Polymorphisms in the Genes Related to Angiogenesis Are Associated With Uterine Cervical Cancer

Ramos-Flores, Christian; Romero-Gutiérrez, Teresa; Delgado‐Enciso, Iván; Maldonado, Gabriela Enríquez; Plascencia, Víctor Montaño; Vázquez‐Vuelvas, Oscar F.; Quintero‐Ramos, Antonio; Mejía, Roberto Chaparro; Espinoza-Gomez, Francisco; Baltazar-Rodríguez, Luz M.; Valdez-Velázquez, Laura Leticia

doi:10.1097/igc.0b013e31829f4c6f

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…In gene-environment interaction, carriers of TGFB1 -509TT genotype with tobacco usage were at higher risk of CC (OR = 3.67, 95 % CI = 0.38–35.1) [ 41 ]. The association found in this study is according to previous report where TGF-beta family members play a key role in cellular growth, proliferation, differentiation and angiogenesis of several cancer types [ 42 ] and a marginal protection for early stage 1B but risk for stage II of CC of TGFB1 -509 T allele has been reported [ 41 ].…”

Section: Discussionsupporting

confidence: 87%

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Torres-Poveda¹,

Burguete-García²,

Bahena-Román³

et al. 2016

BMC Cancer

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BackgroundAlterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age.MethodsPeripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA.ResultsAfter analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP (−590C > T IL-4), C of SNP (−573G > C IL-6), A of SNP (−592C > A IL-10), T of SNP (−819C > T IL-10) and T of SNP (−509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475–2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208–2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332–2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192–2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354–2.701, p = 0.0001), respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases.ConclusionThe significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of susceptibility to this disease.

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Section: Discussionsupporting

confidence: 87%

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Torres-Poveda¹,

Burguete-García²,

Bahena-Román³

et al. 2016

BMC Cancer

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“…Progression of tumour in vivo can be taken from the fact that TGFb1 secreted by the tumour may lead to suppression of immune response and to an enhancement of angiogenesis in the tumour environment [55]. The polymorphisms in the genes related to angiogenesis -PAI-1 (675 4G/5G) and TGFb1 (G-800A), segregated solely or combined, might contribute to the increased susceptibility to uterine cervical cancer [118].…”

Section: Prace Poglądowementioning

confidence: 99%

Transforming growth factor beta1 (TGFbeta1) in physiology and pathology

Kajdaniuk¹,

Marek²,

Borgiel−Marek³

et al. 2013

Endokrynologia Polska

166

118

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This review describes precisely the consequence of TGFb1 prevalence in the organism, and its significant influence on physiological and pathophysiological processes. Organ and tissue distinctiveness hinder unambiguous characterisation of the cytokine. However, there are constant functions of TGFb1 inducing no controversy: it participates in foetal development, control of cell growth and differentiation, induces fibrosis and scar formation (the process of 'wound healing'), causes the suppression of immune response, is involved in angiogenesis, the development of tumours, and inflammatory processes. Thus, TGFb1 is a multifunctional cytokine. There are three fundamental directions of its activities: I. TGFb1 regulates cell proliferation, growth, differentiation and cells movement. II. TGFb1 has immunomodulatory effects. III. TGFb1 has profibrogenic effects. TGFb1 action can be local and systemic. This review describes TGFb1 in pathology: colitis ulcerosa, Crohn's disease, coeliac disease, diabetic nephropathy, diabetic retinopathy and diabetic foot, pulmonary hypertension, and Alzheimer's disease. TGFb1 and its receptors are also of interest to endocrinologists. Lack of TGFb1-dependent growth control may result in oncogenesis: papillary, follicular and anaplastic thyroid cancers, prostate, breast and uterine cervical cancer, oesophagus, gastric, colorectal and liver cancers, NSCLC, and malignant melanoma. Excessive TGFb1 activity is an integral part of the fibrotic processes occurring in the response to injury. An increased TGFb1 expression has been observed in patients with pulmonary, kidney, and liver fibrosis. In chronic hepatitis, the prolonged stimulation of hepatic stellate cells being the result of chronic damage to hepatocytes results in the release of profibrogenic abundant factors such as TGFb1 and leads to the development of liver cirrhosis. The results of experimental procedures and treatment known as anti-TGFb1 strategy acting against the fibrosis in various tissues leads to hope regarding the use of anti-TGFb1 strategy in clinical practice. StreszczenieW artykule poglądowym szczegółowo opisano konsekwencje rozpowszechnienia TGFb1 w organizmie oraz jego wpływ na szereg procesów fizjologicznych i patofizjologicznych. Istotne odrębności narządowe i tkankowe utrudniają jednoznaczną charakterystykę tej cytokiny. Istnieją jednak stałe funkcje TGFb1 nie wzbudzające kontrowersji: uczestniczy w rozwoju płodu, regulacji wzrostu i różnicowa-nia komórek, indukuje proces włóknienia i bliznowacenia (proces "gojenia rany"), powoduje hamowanie odpowiedzi immunologicznej, uczestniczy w angiogenezie, w rozwoju nowotworów, w procesach zapalnych -jest więc cytokiną wieloczynnościową. Można wyróżnić trzy fundamentalne kierunki jego działania: I -TGFb1 reguluje proliferację, wzrost, różnicowanie i przemieszczanie komórek; II -TGFb1 wykazuje działanie immunomodulujące; III -TGFb1 wykazuje działanie profibrogenne. Działanie TGFb1 może mieć charakter miejscowy i systemowy. Opisano udział TGFb1 w stanach patologicznyc...

