Association between STAT3 polymorphisms and cancer risk: a meta-analysis

Yan, Rong; Lin, Fang; Hu, Chao; Tong, Shilun

doi:10.1007/s00438-015-1074-y

Cited by 11 publications

(14 citation statements)

References 34 publications

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“…Though the evidence has been mixed 16–21 , IL-6 SNPs have been shown to correlate with serum and intratumoral IL-6 levels 22–24 , as well as the susceptibility 16–19,21,23,25 and survival 20 of multiple cancers, including CRC. Similarly, STAT3 common genetic variants have been associated with cancer risk 26 . However, the potential of IL-6/STAT3 SNPs to predict efficacy of anti-angiogenic therapy in CRC has not been tested.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy

Matsusaka

Hanna

Cao

et al. 2016

Clinical Cancer Research

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Background The IL-6/STAT3 axis promotes inflammation, angiogenesis, and cancer. The effect of genetic variants within this pathway on benefit from anti-angiogenic cancer therapy is unknown. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in IL-6/STAT3 signaling can predict efficacy of bevacizumab-based chemotherapy in metastatic colorectal cancer (mCRC) patients Methods Associations between potentially functional IL-6 (rs2069837, rs1800795) and STAT3 (rs744166, rs4796793) SNPs and clinical outcomes (progression-free survival, overall survival and tumor response rate) were evaluated in mCRC patients receiving first-line FOLFIRI plus bevacizumab in two randomized phase III trials: TRIBE (n=223, training cohort) and FIRE-3 (n=288, validation cohort). Patients receiving FOLFIRI plus cetuximab in FIRE-3 (n=264) served as a control cohort. The interaction between genotype and primary tumor location with clinical outcomes was examined. Genomic DNA isolated from whole blood or tumor tissue was analyzed by PCR-based direct sequencing. Results Patients with an IL-6 rs2069837 G allele treated with FOLFIRI plus bevacizumab had an inferior PFS than those with the A/A genotype in TRIBE (9.4 v. 11.1 months, HR=1.53, 95% CI 1.12, 2.10, P=0.004) and FIRE-3 (8.8 v. 10.9 months, HR=1.40, 95% CI 1.06, 1.85, P=0.015). These associations were confirmed in multivariable analyses, and were not seen in the control cohort. In subgroup analysis, the effect of IL-6 rs2069837 on PFS was present only in patients with left-sided cancers, but the test for interaction was not significant. Conclusion IL-6 rs2069837 genotype is a clinically relevant prognostic factor in mCRC patients treated with first-line bevacizumab-based chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy

Matsusaka

Hanna

Cao

et al. 2016

Clinical Cancer Research

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“…STAT3 gene is located on chromosome 17q21. It has been hypothesized, that SNPs in STAT3 gene may influence STAT3 expression, activation upon stimulation and contribute to predisposition to inflammatory and neoplastic diseases [45].…”

Section: Discussionmentioning

confidence: 99%

“…In the present study we examined two STAT3 polymorphisms: rs4796793 (in the promoter) and rs2293152 (in intron 11). Both SNPs were previously investigated in the context of several neoplasia, but the results were inconsistent [45]. For instance, rs4796793 polymorphism was related to parametrial invasion and poor differentiation of cervical cancer [41] and increased risk of breast cancer [52].…”

Section: Discussionmentioning

confidence: 99%

“…Histopathological diagnoses were made based on the assessment of the hematoxylin and eosin stained sections, according to the classification system of the World Health Organization (WHO) [27]. Single nucleotide polymorphisms (SNPs) were chosen based on their previously documented significance in other neoplasia, on their functional relevance, as well as on the minor allele frequency (MAF) ≥ 0.1 in the Caucasian population (https://www.ncbi.nlm.nih.gov/snp/) [13, 14, 16, 17, 21, 26, 41, 44, 45, 49–51].…”

