Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals

Navaglia, Filippo; Basso, Daniela; Zambon, Carlo–Federico; Ponzano, E.; Caenazzo, Luciana; Gallo, Nicoletta; Falda, Alessandra; Belluco, Claudio; Fogar, Paola; Greco, Eliana; Mario, F. Di; Rugge, Massimo; Plebani, Mario

doi:10.1136/jmg.2004.022723

Cited by 38 publications

(25 citation statements)

References 40 publications

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“…In this context it is, however, noteworthy that accumulating evidence would seem to suggest that IL-12 and IL-23 are important mediators in the process that links H pylori infection to gastric cancer. Indeed, polymorphisms of IL-12p40 and p35 genes enhance the risk of non-cardia gastric cancers in H pyloriinfected patients [53] . Moreover, high levels of IL-23 have been documented in human gastric cancers [53] .…”

Section: H Pylori-driven Th1-immune Responsementioning

confidence: 99%

“…Indeed, polymorphisms of IL-12p40 and p35 genes enhance the risk of non-cardia gastric cancers in H pyloriinfected patients [53] . Moreover, high levels of IL-23 have been documented in human gastric cancers [53] . Nonetheless, no functional study has so far mechanistically linked the activity of IL-12 and IL-23 to gastric cancer.…”

Section: H Pylori-driven Th1-immune Responsementioning

confidence: 99%

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Emerging role of IL-23/IL-17 axis inH pylori-associated pathology

Caruso¹

2007

WJG

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Section: H Pylori-driven Th1-immune Responsementioning

confidence: 99%

Section: H Pylori-driven Th1-immune Responsementioning

confidence: 99%

Emerging role of IL-23/IL-17 axis inH pylori-associated pathology

Caruso¹

2007

WJG

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“…IL-12 has previously been implicated in the development of malignant tumors, e.g. Helicobacter pylori -associated gastric cancer [31], HPV-related cervical carcinoma [32], hepatocellular carcinoma [33], and brain tumors [34]. The role of IL-12 in ileal carcinoid development remains to be elucidated, but the data suggest that inflammation and angiogenesis should be evaluated as targets for prevention and/or therapy in ileal carcinoids.…”

Section: Profiling Of Susceptibility Genes For Ileal Carcinoidsmentioning

confidence: 99%

Profiling of Ileal Carcinoids

Nilsson

2012

Neuroendocrinology

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Identification of common molecular mechanisms is needed to facilitate the development of new treatment options for patients with ileal carcinoids. Purpose of Review: Recent profiling studies on ileal carcinoids were examined to obtain a comprehensive view of risk factors, genetic aberrations, and transcriptional alterations. Special attention was paid to mechanisms that could provide novel targets for therapy. Results: Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) at IL12A and DAD1 are associated with an increased risk of ileal carcinoids. Genomic profiling revealed distinct patterns of copy-number alterations in ileal carcinoids. Two groups of carcinoids could be identified by hierarchical clustering. A major group of tumors was characterized by loss on chromosome 18 followed by additional losses on chromosomes 3p, 11q, and 13. Three minimal common regions of deletions were identified at 18q21.1–q21.31, 18q22.1–q22.2, and 18q22.3–q23. A minor group of tumors was characterized by clustered gains on chromosomes 4, 5, 7, 14, and 20. Expression profiling identified three groups of ileal carcinoids by principal component analysis. Tumor progression was associated with changes in gene expression including downregulation of MIR133A. Candidate genes for targeted therapy included ERBB2/HER2, DAD1, PRKCA, RYBP, CASP1, CASP4, CASP5, VMAT1, RET, APLP1, OR51E1, GPR112, SPOCK1, RUNX1, and MIR133A.Conclusion: Profiling of ileal carcinoids has revealed recurrent genetic alterations and distinct patterns of gene expression. Frequent alterations in cellular pathways and genes were identified, suggesting novel targets for therapy. Translational studies are needed to validate suggested molecular targets.

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“…Because of the functional relevance of IL12, several molecular epidemiologic studies have been done to investigate the association between the IL12A and IL12B polymorphisms and risk of cancers, including nonHodgkin lymphoma (22 -24), hepatocellular carcinoma (25), lung cancer (26), gastric cancer (27,28), and others (29 -32). In the present study, we hypothesized that IL12A and IL12B polymorphisms were associated with cervical cancer risk.…”

mentioning

confidence: 99%

Interactions of IL-12A and IL-12B Polymorphisms on the Risk of Cervical Cancer in Chinese Women

Chen

Han

Wang

et al. 2008

Clinical Cancer Research

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Purpose: Accumulative evidence suggests that interleukin-12 (IL-12) plays a central role in the Th1 responses and thus participates in the carcinogenesis of human papillomavirus^related cervical cancer. We hypothesized that potentially functional polymorphisms in IL12A and IL12B may individually and jointly contribute to cervical cancer risk. Experimental Design: We genotyped IL12A rs568408 [3 ¶ untranslated region (UTR) G>A] and rs2243115 (5 ¶UTR T>G) and IL12B rs3212227 (3 ¶UTR A>C) in a hospital-based study of 404 cervical cancer cases and 404 cancer-free controls. Results: The IL12A rs568408 GA/AA and IL12B rs3212227 AC/CC variant genotypes were associated with a significantly increased risk of cervical cancer [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.06-1.93; and adjusted odds ratio, 1.30; 95% CI, 0.97-1.75, respectively], compared with their corresponding wild-type homozygotes. Moreover, a significant gene-gene interaction of these 2 loci were evident in the risk of cervical cancer, and subjects carrying variant genotypes of both loci had a1.82-fold (95% CI, 1.28-2.57) increased risk of cervical cancer. In the stratified analyses, the combined genetic effect was more pronounced in patients who had earlystage tumors or more parities. Subjects carrying rs568408 AG/AA and rs3212227 AC/CC genotypes and having >2 parities showed a 6.00-fold (95% CI, 2.86-12.56) elevated cervical cancer risk (P for multiplicative interaction = 0.046). Conclusion:These findings suggest that IL12A rs568408 and IL12B rs3212227 may individually and jointly contribute to the risk of cervical cancer and may modify cervical cancer risk associated with parity, but these data need further validation.

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Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals

Cited by 38 publications

References 40 publications

Emerging role of IL-23/IL-17 axis inH pylori-associated pathology

Emerging role of IL-23/IL-17 axis inH pylori-associated pathology

Profiling of Ileal Carcinoids

Interactions of IL-12A and IL-12B Polymorphisms on the Risk of Cervical Cancer in Chinese Women

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