Effects of eNOS gene polymorphisms on individual susceptibility to cancer: A meta-analysis

Jiang, Nan; Liu, Yaqing; Xu, Chunjin; Ge, Dahe

doi:10.1016/j.niox.2018.12.006

Cited by 8 publications

(7 citation statements)

References 62 publications

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“…The findings regarding the involvement of eNOS polymorphism in cancer are controversial, likely due to considered factors such as analyzed sample size, cancer type, and the ethnic-dependent variation 41 . A meta-analysis study reported a significant association of eNOS intron 4, and -786T>C polymorphism in overall cancer and 894 G>T polymorphisms with the risk of breast cancer 42 .…”

Section: Discussionmentioning

confidence: 99%

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

Housein

Kareem

Salihi

2021

Sci Rep

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This study was carried out to assess the impact of nickel nanoparticles (NiNPs) as well as scorpion venom on colorectal cancer (CRC) cells in the presence and/or absence of 5-fluorouracil (5-FU), hydrogen sulfide (H2S), and nitric oxide (NO) donors and to determine alterations in endothelial NO synthase (eNOS) and cystathionine γ-lyase (CSE) enzyme-producing genes in CRC patients. The IC50 of both H2S and NO donors, along with NiNPs, were determined. The CRC cells were treated for 24hrs, and the cytotoxic activities were assessed using the MTT test. Moreover, the apoptosis was determined after 24hrs and 48hrs using TUNEL assay. Furthermore, the mutations in the eNOS gene (intron 4, -786T>C and 894 G>T) and CSE gene (1364GT) were determined using direct sequencing. The IC50 values for sodium disulfide (Na2S) and sodium nitroprusside (SNP) at 24hrs treatment were found to be 5 mM and 10−6 M, respectively, while the IC50 value for 5-FU was reached after 5-days of treatment in CRC cell line. Both black and yellow scorpion venoms showed no inhibition of cell proliferation after 24hrs treatment. Furthermore, Na2S showed a significant decrease in cell proliferation and an increase in apoptosis. Moreover, a co-treatment of SNP and 5-FU resulted in inhibition of the cytotoxic effect of 5-FU, while a combination treatment of NiNPs with Na2S, SNP, and 5-FU caused highly significant cytotoxicity. Direct sequencing reveals new mutations, mainly intronic variation in eNOS gene that has not previously been described in the database. These findings indicate that H2S promotes the anticancer efficiency of 5-FU in the presence of NiNPs while NO has antiapoptotic activity in CRC cell lines.

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Section: Discussionmentioning

confidence: 99%

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

Housein

Kareem

Salihi

2021

Sci Rep

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“…The results of the present study show that eNOS −786 T/C functional polymorphism located in the promoter region of the eNOS gene confers a 3.6-fold increase of OSCC risk on CC homozygotes. Previous investigations have correlated this SNP with an overall elevated risk of cancer [21][22][23], including, in particular, gastric [24], colorectal [25], and prostate [26] cancers. Interestingly, a meta-analysis from 2010 showed that this genetic variant could reduce the risk of breast cancer [27].…”

Section: Discussionmentioning

confidence: 99%

“…Yao et al, in contrast, suggested that 894 G/T could even reduce breast cancer risk [27]. Some studies, however, have associated 894 G/T with individual susceptibility for cancer [23]. Other research also linked this SNP to colorectal [25] and prostate cancers [26] as well as to the risk of developing large tumors in patients with urothelial cancer [9].…”

Section: Discussionmentioning

confidence: 99%

Endothelial nitric oxide synthase polymorphisms/haplotypes are strong modulators of oral cancer risk in Serbian population

et al. 2020

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Oral carcinoma is the sixth most common malignancy worldwide, with survival rates of approximately 50%. The major type of oral cancer, present in 90% of the cases, is oral squamous cell carcinoma (OSCC). The genetic background predisposing an individual to OSCC is complex and largely unknown. Studies have suggested that endothelial nitric oxide synthase (eNOS) gene polymorphisms modulate the cancer risk, prompting us to assess the impact of three functional eNOS gene polymorphisms on OSCC risk. The present study included 50 patients with OSCC and 110 controls. Polymerase chain reaction and restriction fragment length polymorphism analysis were used for genotyping of single-nucleotide polymorphisms −786 T/C (rs2070744) and 894 G/T (rs1799983) and variable number of tandem repeats (VNTR) intron 4b/a polymorphism. Homozygous carriers of −786 T/C and intron 4b/a VNTR variant alleles paired with a significant increase of oral cancer risk [odds ratio (OR): 3.63, 95% confidence interval (CI): 1.08-12.21; P = 0.045 and OR: 11.29, 95% CI: 2.71-47.11; P < 0.001, respectively]. When combined, CC and 4b4a genotypes together led to a 21-fold OSCC risk increase (OR: 21, 95% CI: 2.07-213.29; P = 0.006). Haplotype analysis showed that the C-G-4b haplotype conferred an 11-fold increase in OSCC risk. In conclusion, eNOS polymorphisms considerably influence levels of OSCC risk in the Serbian population. Keywords; eNOS, gene polymorphisms, haplotype, oral cancer Statistical analysis All statistical calculations were completed using the SPSS Statistics for

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“…This variant is linked to a substantial reduction in eNOS enzyme activity. Notably, this SNP exhibited associations with PCa, BLCA, and BC [33,36,[38][39][40]45]. Concerning BC development, the effect of the T allele (minor allele) depends on the menopause status, exerting a protective effect on postmenopausal women [48].…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

“…To date, many meta-analyses associated rs2070744 with the risk of overall cancer, particularly among individuals of Caucasian descent. Further clustering by cancer type links the C allele (the minor and also ancestral allele) to a higher risk of breast (BC), prostate (PCa), and bladder (BLCA) cancers [33,[36][37][38][39][40][41]. In a study regarding oral squamous cell carcinoma (OSCC), individuals with the TC genotype faced an increased likelihood of progressing to an advanced clinical stage (III/IV) compared to those with the TT genotype [42].…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Contribution of Endothelial Dysfunction to Cancer Susceptibility and Progression: A Comprehensive Narrative Review on the Genetic Risk Component

de Melo,

Tavares,

Pereira

et al. 2024

CIMB

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Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS, EDN1, ACE, AGT, F2, SELP, SELE, VWF, ICAM1, and VCAM1, was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases.

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Effects of eNOS gene polymorphisms on individual susceptibility to cancer: A meta-analysis

Cited by 8 publications

References 62 publications

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

Endothelial nitric oxide synthase polymorphisms/haplotypes are strong modulators of oral cancer risk in Serbian population

Contribution of Endothelial Dysfunction to Cancer Susceptibility and Progression: A Comprehensive Narrative Review on the Genetic Risk Component

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