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“…Furthermore, the rs1799889 polymorphism was found to have higher risks for breast, endometrial and colorectal cancer, but there was no effect on susceptibility to uterine cervical cancer. 19,22,31,34 However, the linkage disequilibrium analysis detected that both 4G for PAI-1 rs1799889 and A for TGF-β1 rs1800468 pair-haplotype was in strong linkage disequilibrium with a statistically increased risk to uterine cervical cancer. 34 Meanwhile, the linkage disequilibrium analysis detected that both 4G4G for PAI-1 rs1799889 and CC for uPArs 4065 pair-haplotype was in strong linkage disequilibrium with a statistically increased risk to cervical neoplasia.…”

Section: Discussionmentioning

confidence: 97%

PAI-1 Polymorphisms Have Significant Associations With Cancer Risk, Especially Feminine Cancer

Peng

Guo

Li³

2021

Technol Cancer Res Treat

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Background: The plasminogen activator inhibitor-1 (PAI-1) was found in many types of tumor cells, which involved in tumorigenesis. Some studies investigated the associations between PAI-1 polymorphisms and various cancers, but the results were inconsistent. So this study did a meta-analysis to assess the strength of relationship between PAI-1 and cancer. Methods: Articles that meet the requirements were searched from PubMed, EMBASE, MEDLINE, Scopus, CNKI, Wanfang and SinoMed electronic databases before June 17th 2021. Stata version 11.2 was performed to merge the odds ratios (ORs) values and calculate 95% confidence intervals (CIs). Stratified analyses were assessed on the basis of types of cancer, ethnicity and source of the control group. Heterogeneity and sensitivity analysis were tested, and publication bias was also estimated. A meta-regression analysis was applied to explore sources of heterogeneity. The false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) test were used to assess the credibility of statistically significant associations. Results: Ultimately, in this study, 33 eligible reports were included with 9550 cases and 10431 controls for the rs1799889 polymorphism, 5 reports with 2705 cases and 3168 controls for the rs2227631 polymorphism, and 4 reports with 2799 cases and 4011 controls for the rs2227667 polymorphism. The ORs and 95% CIs showed a statistically significant relationship between rs1799889 4G>5G polymorphism and cancer risk, especially in feminine cancer. The term refers to cancers that occur in the female reproductive system, such as ovarian, breast, endometrial and cervical cancer. Moreover, there was no association observed for the PAI-1 promoter A>G polymorphism (rs2227631 and rs2227667). In further subgroup analyses of 4G>5G polymorphism (rs1799889), an increased susceptibility to cancer was observed in Caucasians group and some types of cancer groups. Conclusions: This article comes to a conclusion that the rs1799889 polymorphism might help to increase the risk of cancer; moreover, the susceptibility to feminine cancer is more evident.

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Polymorphisms in the Genes Related to Angiogenesis Are Associated With Uterine Cervical Cancer

Abstract: The polymorphisms in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-β1, segregated solely or combined, might contribute to the increased susceptibility to UCC in a Mexican population.

Cited by 8 publications

References 26 publications

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Transforming growth factor beta1 (TGFbeta1) in physiology and pathology

PAI-1 Polymorphisms Have Significant Associations With Cancer Risk, Especially Feminine Cancer

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