To the Editor
Chronic inflammation and pro-inflammatory mediators including tumor necrosis factor alpha (TNF-α) may increase the risk of gastrointestinal (GI) cancer Citation[1]. Recently, TNF-α-238 G/A gene promoter polymorphism was shown to be associated with immune-mediated disorders Citation[2] and certain types of cancers, including gastric, uterine cervical, and colorectal (CRC) cancers Citation[3]. No association was found between the TNF-α-308 alleles and malignancy Citation[3], Citation[5]. The aim of our report was to test if -238 G and A alleles were related to possibility of developing CRC in Iranian patients.
Genotype differences between 51 histopathologically verified cases from Tehran hospitals and 46 matched controls were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Citation[4] and compared following study protocol approved by the Center Ethical Committee. Data were χ2 tested by calculating the expected frequencies of each genotype and comparing them to the observed values.
In the control group, the frequency of G allele was 99% and that of A allele was 1% (). The corresponding figures for the case group were 100% and 0%. The TNF-α-238 genotype frequencies for patients and controls were not significantly different (p-value = 0.474). Hardy Weinberg analyses of the genotype data pointed to the equilibrium in both controls (χ2=0.09; p = 0.973) and cases (χ2=0; p = 1).
Table I. Genotype and allele distributions of the TNF-α-238 G/A polymorphism in case and control populations.
Thus, we reported no relationship between TNF-α-238 polymorphism and risk of CRC in Tehran. Various ethnic groups of Iran are now represented in Tehran, and most of them have roughly the same share of capital's population as in the country. Previous studies have shown that the TNF-α-238A allele potentially diminishing the expression of this mediator is associated with lower risk of cancer, including CRC Citation[3]. However, our results do not support a link between this polymorphism and CRC. Several causes may explain the discrepancy between these previous findings and the results of our study. The earlier reported association could have resulted from other confounders. Alternatively, true association might exist only in groups of a particular ethnic origin or, most likely, of a similar genetic background. For complex GI disorders, various genetic and environmental factors may interact to influence the development of tumor. Further analysis and a larger sample size are required to clarify the role of TNF-α polymorphisms in the cause and progression of CRC.
Acknowledgements
We wish to thank Dr. Saeed Talebi for his help with the statistical analysis.
References
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- Fabris M, Di PE, D'Elia A, Damante G, Sinigaglia L, Ferraccioli G. Tumor necrosis factor-alpha gene polymorphism in severe and mild-moderate rheumatoid arthritis. J Rheumatol 2002; 29: 29–33
- Jang WH, Yang YI, Yea SS, Lee YJ, Chun JH, Kim HI, et al. The -238 tumor necrosis factor-alpha promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett 2001; 166: 41–6
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