Lack of Association of C677T Methylenetetrahydrofolate Reductase Polymorphism with Breast Cancer Risk in Mali.

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.

Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis.

A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14-1.49), dominant model (OR = 1.36, 95% CI = 1.09-1.70), and additive model (OR = 1.25, 95% CI = 1.09-1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05. The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.

The influence of Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-17, TNF-A, MIF, STAT3 on lung cancer risk in Moroccan population.

To date, several studies have reported that key cytokines in the inflammatory system have important roles in the pathogenesis of cancer, notably in lung cancer. The aim of this case-control study, conducted for the first time in Moroccan population, was to investigate and to analyze the association of the following inflammatory cytokine genes Interleukin (IL)-6, Interleukin (IL)-8, Interleukin (IL)-10, Interleukin (IL)-17, Tumor Necrosis Factor-Alpha (TNFA), Macrophage migration Inhibitory Factor (MIF) and Signal Transducer and Activator of Transcription 3 (STAT3) with lung cancer risk in our patients. Firstly, the mRNA expression was assessed by a quantitative real time PCR in the peripheral blood of lung cancer patients and healthy subjects. Secondly, polymorphisms in the genes encoding cytokines were assessed in 160 lung cancer patients and 150 healthy controls. Genotyping analysis was performed with a Real-Time polymerase chain reaction using TaqMan® genotyping assays on a 7500 FAST Real-Time PCR System and Restriction Fragment Length PolymorphismPCR. Our results revealed a significant difference in mRNA expression levels of IL-6, IL-8, IL-10, IL-17 and TNFA genes in lung cancer patients compared to healthy subjects (P < 0.05). Among the studied genes, we found a significant association between lung cancer risk in our patients and the following polymorphisms IL-6 (rs1800795, rs1800796), IL-8 (rs4075, rs2227306), IL-17F (rs763780, rs2397084) and MIF (rs755622). In conclusion, the results of our study suggest that IL-6, IL-8, IL-10, IL-17 and MIF cytokine genes may aggravate lung cancer risk in the Moroccan population. However, further investigations are required to confirm our findings.

[Association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of sporadic colorectal cancer]. / Association du polymorphisme de la méthylènetétrahydrofolate réductase C677T avec le risque de cancer colorectal sporadique.

Colorectal cancer (CRC) is a major global public health problem. Folate metabolism is involved in DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Common MTHFR C677T polymorphism was correlated to CRC. This case-control study was conducted to analyze the association between this polymorphism and the risk of sporadic CRC in a Moroccan population. The study involved 76 patients with sporadic colorectal cancer confirmed histologically and 182 patients (control group) without a history of cancer. Deoxyribonucleic acid (DNA) was isolated from peripheral blood and genotypes were determined using PCR-RFLP. The risk of association was estimated using odds ratio (OR) with 95% confidence interval. Genotype frequency of MTHFR in patients and in the control group was CC 34.1%, CT 56.6%, TT 9.21%, CC 51.6%, CT 42.8% and TT 6% respectively. CT genotype and its combination with TT genotype and allele T were associated with an increased risk of CRC and with an OR of 2.02 (with 95% confidence interval [CI]: 1.14-3.58, p = 0.01), 2.05 (95 % CI: 1.18-3.58, p= 0.01) and 1.61 (95% CI: 1.07-2.40, p=0.02). Homozygous TT weren´t a protection factor in our study, with an OR of 2.30 (95% CI: 0.81-6.52, p = 0.11). There was a statistically significant association between the MTHFR C677T variant and the risk of occurrence of sporadic colorectal cancer in the studied population.

p.Arg72Pro polymorphism of P53 and breast cancer risk: a meta-analysis of case-control studies.

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.

The influence of DNMT3A and DNMT3B gene polymorphisms on acute myeloid leukemia risk in a Moroccan population.

Acute myeloid leukemia (AML) is a very complex disease that is linked to environmental, genetic and epigenetic factors. Several Studies have found that aberrations in DNA methylation process play a crucial role in leukemogenesis. The aim of this case control study was to evaluate the association between rs1569686, rs2424913 polymorphisms located in DNMT3B gene and rs7590760 polymorphism located in DNMT3A gene and AML risk in a Moroccan population. MATERIALS AND METHODS: The present study was conducted in 142 cases of AML and 179 control subjects from the Moroccan population. Genomic DNA was isolated from whole blood samples by salting-out method and the genotype of the three polymorphisms was determined by the PCR-RFLP technique. RESULTS: The study results indicated that rs1569686 polymorphism was significantly associated with the risk of AML in dominant model (OR=1.72, 95 % CI 1.01-2.95, P=0.04), but not in recessive model. In stratified analysis by gender, statistically significant association between the rs2424913 CT genotype and AML was found among males (OR=2.05, 95 % CI 1.00-4.19, P=0.04). Similarly, the rs1569686 TT genotype was associated with an increase risk of AML (OR=3.21, 95 % CI 1.15-8. 98, P=0.02), this association was also found under dominant genetic model (OR=2.47, 95 % CI 1.07-5. 67, P=0.03) among males. However, the rs2424913 polymorphism was not associated with AML. CONCLUSION: Our findings have shown that rs1569686 polymorphism might be a risk factor of AML in males. While, the rs2424913 polymorphism was not associated with AML. Further studies with a large sample size are needed to validate our results.

