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.
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.
Authors: Arnold I Chin; Andrea K Miyahira; Anthony Covarrubias; Juli Teague; Beichu Guo; Paul W Dempsey; Genhong Cheng Journal: Cancer Res Date: 2010-03-16 Impact factor: 12.701
Authors: Mark P Purdue; Qing Lan; Sophia S Wang; Anne Kricker; Idan Menashe; Tong-Zhang Zheng; Patricia Hartge; Andrew E Grulich; Yawei Zhang; Lindsay M Morton; Claire M Vajdic; Theodore R Holford; Richard K Severson; Brian P Leaderer; James R Cerhan; Meredith Yeager; Wendy Cozen; Kevin Jacobs; Scott Davis; Nathaniel Rothman; Stephen J Chanock; Nilanjan Chatterjee; Bruce K Armstrong Journal: Carcinogenesis Date: 2008-11-24 Impact factor: 4.944
Authors: Sara Lindström; David J Hunter; Henrik Grönberg; Pär Stattin; Fredrik Wiklund; Jianfeng Xu; Stephen J Chanock; Richard Hayes; Peter Kraft Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-03-03 Impact factor: 4.254
Authors: Callie M Thompson; Tarah D Holden; Gail Rona; Balaji Laxmanan; R Anthony Black; Grant E OʼKeefe; Mark M Wurfel Journal: Ann Surg Date: 2014-01 Impact factor: 12.969