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Genetic variation in the COX-2 gene and the association with prostate cancer risk.

https://arctichealth.org/en/permalink/ahliterature16449
Source
Int J Cancer. 2006 Feb 27;
Publication Type
Article
Date
Feb-27-2006
Author
K. Shahedi
S. Lindström
S L Zheng
F. Wiklund
J. Adolfsson
J. Sun
K. Augustsson-Bälter
B-L Chang
H-O Adami
W. Liu
H. Grönberg
J. Xu
Author Affiliation
Department of Radiation Sciences, Oncology, University of Umeå Umeå Sweden.
Source
Int J Cancer. 2006 Feb 27;
Date
Feb-27-2006
Language
English
Publication Type
Article
Abstract
COX-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation and pain response in different tissues in the body. Accumulating evidence from epidemiologic studies, chemical carcinogen-induced rodent models and clinical trials indicate that COX-2 plays a role in human carcinogenesis and is overexpressed in prostate cancer tissue. We examined whether sequence variants in the COX-2 gene are associated with prostate cancer risk. We analyzed a large population-based case-control study, cancer prostate in Sweden (CAPS) consisting of 1,378 cases and 782 controls. We evaluated 16 single nucleotide polymorphisms (SNPs) spanning the entire COX-2 gene in 94 subjects of the control group. Five SNPs had a minor allele frequency of more than 5% in our study population and these were genotyped in all case patients and control subjects and gene-specific haplotypes were constructed. A statistically significant difference in allele frequency between cases and controls was observed for 2 of the SNPs (+3100 T/G and +8365 C/T), with an odds ratio of 0.78 (95% CI = 0.64-0.96) and 0.65 (95% CI = 0.45-0.94) respectively. In the haplotype analysis, 1 haplotype carrying the variant allele from both +3100 T/G and +8365 C/T, with a population frequency of 3%, was also significantly associated with decreased risk of prostate cancer (p = 0.036, global simulated p-value = 0.046). This study supports the hypothesis that inflammation is involved in prostate carcinogenesis and that sequence variation within the COX-2 gene influence the risk of prostate cancer. (c) 2006 Wiley-Liss, Inc.
PubMed ID
16506214 View in PubMed
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Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk.

https://arctichealth.org/en/permalink/ahliterature16835
Source
Br J Cancer. 2005 Aug 22;93(4):493-7
Publication Type
Article
Date
Aug-22-2005
Author
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
W. Isaacs
H. Grönberg
J. Xu
Author Affiliation
Department of Radiation Sciences/Oncology, Umeå University, Sweden.
Source
Br J Cancer. 2005 Aug 22;93(4):493-7
Date
Aug-22-2005
Language
English
Publication Type
Article
Keywords
Aged
Case-Control Studies
Genotype
Haplotypes
Humans
Inflammation - genetics
Male
Odds Ratio
Polymorphism, Single Nucleotide
Prostatic Neoplasms - genetics - immunology
Risk factors
Sialoglycoproteins - genetics - physiology
Sweden
Variation (Genetics)
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 IL1alpha and IL1beta. 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.
PubMed ID
16106254 View in PubMed
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