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

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.

Association of Multidrug Resistance Gene-1 (MDR1 C1236T) Polymorphism with the Risk of Acute Myeloid Leukemia in a Moroccan Population.

The human multidrug resistance MDR1 gene plays a crucial role in the absorption, transport, metabolism and elimination of harmful compounds. An impaired metabolism of these compounds related to genetic polymorphism may cause cancer such as acute myeloid leukemia AML. OBJECTIVE: The present study investigated the relationship between C1236T polymorphism and the risk of AML development in a sample of Moroccan population. METHODS: The present case-control study included 131 AML patients and 136 healthy controls. The MDR1 C1236T polymorphism was identified by PCR-RFLP method. Meta-analysis was performed to discuss our results. Statistical analyses were performed using SPSS, MetaGenyo and MedCalc. RESULTS: A positive association was found between the 1236TT mutant genotype and the risk of AML (OR 2.39; 95% CI 1.02-5.57, p= 0.04) compared to the wild type 1236CC. In addition, the recessive model revealed that carriers of 1236TT mutant genotype were more exposed to develop AML when compared to the combined 1236CC/CT genotype (OR: 2.27, CI: 1.01-5.05, p=0.04). The clinical parameters of AML showed no significant association. Meta-analysis demonstrated no statistically significant association between this polymorphism and AML susceptibility. CONCLUSION: Our study suggests that the MDR1C1236T polymorphism appears to be associated with the risk of AML. Further studies, including a large sample size, are needed to confirm these findings.

BRCA Mutational Status is a Promising Predictive Biomarker for Platinum- based Chemotherapy in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the lack of expression of estrogen receptors (ER), progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2). TNBC is associated with adverse clinical outcomes and high risk of metastasis. Currently, several clinical and translational reports are focusing on developing targeted therapies for this aggressive cancer. In addition to approved targeted drugs such as poly(ADP-ribose) polymerase inhibitors (PARPi) and immune-checkpoint inhibitors, platinum-based chemotherapy is still a cornerstone therapeutic option in TNBC. However, despite the observed improved outcomes with platinum- based chemotherapy in TNBC, there is still a large proportion of patients who do not respond to this treatment, hence, the need for predictive biomarkers to stratify TNBC patients and therefore, avoiding unwanted toxicities of these agents. With the emergence of genetic testing, several recent studies suggested mutations in breast cancer susceptibility gene (BRCA) in TNBC patients as important predictors of outcomes. These mutations alter the homologous recombination repair (HRR) mechanisms leading to genomic instability. Consequently, sensitivity to platinum-based treatments in this subpopulation of TNBC patients may be explained by cell death enhanced by deoxyribonucleic acid (DNA) damage induced by these potent anticancer drugs. Through this paper, we review several recent studies on this topic to better understand the mechanisms and discuss the potential of BRCA mutational status as a predictive biomarker of platinum-based chemotherapy in TNBC.

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population.

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 GSTM1-present/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.

Association of Variants in IL6-Related Genes with Lung Cancer Risk in Moroccan Population.

PURPOSE: Lung cancer is known to be a complex multifactorial disease, involving both genetic and environmental factors. The study of the different signaling pathways and the identification of the genes involved, will contribute to further understanding the pathogenesis of the disease, thus allowing the development of appropriate targeted treatments. Recently, the link between cancer and inflammation has become more evident and inflammation has been proposed as the seventh hallmark of cancer. Previous studies have suggested that key cytokines involved in inflammation may have an important role in the etiology of lung cancer. The aim of this study was to investigate whether common variants in inflammation-related genes: IL-6, IL6-R, and IL6-ST, influence lung cancer risk in Moroccan population. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R, and IL6-ST genes were assessed in 120 controls and 120 patients with confirmed lung cancer diagnosis. Genotyping analysis was performed with the TaqMan® allelic discrimination technology. The results were analyzed using SPSS 24.0 software. RESULTS: Among the studied SNPs, we found a significant association for the IL-6 (rs2069840) (OR = 1.63; 95% confidence interval 1.08-2.47; p = 0.01). No significant association was observed for the remaining SNPs of IL-6R (rs2228145) and IL-6ST (rs2228044) genes. CONCLUSION: Our results suggest the IL-6 (rs2069840) polymorphism may influence the occurrence of lung cancer in Moroccan patients.

