Association of PIN3 16-bp duplication polymorphism of TP53 with breast cancer risk in Mali and a meta-analysis

Brehima Diakite,Sellama Nadifi,Brian Joyce,Mercy Isichei,Lifang Hou,Erin Neuschler,Cheick Bougari Traore,Etienne Dembele,Jane L Holl,Jun Wang,Mamadou Lassine Keita,Oumar Kassogue,Yaya Kassogue,Guimogo Dolo,Mamoudou Maiga,Seydou Doumbia,Jonah Musa,Bakarou Kamate,Robert Murphy

doi:10.1186/s12881-020-01072-4

Abstract

BackgroundBreast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations.MethodsWe analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot.ResultsIn the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08–4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05–3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15–1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02–1.19; P = 0.01) models.ConclusionThe case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.

Highlights

Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of tumor protein p53 (TP53)
Several genes have been shown to be associated with an increased risk of breast cancer, such as damaged DNA repair genes (BRCA1 and BRCA2), tumor protein p53 (TP53), Checkpoint kinase 2 (CHEK2), methylenetetrahydrofolate reductase (MTHFR), fibroblast growth factor receptor 2 (FGFR2) and glutathione S-transferase mu 1 (GSTM1) [4]
Case control study We evaluated the association between PIN3 16-bp duplication polymorphism of TP53 and the risk of breast cancer in Malian women

Summary

Introduction

The most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. Recent report showed that in addition to clinical, lifestyle and environmental risk factors, an individual’s genetic background plays a crucial role in the development of breast cancer [3]. TP53, a tumor suppressor gene, is involved in the development of breast cancer, and in the development of other human cancers. This gene plays a significant role in the response to stress. The great heterogeneity reported in the TP53 in breast cancer may be linked to the geographic origin and ethnic differences of patients [8–10]

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