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Polymorphisms in inflammatory genes, plasma antioxidants, and prostate cancer risk

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Abstract

Background

Presence of xenotropic murine leukemia virus–related virus and chronic inflammation in prostate tumor suggests that inflammation plays a role in prostate cancer etiology. This study investigated whether variants in inflammatory genes act alone or interact with plasma antioxidants to influence prostate cancer risk in a population-based case–control study in Central Arkansas.

Methods

Cases (n = 193) were men, aged 40–80, diagnosed with prostate cancer in three major hospitals in 1998–2003, and controls (n = 197) were matched to cases by age, race, and county of residence.

Results

After adjustment for confounders, polymorphisms in COX-2 (rs689466) and IL-8 (rs4073) were not significantly associated with prostate cancer risk. However, apparent interactions were observed between these genetic variants and plasma antioxidants on the risk of this malignancy. The protective effect of the mutant allele of the COX-2 polymorphism was more pronounced among subjects with high plasma levels of β-cryptoxanthin, lycopene, β-carotene, or selenium (≥median) [e.g., OR (95% CI): 0.37 (0.15, 0.86) (AG/GG vs. AA) for β-cryptoxanthin]. Conversely, the promoting effect of the variant allele of the IL-8 polymorphism was more remarkable in subjects with low plasma levels of Lutein/zeaxanthin, β-cryptoxanthin, and β-carotene (<median) [e.g., OR (95% CI): 2.44 (1.08, 5.75) (AT/TT vs. AA) for β-carotene].

Conclusions

We found that sequence variants in inflammatory genes interact with plasma antioxidants to modulate prostate cancer risk.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. American Cancer Society (2009) Cancer facts & figures. American Cancer Society, Atlanta

    Google Scholar 

  3. Li H, Kantoff PW, Giovannucci E et al (2005) Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer. Cancer Res 65:2498–2504

    Article  CAS  PubMed  Google Scholar 

  4. van Gils CH, Bostick RM, Stern MC, Taylor JA (2002) Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene. Cancer Epidemiol Biomarkers Prev 11:1279–1284

    PubMed  Google Scholar 

  5. De Marzo AM, Marchi VL, Epstein JI, Nelson WG (1999) Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol 155:1985–1992

    PubMed  Google Scholar 

  6. Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR (2009) XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. Proc Natl Acad Sci USA 106:16351–16356

    Article  CAS  PubMed  Google Scholar 

  7. Dennis LK, Lynch CF, Torner JC (2002) Epidemiologic association between prostatitis and prostate cancer. Urology 60:78–83

    Article  PubMed  Google Scholar 

  8. Dennis LK, Dawson DV (2002) Meta-analysis of measures of sexual activity and prostate cancer. Epidemiology 13:72–79

    Article  PubMed  Google Scholar 

  9. Mahmud S, Franco E, Aprikian A (2004) Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. Br J Cancer 90:93–99

    Article  CAS  PubMed  Google Scholar 

  10. De Marzo AM, Platz EA, Sutcliffe S et al (2007) Inflammation in prostate carcinogenesis. Nat Rev Cancer 7:256–269

    Article  PubMed  Google Scholar 

  11. Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11:1513–1530

    CAS  PubMed  Google Scholar 

  12. Xu J, Zheng SL, Turner A et al (2002) Associations between hOGG1 sequence variants and prostate cancer susceptibility. Cancer Res 62:2253–2257

    CAS  PubMed  Google Scholar 

  13. Stone A, Ratnasinghe LD, Emerson GL et al (2005) CYP3A43 Pro(340)Ala polymorphism and prostate cancer risk in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 14:1257–1261

    Article  CAS  PubMed  Google Scholar 

  14. Zhang J, Dhakal IB, Greene G, Lang NP, Kadlubar FF (2010) Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants. Urology 75:779–785

    Article  PubMed  Google Scholar 

  15. El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H (2002) Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. Am J Clin Nutr 76:172–179

    CAS  PubMed  Google Scholar 

  16. Platz EA, De Marzo AM (2004) Epidemiology of inflammation and prostate cancer. J Urol 171(2 Pt 2):S36–S40

    Article  PubMed  Google Scholar 

  17. McCarron SL, Edwards S, Evans PR et al (2002) Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 62:3369–3372

    CAS  PubMed  Google Scholar 

  18. Bidwell J, Keen L, Gallagher G et al (2001) Cytokine gene polymorphism in human disease: on-line databases, supplement 1. Genes Immun 2:61–70

    Article  CAS  PubMed  Google Scholar 

  19. Nelson WG, De Marzo AM, DeWeese TL, Isaacs WB (2004) The role of inflammation in the pathogenesis of prostate cancer. J Urol 172(5 Pt 2):S6–S11 discussion S11-12

