Background: 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 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. Methods: We 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. Results: In 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. Conclusion: The 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.

Background The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. Methods Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02–1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01–1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97–1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). Conclusions This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D' = 0.91 and r 2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.