Targeted methods for molecular characterization of EGFR mutational profile in lung cancer Moroccan cohort.

The study of EGFR gene mutational profile in NSCLC patients has a special clinical significance in the selection of patients for tyrosine-kinase inhibitors therapy. From 2017, the targeted therapy started to be accessible in public sector in Morocco, thus, the implementation of techniques for the molecular characterization of EGFR mutations in the laboratories became a necessity. The aim of this study was to present targeted methods "ADx-ARMS technology and the Idylla™ system" for the identification of EGFR mutational profile, methods that can be implemented in our clinical laboratories for routine analysis instead of outsourcing analysis to other countries. We conducted this study by processing 239 cases of NSCLC patients. Using the DNA extracted from the FFPE tissue, we evaluated somatic mutations in exons 18 to 21 of the tyrosine-kinase domain of EGFR gene by HRM-PCR combined to real time PCR "ADx-ARMS technology" and Idylla™ system. These sensitive methods showed that among the positive mutant cases, the distribution of mutations was as follows: 70% of patients having a deletion in exon 19, 15% in exon 21 (L858R), 7.5% in exon 20 and 7.5% in exon 18 (G719X). All of the positive EGFR mutations cases were adenocarcinoma and 42.1% of them were smokers. These results show the need to incorporate a quick and efficient method for the identification of EGFR mutation into routine practice in our laboratories, allowing more patients to benefit from targeted therapy.

Genetics of Glioblastoma in Moroccan population: Review of literature.

Glioblastoma is the most aggressive malignant type of central nervous system tumors. The literature review revealed that the most common genetic abnormalities in primary and secondary glioblastomas are IDH1 / 2 mutations, p53 mutations, and overexpression of EGFR. To our knowledge, this is the first Moroccan study to provide a global picture of genetic studies performed on Moroccan patients to describe genetic markers and their frequency in our population. An in-depth research in ScienceDirect and Pubmed on glioblastoma articles treated in Morocco, this research is based on the following keywords: glioblastoma in Morocco, primary glioblastoma in Morocco, secondary glioblastoma in Morocco. We found only three research articles on genomic alteration of IDH1 / 2, p53 and EGFR expression. The frequency of these gene mutations in our population was similar to those reported from other populations. Additional molecular studies need to be performed on other genes to describe other genetic markers in the Moroccan population.

The PTPN22 C1858T (R620W) functional polymorphism in inflammatory bowel disease.

OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858C→T) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients. RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.

The 72Pro Variant of the Tumor Protein 53 Is Associated with an Increased Breast Cancer Risk in the Moroccan Population.

BACKGROUND: The purpose of our case control study is to explore the potential association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism (rs1042522) with the risk of breast cancer (BC) development in the Moroccan population. METHODS AND RESULTS: The study population consisted of 125 female patients with confirmed BC and 126 healthy controls. DNA samples were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay method using BstUI restriction enzyme. We showed that the homozygous genotype of TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2, 95% CI 1.07-4.54, p = 0.03). The dominant and additive models of TP53 Pro allele were also correlated to the risk of BC (OR 2.13, 95% CI 1.07-4.23, p = 0.02 and OR 1.49, 95% CI 1.03-2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72 variant was associated with protection against BC, either in the homozygous genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22-0.93, p = 0.03; OR 0.46, 95% CI 0.23-0.92, p = 0.029 and OR 0.67, 95% CI 0.46-0.97, p = 0.03, respectively). CONCLUSION: Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population.

The Human papillomavirus among women living with Human Immunodeficiency Virus in Morocco: A prospective cross-sectional study.

INTRODUCTION: Women infected with human immunodeficiency virus (HIV) have a higher risk of contracting human papillomavirus (HPV) infections and are more prone to develop cervical cancer. The objective of this study was to determine the prevalence of HPV and its association with risk factors among Moroccan women living with HIV/AIDS. METHODOLOGY: We enrolled 251 HIV-infected non-pregnant women in Morocco from February 2013 to September 2016. Sociodemographic, lifestyles, behavioral and clinical data were collected. Polymerase chain reaction followed by sequencing were performed for molecular detection and HPV genotyping in cervical samples, respectively. RESULTS: Abnormal cervical smears were found in 34/246 patients (13.82%). The overall prevalence of HPV was 74.50%. HPV 58 was the most prevalent (39.29%) followed by HPV 18 (10.71%), HPV 70 (8.93%), HPV 33 (7.14%), HPV 6 (6.25%) and other genotypes (< 3%). Overall, high-risk HPV (HR-HPV) types were present in 75% (84/112) of patients and the prevalence of HR-HPV types in samples with abnormal Pap was higher than in normal Pap (55/83, 66.27% vs. 28/83, 33.33%, p < 0.0001). Univariate analyses showed that none of the socio-demographic and behaviors factors was associated with HPV infection. Moreover, Pap results were not affected by HPV status (p = 0.532). Whereas, CD4 T-cell counts above 200/mm3 at enrolment were apparently not protective to HPV infection. We found a high prevalence of HPV infection and HR-HPV types among HIV-positive women that significantly associated with abnormal Pap. CONCLUSION: Our findings suggest a high prevalence of HPV infection with high-risk types was observed among HIV-positive women warrant to implement a regular screening by Pap smear.

