BARRIERS TO EARLY DIAGNOSIS, TUMOUR NECROSIS FACTOR AND RECEPTOR GENETIC VARIANTS AS POSSIBLE PREDICTORS FOR BREAST CANCER AMONG NIGERIAN WOMEN

Abstract

Breast cancer is a major public health concern and early diagnosis is important in the treatment of the disease. In Nigeria, there has been an increase in breast cancer-related deaths, mostly because of delayed diagnosis due to reliance on clinical manifestation. Previous studies in Nigeria, identified mutant genes associated with breast cancer, but with limited information on Tumour Necrosis Factor-alpha (TNF-α) gene. The TNF-α is a cytokine that plays a significant role in initiation and progression of breast cancer. Therefore, this study was designed to determine the epidemiological factors affecting early diagnosis of breast cancer and identify key genetic variants of TNF-α and its receptor as potential predictors for breast cancer in Nigerian women. This study was carried out at the University College Hospital, Ibadan, Nigeria from May 2017 to July 2021. Interviews were conducted with 25 breast cancer patients and 10 health workers using purposive sampling techniques. In the case-control quantitative study, 100 cases and 100 controls were recruited by randomised sampling. Sociodemographics were documented, and blood samples collected from each participant. The TNF-α and its receptor levels were quantified by ELISA, and TNF-α (488 G/A, 238 G/A, 308 G/A, 859 C/T, 1032 C/T) and its receptor (TNFR1A+IV56+10 -G /A) alleles were genotyped by allele specific PCR. Sequencing of TNF-α isolates was done using a nanopore sequencer. Interviews were transcribed and analysed using the thematic narrative. Descriptive statistics, unpaired t-Test, ANOVA and Fisher’s exact test were used to analyse results with odd ratios at α0.05. Breast self-examination, a post-symptomatic diagnostic procedure, emerged as the major factor (88.0%) preventing effective early diagnosis of breast cancer in health facilities. Other factors included inadequate awareness, cost of diagnosis, health insurance scheme, alternative medicine and religious belief. The age of breast cancer patients was 45.81±10.66 years and most of the participants (96.0%) had no family history of breast cancer. Eighty percent of cases never used birth control, while 95.0% had never taken fertility hormone pills. At diagnosis, 58.0% of cases presented with Grade 2 tumour. The TNF-α level was significantly lower in cases compared to controls and correlated with tumour grades (R2=0.12). Soluble-TNF-α receptor levels were not significantly different between cases and controls. Five alleles showed a significantvii association with breast cancer: TNF-α 488G (OR=0.24, 95% CI= 0.08-0.74), TNF-α 380G (OR= 0.51, 95%CI= 0.51-0.93), TNF-α 308A, OR = 0.33, 95%CI=0.14-0.78), and TNFR1A+IV56+10-G (OR= 0.35, 95% CI= 0.19-0.68) TNF-α 1032C (OR= 2.08 CI= 1.18-3.65). Other alleles: TNF-α488A, 238G/A, 859C/T, 380A, 1032T and TNFR1A+IV56+10-A showed no association with breast cancer. TNF-α 488G, 308A and 1032C were associated with TNF-α levels in cases, while TNF-α 488G, 238A and 1032T were associated with TNF-α levels in controls. The presence of single nucleotide polymorphisms of TNF-α was confirmed through sequence alignment. Occurrence of breast cancer among Nigerian women is mostly sporadic and reliance on breast self-examination appears to be ineffective for early diagnosis. The Tumour Necrosis Factor-alpha gene variants (TNF-α 488G, 308A, and 1032C) might be predictors for breast cancer among Nigerian women.