The role of endothelial nitric oxide synthase gene polymorphisms in patients with lung cancer

Our plain-English summary of The role of endothelial nitric oxide synthase gene polymorphisms in patients with lung cancer, by C. Koçer, N. Benlier, S.O. Balci, et al (The Clinical Respiratory Journal, 2020).

The study

• Authors: C. Koçer, N. Benlier, S.O. Balci, S. Pehlivan, M. Şanli, M. Nacak
• Journal: The Clinical Respiratory Journal
• Published: 2020;14(10):948-955
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Lung cancer is a disease characterized by uncontrolled cell growth in the lung tissues. The most common causes of lung cancer include smoking, exposure to radon gas, asbestos, environmental pollutants as well as genetic factors. Nitric oxide (NO) has potential mutagenic and carcinogenic activity and may play an important role in lung cancer. Endothelial NO, synthesized from L-arginine by endothelial NO synthase (eNOS), inhibits apoptosis and promotes angiogenesis and tumor cell proliferation. The aim of the present study was to examine the possible relationship between eNOS gene intron 4 variable number of tandem repeat (VNTR) and exon 7-G894T (Glu298Asp) polymorphisms and lung cancer risk.

Methods: DNA was extracted from peripheral blood leukocytes of 107 lung cancer patients and 100 control subjects. Designated polymorphisms were identified by polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP).

Results: Our study showed that the frequencies of the b/b genotype and b allele of eNOS gene intron 4 VNTR polymorphism were significantly higher in lung cancer patients than in controls (P < 0.05). However, there was no significant association between eNOS gene G894T polymorphism and lung cancer risk (P > 0.05).

Conclusion: These results suggest that the presence of the intron 4 VNTR* b allele and b/b genotype may be a genetic risk factor for development of lung cancer. Further larger-scale studies are needed to confirm these findings.

© 2020 John Wiley & Sons Ltd.

In plain English

This was a case-control genetic study from Turkey. It did not measure asbestos exposure, which the article mentions only as one known cause of lung cancer. The authors took DNA from the blood of 107 lung cancer patients diagnosed at a Gaziantep University thoracic surgery clinic between May 2009 and May 2010, and of 100 healthy volunteers. They tested two variants of the endothelial nitric oxide synthase (eNOS) gene. For the G894T (Glu298Asp) variant, patients and controls did not differ significantly. For the intron 4 repeat variant, the b/b genotype was found in 83.2% of patients and 72.0% of controls (p=0.0386). The b allele was also more frequent in patients (0.911 versus 0.845; p=0.0275). This difference was significant in patients with epidermoid (squamous cell) carcinoma but not in those with adenocarcinoma or small cell lung cancer. Patients were older and more often smokers than controls. The authors concluded that the b/b genotype and b allele may be a genetic risk factor, especially for epidermoid carcinoma. They named their small sample size and their inability to measure serum nitric oxide as limitations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case-control genetic association study comparing gene variant frequencies in lung cancer patients and healthy controls
• Who was studied: 107 lung cancer patients (10 female, 97 male) diagnosed at the Thoracic Surgery outpatient clinic of Gaziantep University Faculty of Medicine, Turkey, between 22.05.2009 and 22.05.2010, plus 100 healthy, unrelated control volunteers (38 female, 62 male) from the same clinic
• Exposure: No environmental or occupational exposure was studied. The 'exposure' was carrying variants of the eNOS gene: the intron 4 27 bp repeat (VNTR, a and b alleles) and the exon 7 G894T (Glu298Asp) variant. Asbestos appears only in the introduction as a known cause of lung cancer and was not assessed.
• Main results:
  • eNOS G894T variant: genotypes GG, GT and TT were 69.2%, 29.9% and 0.9% in lung cancer patients and 65.0%, 34.0% and 1.0% in controls. Genotype and allele differences were not statistically significant (p>0.05).
  • Intron 4 repeat variant: the b/b genotype was found in 83.2% of all lung cancer patients (89 of 107) and 72.0% of controls (72 of 100). Odds ratio 1.9 (95% CI 0.99-3.75), p=0.0386.
  • The b allele frequency was 0.911 in lung cancer patients and 0.845 in controls. Odds ratio 1.9 (95% CI 1.03-3.46), p=0.0275.
  • Among the 51 patients with epidermoid lung carcinoma, Table 4 gives b/b genotype 86.3% versus 72.0% in controls (odds ratio 2.4, 95% CI 0.98-6.07, p=0.0362). It gives the b allele as 93.1% versus 84.5% (odds ratio 2.5, 95% CI 1.06-5.87, p=0.0219).
  • No significant difference was found for the intron 4 variant in the lung adenocarcinoma or small cell lung cancer groups compared with controls.
  • The groups differed. Lung cancer patients had a mean age of 60.76 years versus 39.54 years in controls (P<0.0001). Smokers made up 72.0% of patients (77 of 107) versus 39.0% of controls (39 of 100), P<0.0001.
• The authors' conclusion: The authors concluded that the b/b genotype and b allele of the eNOS intron 4, 27 bp repeat variant may be a genetic risk factor for developing epidermoid lung carcinoma in particular. They found that the Glu298Asp variant did not confer increased risk, and they called for larger prospective studies.
• Limitations the authors state:
  • The sample was small, about half the size of an earlier South Korean study. The authors called this the major limitation and suggested it may explain the lack of findings in the adenocarcinoma and small cell groups.
  • Serum nitric oxide levels were not measured.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Carcinogenic, Apoptosis, Angiogenesis.

Related studies

• Inducible nitric oxide synthase genetic polymorphism and risk of asbestosis — A. Franko, M. Dodič-Fikfak, et al. (2011)
• Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1 — Y. Soini, A. Puhakka, et al. (2001)
• Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos — H. Iguchi, S. Kojo, et al. (1996)
• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)
• Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma — Y. Soini, K. Kahlos, et al. (2000)
• Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells — S.H. Park, A.E. Aust (1998)

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