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The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study
Mina S Khella1, Ahmed M Salem2, Omar Abdel-Rahman3
11 Department of Biochemistry, Faculty of Pharmacy, Ain Shams University , Abbassia, Cairo, Egypt .
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.
Insights
The FTO gene rs9939609 polymorphism may increase the risk of malignant pleural mesothelioma (MPM). This genetic factor, linked to inflammation, warrants further investigation in diverse populations and cancers.
Area of Science:
- Genetics
- Oncology
- Environmental Health
Background:
- Malignant pleural mesothelioma (MPM) is strongly linked to asbestos exposure.
- Genetic factors may also contribute to MPM development.
- The FTO gene rs9939609 polymorphism is associated with other cancers and inflammation.
Purpose of the Study:
- To investigate the association between the FTO rs9939609 polymorphism and MPM risk.
- To explore the role of genetic susceptibility in asbestos-related carcinogenesis.
Main Methods:
- A case-control study was conducted with 235 Egyptian subjects (86 MPM patients, 149 controls).
- FTO rs9939609 genotypes were analyzed using TaqMan® Genotyping Assay.
- Statistical analysis included chi-square tests and logistic regression.
Main Results:
- The AT and AA genotypes of FTO rs9939609 were associated with increased odds of MPM in additive models.
- The AT/AA genotypes showed a significant increase in MPM odds in the dominant genetic model.
- Adjustments were made for body mass index, age, and gender.
Conclusions:
- The FTO rs9939609 polymorphism may represent a genetic risk factor for MPM.
- This finding suggests a link between FTO gene variation and cancer susceptibility.
- Further research with larger sample sizes and diverse populations is recommended.