    Article  CAS  PubMed  Google Scholar 

  20. Cheng I, Liu X, Plummer SJ, Krumroy LM, Casey G, Witte JS (2007) COX2 genetic variation, NSAIDs, and advanced prostate cancer risk. Br J Cancer 97:557–561

    Article  CAS  PubMed  Google Scholar 

  21. Zhang X, Miao X, Tan W et al (2005) Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology 129:565–576

    CAS  PubMed  Google Scholar 

  22. Koch AE, Polverini PJ, Kunkel SL et al (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801

    Article  CAS  PubMed  Google Scholar 

  23. Kim SJ, Uehara H, Karashima T, McCarty M, Shih N, Fidler IJ (2001) Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice. Neoplasia 3:33–42

    Article  CAS  PubMed  Google Scholar 

  24. Inoue K, Slaton JW, Eve BY et al (2000) Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer. Clin Cancer Res 6:2104–2119

    CAS  PubMed  Google Scholar 

  25. Veltri RW, Miller MC, Zhao G et al (1999) Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer. Urology 53:139–147

    Article  CAS  PubMed  Google Scholar 

  26. Michaud DS, Daugherty SE, Berndt SI et al (2006) Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer. Cancer Res 66:4525–4530

    Article  CAS  PubMed  Google Scholar 

  27. Hull J, Thomson A, Kwiatkowski D (2000) Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax 55:1023–1027

    Article  CAS  PubMed  Google Scholar 

  28. Zhang J, Dhakal I, Stone A et al (2007) Plasma carotenoids and prostate cancer: a population-based case-control study in Arkansas. Nutr Cancer 59:46–53

    CAS  PubMed  Google Scholar 

  29. Guo Y, Zhang X, Tan W et al (2007) Platelet 12-lipoxygenase Arg261Gln polymorphism: functional characterization and association with risk of esophageal squamous cell carcinoma in combination with COX-2 polymorphisms. Pharmacogenet Genomics 17:197–205

    Article  CAS  PubMed  Google Scholar 

  30. Saenz-Lopez P, Carretero R, Cozar JM et al (2008) Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer. BMC Cancer 8:382

    Article  PubMed  Google Scholar 

  31. Danforth KN, Rodriguez C, Hayes RB et al (2008) TNF polymorphisms and prostate cancer risk. Prostate 68:400–407

    Article  CAS  PubMed  Google Scholar 

  32. Moore SC, Leitzmann MF, Albanes D et al (2009) Adipokine genes and prostate cancer risk. Int J Cancer 124:869–876

    Article  CAS  PubMed  Google Scholar 

  33. Pierce BL, Biggs ML, DeCambre M et al (2009) C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older. Cancer Causes Control 20:1193–1203

    Article  PubMed  Google Scholar 

  34. Sun J, Hedelin M, Zheng SL et al (2004) Interleukin-6 sequence variants are not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 13:1677–1679

    CAS  PubMed  Google Scholar 

  35. Stark JR, Li H, Kraft P et al (2009) Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality. Int J Cancer 124:2683–2689

    Article  CAS  PubMed  Google Scholar 

  36. Willett WC, Lenart E (1998) Reproducibility and validity of food-frequency questionnaire. In: Willett WC (ed) Nutritional epidemiology, 2nd edn. Oxford University Press, New York, NY, pp 101–147

    Google Scholar 

  37. Hughes C, Murphy A, Martin C, Sheils O, O’Leary J (2005) Molecular pathology of prostate cancer. J Clin Pathol 58:673–684

    Article  CAS  PubMed  Google Scholar 

  38. Comstock GW, Alberg AJ, Helzlsouer KJ (1993) Reported effects of long-term freezer storage on concentrations of retinol, beta-carotene, and alpha-tocopherol in serum or plasma summarized. Clin Chem 39:1075–1078

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported by a fund from the Arkansas Department of Health (Dr. Zhang, PI) and a grant from the National Institute on Aging, NIH (1R01AG15722, Dr. Lang, PI). We are grateful to Angie Stone for her assistance in DNA extraction and genotyping.

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Authors and Affiliations

  1. Department of Public Health, Indiana University School of Medicine, 714 N. Senate Avenue, Suite EF250, Indianapolis, IN, 46202, USA

    Jianjun Zhang

  2. Division of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Ishwori B. Dhakal & Fred F. Kadlubar

  3. Department of Surgery, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Nicholas P. Lang

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  1. Jianjun Zhang
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  2. Ishwori B. Dhakal
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  3. Nicholas P. Lang
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  4. Fred F. Kadlubar
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Correspondence to Jianjun Zhang.

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Zhang, J., Dhakal, I.B., Lang, N.P. et al. Polymorphisms in inflammatory genes, plasma antioxidants, and prostate cancer risk. Cancer Causes Control 21, 1437–1444 (2010). https://doi.org/10.1007/s10552-010-9571-0

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  • DOI: https://doi.org/10.1007/s10552-010-9571-0

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