High Heterozygosity in SNPs of TNF alpha Gene of Women Accessing Breast Cancer Care at a Tertiary Health Facility in Southwest Nigeria
Nanfizat Abiket Alamukii1,2*, Abayomi Odetunde2, Chinedum Peace Babalola2,,3 Adeyinka Gladys Falusi2, Roseangela Ifeyinwa Nwuba1,4
1Department of Zoology, Faculty of Science, University of Ibadan, Nigeria; 2Genetics Research Unit, Institute for Advance Medical Research and Training (IAMRAT), University College Hospital (UCH), University of Ibadan, Nigeria; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Nigeria; 4Department of Biological Sciences, Faculty of science, University of Medical Sciences, Ondo, Nigeria
Introduction: Single Nucleotide Polymorphisms (SNPs) at the promoter region of TNFα gene are involved in the regulation of its expression. Alleles of these SNPs such as TNFα 308-A have been known to increase the production TNF protein. The presence of TNFα at the microevironment of certain tumours including breast cancer have been recorded. We genotyped the SNPs of TNFα and its receptors in breast cancer patients and control individuals to determine their role in the development and progression of breast cancer among women accessing care at a tertiary health facility in southwest Nigeria.
Methodology: This is a case control study of 200 consenting women recruited from the University College Hospital, Ibadan. The study was approved by the UI/UCH Ethical Review Board/Committee. DNA was extracted from blood samples collected from each participant. Allele-specific polymerase chain reaction was used to genotype various SNPS of TNFα and its receptors [TNFα (488 G/A, 238 G/A, 308 G/A, 859 C/T) and its receptor (TNFR1A+IV56+10 -G/A)].
Results: These showed very high heterozygosity of all the TNFα SNPs genotyped in the population which is a deviation from Hardy-Weinberg rule (P<0.0001). There was a significant difference (p-=0.0213) between cases and control for genotypes GA, AA & GG of TNFα 308. On the other hand, there were no significant differences between case and control for genotypes GA, GG & AA of TNFα 488, 238, 380 TNFR1A+IV56+10, and CC, CT, TT of TNFα 859 (P=0.2841, 0.7859, 0.3014 & 0.4922 respectively).
Conclusion: The genotypic results indicate a selection for heterozygote alleles within the population which although not yet linked to breast cancer, may be important in the expression of TNF gene for survival the geographical region. The significant difference in the genotypes of TNFα 308 between breast cancer patients and control individuals is a possible indicator that this SNP may have an important role in the development and progression of breast cancer among Nigerian women.
Keywords: Breast cancer, TNFα, SNPs heterozygosity, Nigerian women.