H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer

Fredrik Lindmark, S. Lilly Zheng, Fredrik Wiklund, Jeannette Bensen, Katarina Augustsson Bälter, Baoli Chang, Maria Hedelin, Jonathan Clark, Pär Stattin, Deborah A. Meyers, Hans Olov Adami, William B Isaacs, Henrik Grönberg, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor β superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer. Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A statistically significant difference (P = .006) in genotype frequency was observed for the nonsynonymous change H6D (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95 % CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer. Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.

Original languageEnglish (US)
Pages (from-to)1248-1254
Number of pages7
JournalJournal of the National Cancer Institute
Volume96
Issue number16
DOIs
StatePublished - Aug 18 2004

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Growth Differentiation Factor 15
Prostatic Neoplasms
Genes
Genotype
Haplotypes
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Population
Inflammation
Transforming Growth Factors
Histidine
Sweden
Aspartic Acid
Case-Control Studies
Neoplasms
Logistic Models
Macrophages
Regression Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lindmark, F., Zheng, S. L., Wiklund, F., Bensen, J., Bälter, K. A., Chang, B., ... Xu, J. (2004). H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer. Journal of the National Cancer Institute, 96(16), 1248-1254. https://doi.org/10.1093/jnci/djh227

H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer. / Lindmark, Fredrik; Zheng, S. Lilly; Wiklund, Fredrik; Bensen, Jeannette; Bälter, Katarina Augustsson; Chang, Baoli; Hedelin, Maria; Clark, Jonathan; Stattin, Pär; Meyers, Deborah A.; Adami, Hans Olov; Isaacs, William B; Grönberg, Henrik; Xu, Jianfeng.

In: Journal of the National Cancer Institute, Vol. 96, No. 16, 18.08.2004, p. 1248-1254.

Research output: Contribution to journalArticle

Lindmark, F, Zheng, SL, Wiklund, F, Bensen, J, Bälter, KA, Chang, B, Hedelin, M, Clark, J, Stattin, P, Meyers, DA, Adami, HO, Isaacs, WB, Grönberg, H & Xu, J 2004, 'H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer', Journal of the National Cancer Institute, vol. 96, no. 16, pp. 1248-1254. https://doi.org/10.1093/jnci/djh227
Lindmark, Fredrik ; Zheng, S. Lilly ; Wiklund, Fredrik ; Bensen, Jeannette ; Bälter, Katarina Augustsson ; Chang, Baoli ; Hedelin, Maria ; Clark, Jonathan ; Stattin, Pär ; Meyers, Deborah A. ; Adami, Hans Olov ; Isaacs, William B ; Grönberg, Henrik ; Xu, Jianfeng. / H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer. In: Journal of the National Cancer Institute. 2004 ; Vol. 96, No. 16. pp. 1248-1254.
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abstract = "Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor β superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer. Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95{\%} confidence intervals (CIs). Results: A statistically significant difference (P = .006) in genotype frequency was observed for the nonsynonymous change H6D (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95{\%} CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95 {\%} CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2{\%} for sporadic cancer and 19.2{\%} for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer. Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.",
author = "Fredrik Lindmark and Zheng, {S. Lilly} and Fredrik Wiklund and Jeannette Bensen and B{\"a}lter, {Katarina Augustsson} and Baoli Chang and Maria Hedelin and Jonathan Clark and P{\"a}r Stattin and Meyers, {Deborah A.} and Adami, {Hans Olov} and Isaacs, {William B} and Henrik Gr{\"o}nberg and Jianfeng Xu",
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AU - Lindmark, Fredrik

AU - Zheng, S. Lilly

AU - Wiklund, Fredrik

AU - Bensen, Jeannette

AU - Bälter, Katarina Augustsson

AU - Chang, Baoli

AU - Hedelin, Maria

AU - Clark, Jonathan

AU - Stattin, Pär

AU - Meyers, Deborah A.

AU - Adami, Hans Olov

AU - Isaacs, William B

AU - Grönberg, Henrik

AU - Xu, Jianfeng

PY - 2004/8/18

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N2 - Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor β superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer. Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A statistically significant difference (P = .006) in genotype frequency was observed for the nonsynonymous change H6D (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95 % CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer. Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.

AB - Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor β superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer. Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A statistically significant difference (P = .006) in genotype frequency was observed for the nonsynonymous change H6D (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95 % CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer. Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.

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