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Association between Toll-Like Receptor Gene Cluster (TLR6, TLR1, and TLR10) and Prostate Cancer

¹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; ² Department of Nutrition and ³ Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts and ⁴ Research Center for Genes, Environment, and Human Health, and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan

Requests for reprints: Yen-Ching Chen, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-2279; Fax: 617-525-2008. E-mail: karen.chen{at}channing.harvard.edu

Background: Chronic inflammation may be a risk factor for prostate cancer. Previously, we found significant associations between single nucleotide polymorphisms (SNPs) and haplotypes in Toll-like receptor (TLR) 4 and the risk of prostate cancer. TLR6, TLR1, and TLR10 are also involved in the pathogen-mediated inflammation pathway. A Swedish study observed associations between sequence variants in the TLR6-TLR1-TLR10 gene cluster and the risk of prostate cancer. We assessed if genetic polymorphisms of this gene cluster were associated with the risk of prostate cancer in a U.S. population.

Methods: In a nested case-control design within the Health Professionals Follow-Up Study, we identified 700 participants with prostate cancer who were diagnosed after they had provided a blood specimen in 1993 and by January 31, 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test. We genotyped 19 common (>5%) haplotype-tagging SNPs chosen from the SNPs discovered in a resequencing study spanning TLR6, TLR1, and TLR10 to test for the association between sequence variants cluster and prostate cancer.

Results: Neither individual SNPs nor common haplotypes in the three gene regions were associated with altered risk of prostate cancer or subgroups of aggressive prostate cancer. No effect modification was observed for age, body mass index, or family history of prostate cancer, except that TLR6_3649 showed nominally significant interaction with family history at the P < 0.05 level.

Conclusion: Inherited sequence variants of the innate immune gene cluster TLR6-TLR1-TLR10 were not appreciably associated with the risk of prostate cancer in this cohort. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1982–9)