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Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk.
J Natl Cancer Inst. 2005 Apr 06; 97(7):525-32.JNCI

Abstract

BACKGROUND

Chronic inflammation plays an important role in several human cancers and may be involved in the etiology of prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross-talk between innate immunity and adaptive immunity. Our previous finding of an association of TLR4 gene sequence variants and prostate cancer risk provides evidence for a role of TLRs in prostate cancer. In this study, we investigated whether sequence variants in the TLR6-TLR1-TLR10 gene cluster, residing within a 54-kb region on 4p14, were associated with prostate cancer risk.

METHODS

We selected 32 single-nucleotide polymorphisms (SNPs) covering these three genes and genotyped these SNPs in 96 control subjects from the Cancer Prostate in Sweden (CAPS) population-based prostate cancer case-control study. Five distinct haplotype blocks were inferred at this region, and we identified 17 haplotype-tagging SNPs (htSNPs) that could uniquely describe >95% of the haplotypes. These 17 htSNPs were then genotyped in the entire CAPS study population (1383 case subjects and 780 control subjects). Odds ratios of prostate cancer for the carriers of a variant allele versus those with the wild-type allele were estimated using unconditional logistic regression.

RESULTS

The allele frequencies of 11 of the 17 SNPs were statistically significantly different between case and control subjects (P = .04-.001), with odds ratios for variant allele carriers (homozygous or heterozygous) compared with wild-type allele carriers ranging from 1.20 (95% confidence interval [CI] = 1.00 to 1.43) to 1.38 (95% CI = 1.12 to 1.70). Phylogenetic tree analyses of common haplotypes identified a clade of two evolutionarily related haplotypes that are statistically significantly associated with prostate cancer risk. These two haplotypes contain all the risk alleles of these 11 associated SNPs.

CONCLUSION

The observed multiple associated SNPs at the TLR6-TLR1-TLR10 gene cluster were dependent and suggest the presence of a founder prostate cancer risk variant on this haplotype background. The TLR6-TLR1-TLR10 gene cluster may play a role in prostate cancer risk, although further functional studies are needed to pinpoint the disease-associated variants in this gene cluster.

Authors+Show Affiliations

Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15812078

Citation

Sun, Jielin, et al. "Sequence Variants in Toll-like Receptor Gene Cluster (TLR6-TLR1-TLR10) and Prostate Cancer Risk." Journal of the National Cancer Institute, vol. 97, no. 7, 2005, pp. 525-32.
Sun J, Wiklund F, Zheng SL, et al. Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. J Natl Cancer Inst. 2005;97(7):525-32.
Sun, J., Wiklund, F., Zheng, S. L., Chang, B., Bälter, K., Li, L., Johansson, J. E., Li, G., Adami, H. O., Liu, W., Tolin, A., Turner, A. R., Meyers, D. A., Isaacs, W. B., Xu, J., & Grönberg, H. (2005). Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. Journal of the National Cancer Institute, 97(7), 525-32.
Sun J, et al. Sequence Variants in Toll-like Receptor Gene Cluster (TLR6-TLR1-TLR10) and Prostate Cancer Risk. J Natl Cancer Inst. 2005 Apr 6;97(7):525-32. PubMed PMID: 15812078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. AU - Sun,Jielin, AU - Wiklund,Fredrik, AU - Zheng,S Lilly, AU - Chang,Baoli, AU - Bälter,Katarina, AU - Li,Liwu, AU - Johansson,Jan-Erik, AU - Li,Ge, AU - Adami,Hans-Olov, AU - Liu,Wennuan, AU - Tolin,Amy, AU - Turner,Aubrey R, AU - Meyers,Deborah A, AU - Isaacs,William B, AU - Xu,Jianfeng, AU - Grönberg,Henrik, PY - 2005/4/7/pubmed PY - 2005/4/13/medline PY - 2005/4/7/entrez SP - 525 EP - 32 JF - Journal of the National Cancer Institute JO - J Natl Cancer Inst VL - 97 IS - 7 N2 - BACKGROUND: Chronic inflammation plays an important role in several human cancers and may be involved in the etiology of prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross-talk between innate immunity and adaptive immunity. Our previous finding of an association of TLR4 gene sequence variants and prostate cancer risk provides evidence for a role of TLRs in prostate cancer. In this study, we investigated whether sequence variants in the TLR6-TLR1-TLR10 gene cluster, residing within a 54-kb region on 4p14, were associated with prostate cancer risk. METHODS: We selected 32 single-nucleotide polymorphisms (SNPs) covering these three genes and genotyped these SNPs in 96 control subjects from the Cancer Prostate in Sweden (CAPS) population-based prostate cancer case-control study. Five distinct haplotype blocks were inferred at this region, and we identified 17 haplotype-tagging SNPs (htSNPs) that could uniquely describe >95% of the haplotypes. These 17 htSNPs were then genotyped in the entire CAPS study population (1383 case subjects and 780 control subjects). Odds ratios of prostate cancer for the carriers of a variant allele versus those with the wild-type allele were estimated using unconditional logistic regression. RESULTS: The allele frequencies of 11 of the 17 SNPs were statistically significantly different between case and control subjects (P = .04-.001), with odds ratios for variant allele carriers (homozygous or heterozygous) compared with wild-type allele carriers ranging from 1.20 (95% confidence interval [CI] = 1.00 to 1.43) to 1.38 (95% CI = 1.12 to 1.70). Phylogenetic tree analyses of common haplotypes identified a clade of two evolutionarily related haplotypes that are statistically significantly associated with prostate cancer risk. These two haplotypes contain all the risk alleles of these 11 associated SNPs. CONCLUSION: The observed multiple associated SNPs at the TLR6-TLR1-TLR10 gene cluster were dependent and suggest the presence of a founder prostate cancer risk variant on this haplotype background. The TLR6-TLR1-TLR10 gene cluster may play a role in prostate cancer risk, although further functional studies are needed to pinpoint the disease-associated variants in this gene cluster. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/15812078/Sequence_variants_in_Toll_like_receptor_gene_cluster__TLR6_TLR1_TLR10__and_prostate_cancer_risk_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/dji070 DB - PRIME DP - Unbound Medicine ER -