ArticleMolecular carcinogenesis2013
A functional trinucleotide repeat polymorphism in the 5'-untranslated region of the glutathione biosynthetic gene GCLC is associated with increased risk for lung and aerodigestive tract cancers.
Article in Molecular carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.European journal of nutrition · 2015Trial
- Glutathione contributes to alleviating hepatic injury via host-microbiome interaction and CAR-dependent pathway.Science China. Life sciences · 2025Article
- Article
- Implications of GCLC in prognosis and immunity of lung adenocarcinoma and multi-omics regulation mechanisms.BMC pulmonary medicine · 2024Article
- Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer.BMC cancer · 2021Article
- The role of polymorphisms in glutathione-related genes in asbestos-related diseases.Radiology and oncology · 2021Article
- An Integrated Approach for Preventing Oral Cavity and Oropharyngeal Cancers: Two Etiologies with Distinct and Shared Mechanisms of Carcinogenesis.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Review
- High GCLC level in tumor tissues is associated with poor prognosis of hepatocellular carcinoma after curative resection.Journal of Cancer · 2019Article
- Characterization of porcine simple sequence repeat variation on a population scale with genome resequencing data.Scientific reports · 2017Article
- Formaldehyde Induces Rho-Associated Kinase Activity to Evoke Airway Hyperresponsiveness.American journal of respiratory cell and molecular biology · 2016Article
- Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors.BioMed research international · 2015Review
- Glutathione defense mechanism in liver injury: insights from animal models.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Glutathione (GSH), the major intracellular antioxidant, protects against cancer development by detoxifying carcinogens and free radicals and strengthening the immune system. Recently, a GAG-trinucleotide repeat polymorphism in the 5'-untranslated region of the gene for the rate-limiting enzyme for GSH biosynthesis, γ-glutamine cysteine ligase (GCL), was shown to be associated with lowered GCL activity and GSH levels in vitro and in vivo. We tested the hypothesis that this functional polymorphism in GCL is associated with the risk for lung and aerodigestive tract cancers. To this end, we conducted a case-control study that included 375 lung cancer cases, 200 aerodigestive tract cancer cases, and 537 controls. GAG repeat genotype (4, 7, 8, 9, and 10 repeat alleles) was determined by capillary electrophoresis of PCR products from the repeat region of the GCL catalytic subunit (GCLC). Odds ratios (OR) were calculated by logistic regression and adjusted for risk factors, including age, sex, body mass index, and smoking history. The GAG-7/7 genotype was associated with a 1.9-fold increased risk of lung cancer and 2.6-fold increased risk of aerodigestive tract cancer compared to the wild-type GAG-9/9 (P < 0.05). Similarly, the GAG-7 allele was associated with an increased risk of lung cancer (OR = 1.5, P = 0.01) and aerodigestive tract cancer (OR = 2.3, P < 0.001) compared to subjects without GAG-7 allele. These findings suggest that GSH synthesis affects the risk of lung and aerodigestive tract cancers, and further implicates a role for oxidative stress in the development of these cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.