Genetic investigation of XPA gene: high frequency of the c.682C>T mutation in Moroccan XP patients with moderate clinical profile.

OBJECTIVE: Xeroderma pigmentosum (XP) is a genetically and clinically heterogeneous disease, associated with an inherited defect in one of eight different genes (XPA to XPG and XPV). In addition to the early onset of the skin manifestations, the XP group A is marked by the presence of a mild to severe neural disorders which appear tardily and worsens with age. In this study, 9 patients with moderate clinical profile belonging to 6 XP families were recruited to determine the XPA mutational spectrum in Morocco, using the direct sequencing of the whole coding region of the XPA gene. RESULTS: The genetic investigation of the XPA gene showed that 7 from 9 patients were homozygous for the c.682C>T, p.Arg228X mutation, while all their investigated family members were heterozygous. The frequency of this mutation was estimated to be 83.33% (5/6 families) .The molecular analysis of the 5 other exons of the XPA gene, showed that the 2 negative siblings carried no mutation in the XPA gene. This finding suggests that c.682C>T (p.Arg228X) mutation is relatively associated with moderate phenotype in XP group A Moroccan families; this result will also contribute to improve the molecular diagnosis of XP disease in Moroccan patients.

TP53 R72P Polymorphism and Susceptibility to Human Papillomavirus Infection Among Women With Human Immunodeficiency Virus in Morocco: A Case-control Study.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. HPV is the main causative agent for cervical cancer. The HPV oncoprotein E6 binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of TP53 R72P polymorphism binds more ardently with HPV E6 than the Pro variant. Here, we investigated whether TP53 R72P gene variant, rs104252, was associated with susceptibility to HPV infection in women with human immunodeficiency virus (HIV). METHODS: We analyzed 200 HPV-positive and 68 uninfected women with HIV. Genomic DNA was isolated from cervical swab. The TP53 R72P polymorphism was genotyped by PCR-RFLP. Unconditional logistic regression was used to assess the association between polymorphism and the clinical, lifestyle, and behavioral data. RESULTS: The genotype and allele frequencies of rs104252 variant did not differ between women without or with HPV infection (P > 0.05). Moreover, the p53 polymorphism was not associated with cervical cytology. In contrast, when we analyzed according to behavior factors, the P72P genotype was more frequent among HPV-positive smoker women. However, no significant relationship was found between alcohol, contraceptive use, and number of partners with TP53 R72P genotype distributions among HPV-positive cases (P > 0.05). CONCLUSIONS: The R72 variant of p53 R72P is not associated with HPV infection and progression of lesions. There was no association between this variant and behavior factors in HPV-positive cases. The P72P genotype may be more frequent among HPV-positive smoker women.

Risk of colorectal cancer and clotting factor gene polymorphisms in Moroccan Population.

BACKGROUND: Venous thrombosis has been described as a common complication for cancer patients. The association between clotting factor gene polymorphisms and the risk of colorectal cancer has been evidenced. The aim of the present study was to investigate the association of G20210A factor II prothrombin (FII) and factor V Leiden ( FVL) G1691A with the risk of colorectal cancer(CRC). METHODS AND RESULTS: Genotyping of FVL and G20210A FII was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 76 patients with CRC as well as 182 controls. No significant difference in FVL gene variations was observed between cases and controls. However, with regard to the G20210A FII, the homozygous mutated genotype AA was associated with an increased risk of CRC. A significant association between the G20210A FII mutation and the risk of CRC was identified using recessive (OR=57.63, 95% CI: 3.33-997.26, P=0.0053), dominant (OR=27.87, 95% CI: 12.67 -61.28, P<0, 0001) and additive (OR=21.24, 95% CI: 10.45-43.16, P<0, 0001) models. No statistical difference was observed in parameters such as sex, age and positive family history for cancer. CONCLUSION: Our results did not support an effect of FVL gene on CRC risk and suggested that the G20210A FII prothrombin gene variant may be a risk factor for CRC in Moroccan population.

Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis.

BACKGROUND: Breast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population. METHODS: A case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed. RESULTS: Genotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006). CONCLUSIONS: We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.