The functional TNF-α-308G > a single-nucleotide polymorphism (rs1800629): association with the predictive indices of breast cancer carcinogenesis.

Background: Compared with all other cancer types, Breast cancer (BC) among women has now exceeded them all as the primary reason for cancer worldwide. The BC represents 11.7% of all cancer cases and accounts for a predestined 2.3 million new cases. It is the fourth primary reason for cancer-associated deaths in women. With a staggering 200-400% increase in the relative incidence of BC in Egypt, there is an urgent need for new diagnostic or predictive markers.

Purpose: The current investigation aims to explore the connection of the functional TNF-α^-308G > A (rs1800629) single-nucleotide polymorphism (SNP) with different breast cancer predictive indices.

Methods: The ARMS-PCR method was used for genotyping TNF-α^-308G > A SNP. Three groups were recruited for the study: 79 patients with benign breast inflammation (BBI); 163 with breast cancer (BC) and 144 controls (C).

Results: The TNF-α^-308G > A SNP was distributed among different groups in a unique pattern; in the control group 63.9% of cases were in the GG, 34% were in the GA, and 2.1% were in the AA. The BC group had 14% GG, 79% GA, and 7% AA, while the BBI group had 24% GG, 76% GA, and 0% AA. The AA genotype and A allele represented a strong significant correlation with risk factors in the BC group (OR_AA: 14.67 [95% CI = 3.78-56.91] and OR_A: 0.27 [95% CI = 0.19-0.39], respectively; P < 0.0001) in contrast to the control group. However, in the BBI group, a strong significant correlation was noted with the GA genotype (OR_GA: 5.93 [95% CI = 3.18-11.04] P < 0.0001). In the BC group, the AA genotype shows a significant increase in Nottingham Prognostic Index (NPI) in positive ER and PR in contrast to the relevant negative ones (P = 0.02 and 0.002, respectively). However, the GA genotype significantly increased NPI in positive Her2 and metastatic patients (P = 0.03 and 0.01, respectively).

Conclusion: This research is the first to correlate TNF-α^-308G > A (rs1800629) SNP in Egyptian BC patients. The A allele, GA & AA genotypes, and the Overdominant model of the TNF-α^-308G > A gene variants were recorded as prognostic risk factors for BC carcinogenesis.