Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk

F. Lindmark, S. L. Zheng, F. Wiklund, K. A. Bälter, J. Sun, B. Chang, M. Hedelin, J. Clark, J. E. Johansson, D. A. Meyers, H. O. Adami, William B Isaacs, H. Grönberg, J. Xu

Research output: Contribution to journalArticle

Abstract

IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1α and IL1β. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR = 1.0, 95% CI =0.8-1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3-2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.

Original languageEnglish (US)
Pages (from-to)493-497
Number of pages5
JournalBritish Journal of Cancer
Volume93
Issue number4
DOIs
StatePublished - Aug 22 2005

Fingerprint

Interleukin-1 Receptors
Haplotypes
Prostatic Neoplasms
Odds Ratio
Single Nucleotide Polymorphism
Confidence Intervals
Cytokines
Genes
Inflammation
Genetic Models
Sweden
Population
Case-Control Studies
Anti-Inflammatory Agents
Genotype

Keywords

  • Association
  • IL1-RN
  • Inflammation
  • Prostate cancer
  • SNPs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lindmark, F., Zheng, S. L., Wiklund, F., Bälter, K. A., Sun, J., Chang, B., ... Xu, J. (2005). Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk. British Journal of Cancer, 93(4), 493-497. https://doi.org/10.1038/sj.bjc.6602729

Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk. / Lindmark, F.; Zheng, S. L.; Wiklund, F.; Bälter, K. A.; Sun, J.; Chang, B.; Hedelin, M.; Clark, J.; Johansson, J. E.; Meyers, D. A.; Adami, H. O.; Isaacs, William B; Grönberg, H.; Xu, J.

In: British Journal of Cancer, Vol. 93, No. 4, 22.08.2005, p. 493-497.

Research output: Contribution to journalArticle

Lindmark, F, Zheng, SL, Wiklund, F, Bälter, KA, Sun, J, Chang, B, Hedelin, M, Clark, J, Johansson, JE, Meyers, DA, Adami, HO, Isaacs, WB, Grönberg, H & Xu, J 2005, 'Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk', British Journal of Cancer, vol. 93, no. 4, pp. 493-497. https://doi.org/10.1038/sj.bjc.6602729
Lindmark F, Zheng SL, Wiklund F, Bälter KA, Sun J, Chang B et al. Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk. British Journal of Cancer. 2005 Aug 22;93(4):493-497. https://doi.org/10.1038/sj.bjc.6602729
Lindmark, F. ; Zheng, S. L. ; Wiklund, F. ; Bälter, K. A. ; Sun, J. ; Chang, B. ; Hedelin, M. ; Clark, J. ; Johansson, J. E. ; Meyers, D. A. ; Adami, H. O. ; Isaacs, William B ; Grönberg, H. ; Xu, J. / Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk. In: British Journal of Cancer. 2005 ; Vol. 93, No. 4. pp. 493-497.
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abstract = "IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1α and IL1β. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95{\%} of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7{\%}) compared to controls (33.5{\%}) (haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR) = 1.6, 95{\%} confidence interval (CI) = 1.2-2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR = 1.0, 95{\%} CI =0.8-1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95{\%} CI = 1.3-2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.",
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AU - Lindmark, F.

AU - Zheng, S. L.

AU - Wiklund, F.

AU - Bälter, K. A.

AU - Sun, J.

AU - Chang, B.

AU - Hedelin, M.

AU - Clark, J.

AU - Johansson, J. E.

AU - Meyers, D. A.

AU - Adami, H. O.

AU - Isaacs, William B

AU - Grönberg, H.

AU - Xu, J.

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N2 - IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1α and IL1β. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR = 1.0, 95% CI =0.8-1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3-2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.

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