Section: Methodsmentioning

confidence: 99%

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STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

et al. 2019

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Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6, which is the upstream element of IL-6/JAK/STAT3 pathway. The correlation between polymorphisms of the genes related to this pathway and cancer risk/prognosis have been previously investigated in several neoplasia, but available data concerning BCC are scarce. In the present study, rs1800795 (-174 G/C) IL-6 gene polymorphism and two polymorphisms in the STAT3 gene, namely rs2293152 (intron 11, C/G) and rs4796793 (-1697, C/G) were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated patients with BCC and of mean age 70.39 ± 11.43 (69.83 ± 12.32 women, 71.03 ± 10.31 men) and 198 healthy, unrelated age- and sex-matched volunteers. IL-6 and STAT3 polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). Serum concentration of IL-6 was measured using the ELISA test. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR 1.86; 95% CI 1.22–2.84; p = 0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.94; 95% CI 1.59–9.77; p = 0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR = 0.24; 95% CI 0.12–0.49; p < 0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR 1.31; 95% CI 1.01–1.69; p = 0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.66; 95% CI 1.33–10.10; p = 0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR 1.59; 95% CI 1.01–2.49; p = 0.04). IL-6 serum level positively correlated with the tumor size.

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“…The analysis of polymorphisms within the STAT3 gene may reveal correlations with some biochemical and laboratory parameters. For our analysis we chose three STAT3 SNPs (rs1053005 located in the 3′UTR region and rs1026916 and rs2293152 both located in an intronic region), knowing that previously a significant association of these STAT3 SNPs was found with other Th17 cell dependent autoimmune diseases such as both clinical phenotypes of IBD [ 15 ], autoimmune thyroid diseases [ 25 ], AS [ 16 ], obesity [ 17 ] and cancers [ 18 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Lack of significant association between selected STAT3 polymorphisms and rheumatoid arthritis in the Polish population

et al. 2018

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ObjectivesRheumatoid arthritis (RA) is the most common systemic inflammatory disease and is of unknown etiology. The altered balance between immunosuppressive and inflammatory T cell subpopulations exerts a huge impact on RA pathogenesis. The STAT3 protein regulates genes involved in the immune responses. It regulates maturation of T and B cells. Its abnormal activity is significantly associated with autoimmune diseases and cancer development. We aimed to evaluate the contribution of three potentially functional single nucleotide polymorphisms (SNPs) within the STAT3 gene to susceptibility and severity of RA in the Polish population.Material and methodsA total of 595 patients with RA and 330 healthy individuals were included in the study. DNA from patients and healthy subjects was obtained from peripheral blood using standard DNA isolating methods. The STAT3 rs1053005, rs1026916 and rs2293152 polymorphisms were genotyped using the TaqMan SNP genotyping assay. The accuracy of SNP genotyping was confirmed using direct DNA sequence analysis.ResultsThe distribution of STAT3 polymorphisms did not differ significantly between cases and controls. Our results revealed a tendency only, where rs1026916 AA genotype occurred more frequently in RA patients compared to healthy controls, in codominant (p = 0.09), dominant (p = 0.06) and recessive (p = 0.09) models. STAT3 rs2293152 polymorphism was associated with higher DAS28 (p = 0.014 codominant model; p = 0.003 dominant model), increased number of swollen joints (p = 0.02), higher VAS (p = 0.01) and higher HAQ score (p = 0.05).ConclusionsWe did not observe a significant association between the three studied STAT3 genetic variants and increased susceptibility to or severity of RA. Only the STAT3 rs2293152 polymorphism was associated with parameters that indicate a more severe course of the disease. However, its distribution did not differ between RA and control groups. According to our observations these 3 studied STAT3 SNPs may not be used as risk factors for developing RA.

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Association between STAT3 polymorphisms and cancer risk: a meta-analysis

Cited by 11 publications

References 34 publications

Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy

Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy

STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

Lack of significant association between selected STAT3 polymorphisms and rheumatoid arthritis in the Polish population

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