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Association of VEGF Gene Polymorphisms with the Risk and Prognosis of Cutaneous Squamous Cell Carcinoma.

ABSTRACT: BACKGROUND Cutaneous squamous cell carcinoma (cSCC) is the second most common type of non-melanoma skin cancer (NMSC) globally. The aims of this study were to further systematically clarify the potential association of rs833061 (-460 C>T) and rs1570360 (-1154 G>A), two SNPs of VEGF, with the risk of cSCC and the prognostic impacts on cSCC patients. MATERIAL AND METHODS This hospital-based case-control study analyzed peripheral venous blood collected from 100 cSCC patients and 124 healthy controls, and gathered personal information on patients. Genotypes of the VEGF gene -460C>T and -1154G>A polymorphism were detected using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Different distributions of allele frequencies and genotype in the case and control group were measured, comparing different genotype differences in the survival of patients with cSCC. RESULTS Distributions of allele frequencies and genotype of -460 C>T in the case and control group were statistically different; the TT + CT genotype was significantly correlated with a decrease risk of cSCC (OR=0.36, 95% CI=0.21-0.63, P<0.001). There was no difference in the distribution of allele frequencies and genotype of -1154 G>A between control and case groups. For -1154460C>T, the CC genotype was an adverse factor, associated with a significant decrease in the survival status of cSCC patients (P<0.001). For VEGF-1154 G>A, the AA genotype was significantly correlated with the reduced overall survival in cSCC patients, with the mean survival time of 23.88 months (P=0.009). CONCLUSIONS The VEGF gene -460 C>T polymorphism and -1154 G>A polymorphism may serve as potential genetic markers for the risk and prognosis of cSCC.

SUBMITTER: Nie XJ

PROVIDER: S-EPMC5074797 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Association of VEGF Gene Polymorphisms with the Risk and Prognosis of Cutaneous Squamous Cell Carcinoma.

Nie Xiao-Juan XJ Liu Wen-Min WM Zhang Li L

Medical science monitor : international medical journal of experimental and clinical research 20161012

BACKGROUND Cutaneous squamous cell carcinoma (cSCC) is the second most common type of non-melanoma skin cancer (NMSC) globally. The aims of this study were to further systematically clarify the potential association of rs833061 (-460 C>T) and rs1570360 (-1154 G>A), two SNPs of VEGF, with the risk of cSCC and the prognostic impacts on cSCC patients. MATERIAL AND METHODS This hospital-based case-control study analyzed peripheral venous blood collected from 100 cSCC patients and 124 healthy control ...[more]

PMID: 27729640

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Project description:BACKGROUND:Tumour necrosis factor-alpha (TNF-?) and nuclear factor of kappa light chain gene enhancer in activated B cells (NF-?B) play critical role in carcinogenesis processes like tumour initiation, proliferation, migration and invasion. Single nucleotide polymorphisms in TNF-?, NF-?B and its inhibitor I?B genes were shown to be associated with susceptibility and prognosis of several cancers; however, their role in esophageal squamous cell carcinoma (ESCC) is not well recognised. Therefore, in present study, we aimed to investigate association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of ESCC in northern Indian population. METHODS:We genotyped 290 ESCC patients (including 162 followed up cases) and 311 mean age, gender and ethnicity matched controls for TNFA -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3'UTRA>G) polymorphisms using PCR alone or followed by RFLP and TaqMan assay. RESULTS:TNFA-308GA genotype was associated with increased risk of ESCC specifically in females and in patients with regional lymph node involvement, while, NFKBIA -826CT+TT genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3'UTRA>G polymorphisms, C-826G3'UTR and T-826A3'UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3'UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to '0' risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients. CONCLUSION:TNFA-308 and NFKBIA (-826C>T and 3'UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.

