Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer

Bushley, Abigail W.; Ferrell, Robert E.; McDuffie, Katharine; Terada, Keith Y.; Carney, Michael E.; Thompson, Pamela J.; Wilkens, Lynne R.; Tung, Ko Hui; Ness, Roberta B.; Goodman, Marc T.

doi:10.1016/j.ygyno.2004.08.024

Cited by 70 publications

(58 citation statements)

References 29 publications

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“…This hypothesis was sustained by a study of cytokine gene polymorphism, which related the IL-18 G137C variant to ovarian cancer development. 39 However, we previously reported that ovarian tumor cell lines or primary cultures from advanced ovarian cancer show defective IL-18 processing to its mature form and spontaneously release biologically inactive pro-IL-18.…”

Section: Tumor Immunologymentioning

confidence: 98%

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Orengo

Fabbi

Miglietta

et al. 2011

Intl Journal of Cancer

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Interleukin (IL)-18 is a proinflammatory and immune-enhancing cytokine, which exerts antitumor effects in vivo, mediated by the induction of interferon (IFN)c. We previously reported that IL-18 processing is defective in epithelial ovarian carcinoma (EOC) cells, which secrete an inactive precursor (pro-IL-18) in vitro. In addition, IL-18 was reported as a potential biomarker of EOC. Here, we further investigated its role as a serological marker in human EOC and addressed its possible biological activity in vivo. Our data indicate that immunoreactive IL-18 is increased in EOC patients' sera at diagnosis as compared with age-matched healthy women. IL-18 levels were higher in the ascitic fluids than in sera, suggesting a local production in the peritoneal cavity. Indeed, immunohistochemical analysis of tumors showed IL-18 expression in cytokeratine-positive neoplastic cells, although also scattered histiocytes and some lymphoid cells stained for IL-18. The detection of human IL-18 in sera and ascitic fluids of immunodeficient mice, orthotopically implanted with human EOC cells, further suggested that circulating IL-18 is tumor-derived. However, IL-18 is not an EOC specific biomarker, as increased serum levels were found also in some endometrial cancer patients. By means of a new monoclonal antibody, we characterized IL-18 present in the ascitic fluid as pro-IL-18, which is biologically inactive. Accordingly, IFNc was not increased in EOC patients' sera and ascitic fluids and showed no correlation with IL-18 levels. Altogether these data indicate that IL-18 in EOC fluids is predominantly tumor-derived and that its lack of biological activity may represent a mechanism of tumor-escape.

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Section: Tumor Immunologymentioning

confidence: 98%

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Orengo

Fabbi

Miglietta

et al. 2011

Intl Journal of Cancer

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“…A total of 73 studies from 68 eligible articles, involving 15,942 cancer cases and 22,336 controls, were identified that had investigated the association between the IL-10 -819C/T polymorphism and the risk for cancer Alonso et al, 2005;AlpizarAlpizar et al, 2005;Amirzargar et al, 2005;Ando et al, 2009;Basturk et al, 2005;Bushley et al, 2004;Cacev et al, 2008;Castro et al, 2009;Colakogullari et al, 2008;Cozar et al, 2007;Crivello et al, 2006;Crusius et al, 2008;da Silva et al, 2007; FIG. 1.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

The Interleukin 10 −819C/T Polymorphism and Cancer Risk: A HuGE Review and Meta-Analysis of 73 Studies Including 15,942 Cases and 22,336 Controls

Liu²,

Huang

et al. 2013

OMICS: A Journal of Integrative Biology

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The aim of the present work was to perform a meta-analysis to evaluate the association between the interleukin 10 (IL-10) -819C/T (rs1800871) polymorphism and cancer risk. A total of 73 studies, including 15,942 cancer cases and 22,336 controls, were identified in this meta-analysis. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Overall, no significant association was identified between the IL-10 -819C/T polymorphism and cancer risk. In the subgroup analyses, the T allele and TT genotype were associated with a moderately reduced cancer risk in the Asian population (T allele vs. Individuals who were homozygous for the T allele (TT) were found to be associated with significantly reduced gastric cancer risk in the Asian population. The heterozygous variant (CT) and the dominant model (TT/CT vs. CC) were associated with an increased risk for cervical and ovarian cancer. However, the IL-10 -819C/T polymorphism was not significantly associated with breast cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, prostate cancer, lymphoma, or melanoma. The depressed cancer risk of the TT genotype occurred in the studies of hospital-based case-control studies and the studies recruited less than 500 subjects, but no statistically significant results were found in the stratified analyses using genotyping method. The results suggest that the IL-10 -819TT genotype may be a protective factor for cancer in Asians, especially gastric cancer. In contrast, the CT genotype and the dominant model could be risk factors for cervical and ovarian cancer. The importance of stratifying by ethnicity, cancer type, study design, and sample size needs to be standardized in future studies, together with considering the association between the IL-10 -819C/T polymorphism and cancer risk. Furthermore, the linkage of -819C/T with other polymorphisms of the IL-10 gene may help explain the variability in findings.

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“…Investigation has revealed the relationship between IL-18 gene polymorphic variants and predisposition to various malignant viral and autoimmune diseases [22][23][24][25][26][27][28][29][30][31][32][33]. Recently, a significant association was found between SLE and the IL-18 105 A>C (rs549908) polymorphic variants [32].…”

Section: Introductionmentioning

confidence: 99%

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

et al. 2009

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SummarySystemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by various aberrations including increased production of IL-18.Since IL-18 105 A>C polymorphic variants have been linked to increased production of this cytokine, we investigated the prevalence of IL-18 105 A>C (rs549908) polymorphic variants in SLE patients (n=111) and controls (n=152).There were no significant differences in the distribution of IL-18 105 A>C polymorphic variants in SLE patients and controls. However, there was a significant association between the IL-18 105 AA genotype (recessive model) and renal manifestations OR=3.360 (1.523-7.415, P=0.0039) and the P value remained statistically significant after Bonferroni correction (P corr = 0.0351).Our findings indicate that the IL-18 105 AA genotype variant can contribute to renal manifestations in patients with SLE.

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Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer

Cited by 70 publications

References 29 publications

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

The Interleukin 10 −819C/T Polymorphism and Cancer Risk: A HuGE Review and Meta-Analysis of 73 Studies Including 15,942 Cases and 22,336 Controls

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

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