The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study

Our plain-English summary of The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study, by M.S. Khella, A.M. Salem, O. Abdel-Rahman, et al (Genetic Testing and Molecular Biomarkers, 2018).

The study

• Authors: M.S. Khella, A.M. Salem, O. Abdel-Rahman, A.S. Saad
• Journal: Genetic Testing and Molecular Biomarkers
• Published: 2018;22(2):79-84
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk.

Materials And Methods: FTO rs9939609 (T >A) genotypes were screened using a TaqMan® Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design.

Results: In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025).

Conclusions: The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.

In plain English

This case–control study from Ain Shams University in Cairo, Egypt, examined whether a variant called rs9939609 in the FTO gene was associated with malignant pleural mesothelioma. The authors genotyped 86 patients with pathologically confirmed pleural mesothelioma who had been exposed to asbestos, recruited between April 2014 and February 2016. They compared them with 149 controls from the general population, recruited from Cairo suburbs with known heavy asbestos exposure. Asbestos levels were not measured quantitatively. After adjustment for age, gender and body mass index, people with one copy of the A variant (AT) had 2.48 times the odds of mesothelioma of people with TT (95% confidence interval 1.04 to 5.92). For two copies (AA) the odds ratio was 3.46 (0.99 to 12.01, p = 0.051), just above the 0.05 cutoff the authors used for statistical significance. People carrying at least one A (AT or AA) had an adjusted odds ratio of 2.63 compared with people with TT (1.13 to 6.12). The authors concluded the variant may be a genetic risk factor for mesothelioma. They noted their small sample, and that cases and controls differed in age, gender and body mass index.

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: Genetic association case–control study
• Who was studied: 235 unrelated Egyptian subjects: 86 patients with pathologically confirmed malignant pleural mesothelioma who had been exposed to asbestos, referred to Ain Shams University, Cairo, between April 2014 and February 2016, and 149 controls from the general population
• Exposure: FTO rs9939609 genotype (TT, AT, AA). The authors state that all subjects had asbestos exposure. Controls were matched for asbestos exposure by recruiting them from Cairo suburbs with known heavy exposure near asbestos factories. No fiber type was stated and exposure was not measured quantitatively.
• Main results:
  • Genotype distribution: in mesothelioma patients 17.4% TT, 62.8% AT, 19.8% AA; in controls 34.9% TT, 51% AT, 14.1% AA
  • The A-allele was associated with 1.6-fold higher odds of mesothelioma compared with the T-allele (95% CI 1.09–2.33, p = 0.019)
  • After adjustment for body mass index, age and gender, compared with TT: AT odds ratio 2.48 (95% CI 1.04–5.92, p = 0.04); AA odds ratio 3.46 (95% CI 0.99–12.01, p = 0.051), above the authors' significance threshold of p less than 0.05
  • Dominant model, adjusted for age, gender and body mass index: carriers of AT or AA had 2.63-fold higher odds of mesothelioma than TT carriers (95% CI 1.13–6.12, p = 0.025)
  • Genotype distributions agreed with Hardy–Weinberg equilibrium in the whole population and in controls, but deviated in the patient group
  • Among the 86 patients, no statistically significant association was found between genotype and clinicopathological characteristics
• The authors' conclusion: The authors concluded that the FTO rs9939609 polymorphism may be a genetic risk factor for malignant pleural mesothelioma, and that it should be studied in other populations with larger samples
• Limitations the authors state:
  • Relatively small sample size
  • Asbestos levels were not measured quantitatively
  • Cases and controls differed in age, body mass index and gender distribution; the authors adjusted for these

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Case-Control Study, Asbestos Exposure, Oxidative Stress, Inflammation, Carcinogenesis, confidence interval.

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