrogens: a model for hormonal carcinogenesis. Cancer Res. 1990;50(23):7677–81.

    CAS  PubMed  Google Scholar 

  7. Walker BE, Kurth LA. Pituitary tumors in mice exposed prenatally to diethylstilbestrol. Cancer Res. 1993;53(7):1546–9.

    CAS  PubMed  Google Scholar 

  8. Bosland MC, Ford H, Horton L. Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague–Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17 beta or diethylstilbestrol. Carcinogenesis. 1995;16(6):1311–7.

    Article  CAS  PubMed  Google Scholar 

  9. Li JJ, Li SA, Klicka JK, Parsons JA, Lam LK. Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney. Cancer Res. 1983;43(11):5200–4.

    CAS  PubMed  Google Scholar 

  10. Li JJ, Li SA. Estrogen carcinogenesis in Syrian hamster tissues: role of metabolism. Fed Proc. 1987;46(5):1858–63.

    CAS  PubMed  Google Scholar 

  11. Liehr JG, Sirbasku DA, Jurka E, Randerath K, Randerath E. Inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by tamoxifen without decrease in DNA adduct levels. Cancer Res. 1988;48(4):779–83.

    CAS  PubMed  Google Scholar 

  12. Kirkman H, Bacon RL. Malignant renal tumors in male hamsters (Cricetus auratus) treated with estrogen. Cancer Res. 1950;10(2):122–4.

    CAS  PubMed  Google Scholar 

  13. Liehr JG, Fang WF, Sirbasku DA, Ari-Ulubelen A. Carcinogenicity of catechol estrogens in Syrian hamsters. J Steroid Biochem. 1986;24(1):353–6.

    Article  CAS  PubMed  Google Scholar 

  14. Hayes CL, Spink DC, Spink BC, Cao JQ, Walker NJ, Sutter TR. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci U S A. 1996;93(18):9776–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Sutter TR, Tang YM, Hayes CL, Wo YY, Jabs EW, Li X, et al. Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2. J Biol Chem. 1994;269(18):13092–9.

    CAS  PubMed  Google Scholar 

  16. Muskhelishvili L, Thompson PA, Kusewitt DF, Wang C, Kadlubar FF. In situ hybridization and immunohistochemical analysis of cytochrome P450 1B1 expression in human normal tissues. J Histochem Cytochem. 2001;49(2):229–36.

    Article  CAS  PubMed  Google Scholar 

  17. Tsuchiya Y, Nakajima M, Yokoi T. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 2005;227(2):115–24.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang Y, Gaikwad NW, Olson K, Zahid M, Cavalieri EL, Rogan EG. Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007;56(7):887–94.

    Article  CAS  PubMed  Google Scholar 

  19. Han X, Liehr JG. DNA single-strand breaks in kidneys of Syrian hamsters treated with steroidal estrogens: hormone-induced free radical damage preceding renal malignancy. Carcinogenesis. 1994;15(5):997–1000.

    Article  CAS  PubMed  Google Scholar 

  20. Chakravarti D, Mailander PC, Li KM, Higginbotham S, Zhang HL, Gross ML, et al. Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene. Oncogene. 2001;20(55):7945–53.

    Article  CAS  PubMed  Google Scholar 

  21. Ragavan N, Hewitt R, Cooper LJ, Ashton KM, Hindley AC, Nicholson CM, et al. CYP1B1 expression in prostate is higher in the peripheral than in the transition zone. Cancer Lett. 2004;215(1):69–78.

    Article  CAS  PubMed  Google Scholar 

  22. Gajjar K, Martin-Hirsch PL, Martin FL. CYP1B1 and hormone-induced cancer. Cancer Lett. 2012;324(1):13–30.

    Article  CAS  PubMed  Google Scholar 

  23. Shimada T, Fujii-Kuriyama Y. Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1. Cancer Sci. 2004;95(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  24. Williams JA, Martin FL, Muir GH, Hewer A, Grover PL, Phillips DH. Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue. Carcinogenesis. 2000;21(9):1683–9.

    Article  CAS  PubMed  Google Scholar 

  25. John K, Divi RL, Keshava C, Orozco CC, Schockley ME, Richardson DL, et al. CYP1A1 and CYP1B1 gene expression and DNA adduct formation in normal human mammary epithelial cells exposed to benzo[a]pyrene in the absence or presence of chlorophyllin. Cancer Lett. 2010;292(2):254–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Martin FL, Patel II, Sozeri O, Singh PB, Ragavan N, Nicholson CM, et al. Constitutive expression of bioactivating enzymes in normal human prostate suggests a capability to activate pro-carcinogens to DNA-damaging metabolites. Prostate. 2010;70(14):1586–99.

