Adipokine genes and prostate cancer risk

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
International Journal of Cancer (Impact Factor: 5.09). 02/2009; 124(4):869-76. DOI: 10.1002/ijc.24043
Source: PubMed


Adiposity and adipocyte-derived cytokines have been implicated in prostate carcinogenesis. However, the relationship of adipokine gene variants with prostate cancer risk has not been thoroughly investigated. We therefore examined common variants of the IL6, LEP, LEPR, TNF and ADIPOQ genes in relation to prostate cancer in a case-control study nested within a large cohort of Finnish men. The study sample consisted of 1,053 cases of prostate cancer, diagnosed over an average 11 years of follow up, and 1,053 controls matched to the cases on age, intervention group and date of baseline blood draw. Logistic regression was used to model the relative odds of prostate cancer. We also examined genotypes in relation to serum insulin, IGF-1 and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (-14858A>G, -13973A>C, -13736C>A) in a potential regulatory region of the LEP gene conferred a statistically significant 20% reduced risk of prostate cancer. For example, at the -14858A>G locus, heterozygotes and homozygotes for the A allele had an odds ratio (OR) of prostate cancer of 0.76 [95% confidence interval (CI) 0.62, 0.93] and 0.79 (95% CI 0.60, 1.04), respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; 95% CI 0.99,1.67; p(trend) = 0.05). Polymorphisms in the IL6, LEPR, TNF and ADIPOQ genes were not associated with prostate cancer. Allelic variants in the LEP gene are related to prostate cancer risk, supporting a role for leptin in prostate carcinogenesis.

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Available from: Susan T Mayne, Jul 18, 2014
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    • "First, significant heterogeneity were found for both of these two polymorphisms that may influence the interpretation of the results. Second, the individual sample sizes for cases of most studies included in the analysis were relatively small (<500) except for seven studies [25,27-29,34,36,39], and there were only one study based on the population of Latin Americans, Africans and Asians for the G2548A polymorphism, respectively, which did not provide insufficient statistical power to investigate the real association. Third, most of the studies used hospital-based controls that may result in some selection biases. "
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    ABSTRACT: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.
    PLoS ONE 10/2013; 8(10):e75135. DOI:10.1371/journal.pone.0075135 · 3.23 Impact Factor
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    • "The +45 T/G (rs2241766) (exon 2) and +276 G/T (rs1501299) (intron 2) polymorphisms in the ADIPOQ gene form a haplotype involved in obesity and insulin resistance [5] [6]. These LEP and ADIPOQ polymorphisms have been studied in non-Hodgkin lymphoma (NHL) as well as in prostate, esophagus and colorectal cancer (CRC); furthermore ADIPOQ polymorphisms have been studied in breast cancer [7] [8] [9] [10] [11] [12] [13]. The objective of this research was to analyze the association of polymorphisms A19G of LEP gene and +45 and +276 ADIPOQ gene in Mexican patients with CRC. "
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    ABSTRACT: Leptin and adiponectin are cytokines produced by adipose tissue with opposite effects on tumor growth: the former stimulate whereas the latter inhibit it. The objective was to analyze the association of LEP A19G and ADIPOQ+45 T/G and +276 G/T polymorphisms in Mexican patients with colorectal cancer (CRC). 68 unrelated patients with CRC (study group) and 102 blood donors (control group); all subjects were Mestizos from western Mexico. The polymorphisms were established by PCR-RFLP on DNA samples obtained from peripheral blood. The LEP A19G polymorphism showed significant differences between CRC patients and control group (p= 0.01 for G/A genotype and p= 0.02 for the recessive model G/G +G/A); yet, in the analysis stratified by gender, this difference remained significant only in males. The ADIPOQ polymorphisms did not shown any significant differences. Our results suggest that the A19G LEP polymorphism is associated with CRC in Mexican patients.
    Cancer biomarkers: section A of Disease markers 01/2010; 7(3):117-21. DOI:10.3233/CBM-2010-0154 · 1.72 Impact Factor
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    Signal Processing, 2004. Proceedings. ICSP '04. 2004 7th International Conference on; 01/2004
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