Project description:Importance:No study, to our knowledge, has prospectively investigated a dose-response association between lifetime indoor tanning and risk of cutaneous squamous cell carcinoma (SCC). Objective:To investigate the dose-response association between lifetime indoor tanning and SCC risk, the association between duration of use and age at initiation with SCC risk, and the association between age at initiation and age at diagnosis. Design, Setting, and Participants:This cohort study included data from women born from 1927 to 1963 from the Norwegian Women and Cancer study, established in 1991 with follow-up through December 31, 2015. Baseline questionnaires were issued to participants from 1991 to 2007, with follow-up questionnaires given every 5 to 7 years. Data analysis was performed from January 2, 2018, to March 2, 2019. Exposures:Participants reported pigmentation factors. Sunburns, sunbathing vacations, and indoor tanning were reported for childhood, adolescence, and adulthood. Main Outcomes and Measures:Information on all cancer diagnoses and dates of emigration or death were obtained through linkage to the Cancer Registry of Norway, using the unique personal identification number of Norwegian citizens. Results:A total of 159?419 women (mean [SD] age at inclusion, 49.9 [8.3] years) were included in the study. During follow-up (mean [SD], 16.5 [6.4] years), 597 women were diagnosed with SCC. Risk of SCC increased with increasing cumulative number of indoor tanning sessions. The adjusted hazard ratio (HR) for highest use vs never use was 1.83 (95% CI, 1.38-2.42; P?<?.001 for trend). A significantly higher risk of SCC was found among women with 10 years or less of use (HR, 1.41; 95% CI, 1.08-1.85) and more than 10 years of use (HR,?1.43; 95% CI, 1.16-1.76) and among women with age at initiation of 30 years or older (HR,?1.36; 95% CI, 1.11-1.67) and younger than 30 years (HR,?1.51; 95% CI, 1.18-1.92) vs never users. No significant association was found between age at initiation and age at diagnosis (estimated regression coefficient, -0.09 [95% CI, -1.11 to 0.94] for age at initiation of ?30 years and -0.02 [95% CI, -1.27 to 1.22] for <30 years vs never use). Conclusion and Relevance:The findings provide supporting evidence that there is a dose-response association between indoor tanning and SCC risk among women. The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation. These results support development of policies that regulate indoor tanning.

Project description:ImportanceRetinoids are bioactive forms of vitamin A that are essential in the maintenance of epithelial maturation and differentiation. Synthetic retinoids are used in chemoprevention of skin cancer among high-risk populations with potential adverse effects. Epidemiologic data on vitamin A intake and risk of cutaneous squamous cell carcinoma (SCC) are limited.ObjectiveTo examine whether vitamin A intake is associated with a reduction in SCC risk.Design, settings, and participantsThis cohort study prospectively examined intake of vitamin A and carotenoids and SCC risk in the Nurses' Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Diet was assessed repeatedly. Incident SCC was confirmed by pathologic reports. Data analysis was performed from June 21, 2017, to December 4, 2018.ExposuresIntakes of vitamin A, retinol, and carotenoids.Main outcomes and measuresIncident SCC. Cox proportional hazards regression models were used to compute cohort-specific hazard ratios (HRs) and 95% CIs. Pooled HRs of the cohort-specific results were calculated.ResultsA total of 3978 SCC cases in 75 170 women in the Nurses' Health Study (mean [SD] age, 50.4 [7.2] years) and 48 400 men in the Health Professionals Follow-up Study (mean [SD] age, 54.3 [9.9] years) were documented. Higher total vitamin A was associated with a reduction in SCC risk; with quintile 1 as the reference, the pooled multivariate HRs for the increasing quintiles of vitamin A intake were 0.97 (95% CI, 0.87-1.07) for quintile 2, 0.97 (95% CI, 0.80-1.17) for quintile 3, 0.93 (95% CI, 0.84-1.03) for quintile 4, and 0.83 (95% CI, 0.75-0.93) for quintile 5 (P < .001 for trend). Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk; the pooled HRs for the highest quintiles of intake compared with the lowest quintiles were 0.88 (95% CI, 0.79-0.97; P = .001 for trend) for total retinol, 0.86 (95% CI, 0.76-0.96; P = .001 for trend) for beta cryptoxanthin, 0.87 (95% CI, 0.78-0.96; P < .001 for trend) for lycopene, and 0.89 (95% CI, 0.81-0.99; P = .02 for trend) for lutein and zeaxanthin. The results were generally consistent by sex and other SCC risk factors.Conclusions and relevanceThis study suggests that increased intake of dietary vitamin A is associated with decreased risk of incident SCC. Future studies are needed to determine whether vitamin A supplementation has a role in chemoprevention of SCC.

Dataset Information

Association of VEGF Gene Polymorphisms with the Risk and Prognosis of Cutaneous Squamous Cell Carcinoma.

Publications

Association of VEGF Gene Polymorphisms with the Risk and Prognosis of Cutaneous Squamous Cell Carcinoma.

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