    Article  CAS  PubMed  Google Scholar 

  27. Kitagawa K, Kunugita N, Kitagawa M, Kawamoto T. CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity. J Biol Chem. 2001;276(21):17830–5.

    Article  CAS  PubMed  Google Scholar 

  28. Legrand M, Stucker I, Marez D, Sabbagh N, Lo-Guidice JM, Broly F. Influence of a mutation reducing the catalytic activity of the cytochrome P450 CYP2D6 on lung cancer susceptibility. Carcinogenesis. 1996;17(10):2267–9.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang ZY, Fasco MJ, Huang L, Guengerich FP, Kaminsky LS. Characterization of purified human recombinant cytochrome P4501A1-Ile462 and -Val462: assessment of a role for the rare allele in carcinogenesis. Cancer Res. 1996;56(17):3926–33.

    CAS  PubMed  Google Scholar 

  30. Hanna IH, Dawling S, Roodi N, Guengerich FP, Parl FF. Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. Cancer Res. 2000;60(13):3440–4.

    CAS  PubMed  Google Scholar 

  31. Shen LX, Basilion JP, Stanton Jr VP. Single-nucleotide polymorphisms can cause different structural folds of mRNA. Proc Natl Acad Sci U S A. 1999;96(14):7871–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet. 2003;12(3):205–16.

    Article  CAS  PubMed  Google Scholar 

  33. Faa V, Coiana A, Incani F, Costantino L, Cao A, Rosatelli MC. A synonymous mutation in the CFTR gene causes aberrant splicing in an italian patient affected by a mild form of cystic fibrosis. J Mol Diagn. 2010;12(3):380–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Salinas-Sanchez AS, Donate-Moreno MJ, Lopez-Garrido MP, Gimenez-Bachs JM, Escribano J. Role of CYP1B1 gene polymorphisms in bladder cancer susceptibility. J Urol. 2012;187(2):700–6.

    Article  CAS  PubMed  Google Scholar 

  35. Zheng W, Xie DW, Jin F, Cheng JR, Dai Q, Wen WQ, et al. Genetic polymorphism of cytochrome P450-1B1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2000;9(2):147–50.

    CAS  PubMed  Google Scholar 

  36. Okobia MN, Bunker CH, Garte SJ, Zmuda JM, Ezeome ER, Anyanwu SN, et al. Cytochrome P450 1B1 Val432Leu polymorphism and breast cancer risk in Nigerian women: a case control study. Infect Agent Cancer. 2009;4 Suppl 1:S12.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Jiao H, Liu C, Guo W, Peng L, Chen Y, Martin FL. Association of CYP1B1 polymorphisms with breast cancer: a case-control study in the Han Population in Ningxia Hui Autonomous Region, P. R. China. Biomark Insights. 2010;5:21–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Shah PP, Singh AP, Singh M, Mathur N, Mishra BN, Pant MC, et al. Association of functionally important polymorphisms in cytochrome P4501B1 with lung cancer. Mutat Res. 2008;643(1–2):4–10.

    Article  CAS  PubMed  Google Scholar 

  39. Holt SK, Rossing MA, Malone KE, Schwartz SM, Weiss NS, Chen C. Ovarian cancer risk and polymorphisms involved in estrogen catabolism. Cancer Epidemiol Biomarkers Prev. 2007;16(3):481–9.

    Article  CAS  PubMed  Google Scholar 

  40. Beuten J, Gelfond JA, Byrne JJ, Balic I, Crandall AC, Johnson-Pais TL, et al. CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians. Carcinogenesis. 2008;29(9):1751–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Zhang H, Li L, Xu Y. CYP1B1 polymorphisms and susceptibility to prostate cancer: a meta-analysis. PLoS One. 2013;8(7):e68634.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Sasaki M, Tanaka Y, Okino ST, Nomoto M, Yonezawa S, Nakagawa M, et al. Polymorphisms of the CYP1B1 gene as risk factors for human renal cell cancer. Clin Cancer Res. 2004;10(6):2015–9.

