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 & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Jielin SunHenrik Grönberg

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 ...Continue Reading

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