Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the Toll-like receptor 6-1-10 gene cluster increase prostate cancer risk

Jielin Sun, Fredrik Wiklund, Fang Chi Hsu, Katarina Bälter, S. Lilly Zheng, Jan Erik Johansson, Baoli Chang, Wennuan Liu, Tao Li, Aubrey R. Turner, Liwu Li, Ge Li, Hans Olov Adami, William B Isaacs, Jianfeng Xu, Henrik Grönberg

Research output: Contribution to journalArticle

Abstract

Chronic or recurrent inflammation has been suggested as a causal factor in several human malignancies, including prostate cancer. Genetic predisposition is also a strong risk factor in the development of prostate cancer. In particular, Toll-like receptors (TLR), especially the TLR6-1-10 gene cluster, are involved in prostate cancer development. Interleukin-1 receptor-associated kinases (IRAK) 1 and 4 are critical components in the TLR signaling pathway. In this large case-control study, we tested two hypotheses: (a) sequence variants in IRAK1 and IRAK4 are associated with prostate cancer risk and (b) sequence variants in IRAK1/4 and TLR1-6-10 interacts and confers a stronger risk to prostate cancer. We analyzed 11 single nucleotide polymorphisms (four in IRAK1 and seven in IRAK4) among 1,383 newly diagnosed prostate cancer patients and 780 population controls in Sweden. Although the single-nucleotide polymorphisms in IRAK1 and IRAK4 alone were not significantly associated with prostate cancer risk, one single-nucleotide polymorphism in IRAK4, when combined with the high-risk genotype at TLR6-1-10, conferred a significant excess risk of prostate cancer. In particular, men with the risk genotype at TLR6-1-10 and IRAK4-7987 CG/CC had an odds ratio of 9.68 (P = 0.03) when compared with men who had wild-type genotypes. Our findings suggest synergistic effects between sequence variants in IRAK4 and the TLR 6-1-10 gene cluster. Although this study was based on a priori hypothesis and was designed to address many common issues facing this type of study, our results need confirmation in even larger studies.

Original languageEnglish (US)
Pages (from-to)480-485
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number3
DOIs
StatePublished - Mar 2006

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Sun, J., Wiklund, F., Hsu, F. C., Bälter, K., Zheng, S. L., Johansson, J. E., Chang, B., Liu, W., Li, T., Turner, A. R., Li, L., Li, G., Adami, H. O., Isaacs, W. B., Xu, J., & Grönberg, H. (2006). Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the Toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. Cancer Epidemiology Biomarkers and Prevention, 15(3), 480-485. https://doi.org/10.1158/1055-9965.EPI-05-0645