    Article  CAS  PubMed  Google Scholar 

  43. Salinas-Sanchez AS, Sanchez-Sanchez F, Donate-Moreno MJ, Rubio-del-Campo A, Serrano-Oviedo L, Gimenez-Bachs JM, et al. GSTT1, GSTM1, and CYP1B1 gene polymorphisms and susceptibility to sporadic renal cell cancer. Urol Oncol. 2012;30(6):864–70.

    Article  CAS  PubMed  Google Scholar 

  44. Tang YM, Wo YY, Stewart J, Hawkins AL, Griffin CA, Sutter TR, et al. Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem. 1996;271(45):28324–30.

    Article  CAS  PubMed  Google Scholar 

  45. Paracchini V, Raimondi S, Gram IT, Kang D, Kocabas NA, Kristensen VN, et al. Meta- and pooled analyses of the cytochrome P-450 1B1 Val432Leu polymorphism and breast cancer: a HuGE-GSEC review. Am J Epidemiol. 2007;165(2):115–25.

    Article  PubMed  Google Scholar 

  46. Helmig S, Hadzaad B, Dohrel J, Schneider J. Influence of the Cyp1B1 L432V gene polymorphism and exposure to tobacco smoke on Cyp1B1 mRNA expression in human leukocytes. Drug Metab Dispos. 2009;37(7):1490–5.

    Article  CAS  PubMed  Google Scholar 

  47. Nock NL, Tang D, Rundle A, Neslund-Dudas C, Savera AT, Bock CH, et al. Associations between smoking, polymorphisms in polycyclic aromatic hydrocarbon (PAH) metabolism and conjugation genes and PAH-DNA adducts in prostate tumors differ by race. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1236–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Hunt R, Sauna ZE, Ambudkar SV, Gottesman MM, Kimchi-Sarfaty C. Silent (synonymous) SNPs: should we care about them? Methods Mol Biol. 2009;578:23–39.

    Article  CAS  PubMed  Google Scholar 

  49. Bruun GH, Doktor TK, Andresen BS. A synonymous polymorphic variation in ACADM exon 11 affects splicing efficiency and may affect fatty acid oxidation. Mol Genet Metab. 2013;110(1–2):122–8.

    Article  CAS  PubMed  Google Scholar 

  50. Tsao D, Shabalina SA, Gauthier J, Dokholyan NV, Diatchenko L. Disruptive mRNA folding increases translational efficiency of catechol-O-methyltransferase variant. Nucleic Acids Res. 2011;39(14):6201–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Department of Veterans Affairs (USA) Merit Review grants.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Oral Biology, College of Dentistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Inik Chang & Dong Min Shin

  2. Department of Urology, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan

    Shinichiro Fukuhara & Norio Nonomura

  3. Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA, 94121, USA

    Darryn K. Wong, Ankurpreet Gill, Yozo Mitsui, Shahana Majid, Sharanjot Saini, Soichiro Yamamura, Hiroshi Hirata, Koji Ueno, Sumit Arora, Varahram Shahryari, Guoren Deng, Kirsten L. Greene, Rajvir Dahiya & Yuichiro Tanaka

  4. Department of Urology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan

    Takeshi Chiyomaru & Hideki Enokida

  5. Department of Pathology, Veterans Affairs Medical Center and University of California, San Francisco, CA, 94121, USA

    Z. Laura Tabatabai

  6. Department of Urology, Shimane University Faculty of Medicine, Enya, 693-8501, Japan

    Hiroaki Shiina

  7. Department of Urology, University of California, 4150 Clement Street, San Francisco, CA, 94121, USA

    Yozo Mitsui, Shahana Majid, Sharanjot Saini, Soichiro Yamamura, Hiroshi Hirata, Koji Ueno, Guoren Deng, Kirsten L. Greene, Rajvir Dahiya & Yuichiro Tanaka

Authors
  1. Inik Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinichiro Fukuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Darryn K. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ankurpreet Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yozo Mitsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shahana Majid
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sharanjot Saini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Soichiro Yamamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takeshi Chiyomaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hiroshi Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Koji Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sumit Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Varahram Shahryari
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Guoren Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Z. Laura Tabatabai
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Kirsten L. Greene
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Dong Min Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Hideki Enokida
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Hiroaki Shiina
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Norio Nonomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Rajvir Dahiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Yuichiro Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Inik Chang or Yuichiro Tanaka.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chang, I., Fukuhara, S., Wong, D.K. et al. Cytochrome P450 1B1 polymorphisms and risk of renal cell carcinoma in men. Tumor Biol. 35, 10223–10230 (2014). https://doi.org/10.1007/s13277-014-2292-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2292-3

Keywords

Search

Navigation