Surgery for primary malignant tumors of the abdominal wall: experiences of three African surgical oncology units and review of the literature.

BACKGROUND AND OBJECTIVES: Tumors of the abdominal wall are uncommon but diverse. The surgical challenge is double. The tumor must be completely removed and the abdominal wall repaired. Our aim was to describe the indications, techniques, and results of surgery on these tumors in an African context. METHODS: Retrospective, multicentric and descriptive study conducted in three West African surgical oncology units. We included all abdominal wall tumors followed up between January 2010 and October 2022. Histological type, size, surgical procedure, and method of abdominal wall repair were considered. Survival was calculated using the Kaplan-Meier method and comparisons of proportions were made using the Student t test. RESULTS: We registered 62 tumors of the abdominal wall and we operated on 41 (66.1%). The mean size of the tumors was 14.3 ± 26 cm. Dermatofibrosarcoma and desmoid tumor were present in 33 and 3 cases respectively. In 31.7% of cases in addition to the tumour, the resections carried away the muscular aponeurotic plane. Parietal resections required the use of a two-sided prosthesis in 6 cases. In 13 cases, we used skin flaps. The resections margins were invaded in 5 cases and revision surgery was performed in all of them. Incisional hernia was noticed in 2 cases. The tumor recurrence rate was 12.2% with an average time of 13 months until occurrence. Overall survival at 3 years was 80%. CONCLUSIONS: Surgery is the mainstay of treatment for abdominal wall tumors. It must combine tumor resections and parietal repair. Cancer surgeons need to be trained in abdominal wall repair.

Issues in the surgical management of skin squamous cell cancers in albinos-experience of two surgical oncology units in Burkina Faso.

BACKGROUND AND OBJECTIVES: Skin cancers in albinos are frequent in sunny countries. The surgeon plays a crucial role in their treatment. The objective was to describe the challenges of surgical management of skin cancer in albinos. METHODS: Retrospective, descriptive, and multicenter study on skin cancer surgery in albinos performed over the past 14 years in Ouagadougou. We were interested in surgery indications, techniques, and results. Survival was assessed using the Kaplan-Meier method. Comparisons of proportions were made by Student's t-test. RESULTS: The cancers were multiple synchronous in 41.3%. We identified 46 albinos with 71 skin cancers. Surgery was performed in 93%. Lesions were located on the back, upper limbs, and head and face in 40.9%, 30.3%, and 16.7%, respectively. Precancerous lesions were treated concomitantly in 23.6%. The surgery consisted of a lumpectomy. Direct suturing and mobilization of flaps allowed skin coverage in 17.9% and 34.3%, respectively. Lymph node dissection was associated with the limbs in 73.1% of localizations. The average number of lymph nodes removed was 11, with extremes of 7 and 14. Node invasion was noted in 16 out of 19 cases. The resection margins were invaded in 7.5% and required surgical revision. Recurrences were noted in 8.9% of cases. Overall 2-year survival rate was 55.8%. CONCLUSIONS: Surgery must meet the triple challenge of treating single or multiple synchronous cancers, precancerous lesions, and allowing good healing. Early diagnosis would reduce the rate of secondary healing and improve survival. The absence of extemporaneous histology and the large size of the tumors associated with the delay in diagnosis meant that surgery, whenever possible, was limited to wide and deep resection, to ensure healthy margins.

Dermatofibrosarcoma protuberans surgery: Experiences of four African surgical oncology units and literature review.

BACKGROUND AND OBJECTIVES: Dermatofibrosarcoma is a locally malignant tumor. This gives surgery a place of choice. The advent of imatinib has improved outcomes. Our aim is to describe the indications, techniques and results of surgery. METHODS: A retrospective, multicenter, descriptive study conducted in four West African surgical oncology units. It covers dermatofibrosarcoma surgery performed between January 1, 1988 and December 31, 2020. We took into account the surgical procedure, the mode of skin coverage, adjuvant treatments and survival. Comparisons were possible using Student's t-test and Pearson's χ2 . RESULTS: We recorded 81 cases of dermatofibrosarcoma. Surgery was effective in 90.1% of cases. Wide resection was the principle with a mean resection margin of 3.8 ± 1.9 cm. healing by primary intention, flaps and healing by secondary intention were the methods of skin coverage in 30.1%, 24.7% and 41.1% respectively. The type of skin coverage was related to the topography and size of the tumor (p < 0.0001). The healing time is associated with the type of skin cover. The recurrence rate was not related to the type of skin coverage (p = 0.8). CONCLUSIONS: Wide and deep resection in the absence of Mohs micrographic surgery ensures healthy margins. Oncoplasty reduces the healing time without increasing the risk of recurrence.

Female genital mutilation and noninvasive cervical abnormalities and invasive cervical cancer in Senegal, West Africa: A retrospective study.

Female genital mutilation or cutting (FGM/C) is a traditional practice that affects a significant portion of women in sub-Saharan Africa, Egypt, areas of the Middle East and some countries in Asia. While clinical and epidemiological studies have established a close association between inflammation and carcinogenesis, particularly in epithelial cancers, the relationship between FGM/C and cervical cancer is not well known. We performed a secondary analysis using combined data from six research studies conducted in and around Dakar, Senegal from 1994 to 2012. Study subjects included both asymptomatic women who presented to outpatient clinics but were screened for cervical cancer, and women with cancer symptoms who were referred for cervical cancer treatment. We used unconditional logistic regression to estimate adjusted pooled odds ratios (ORs) and 95% confidence intervals (CI) for associations between FGM/C and (1) Invasive cervical cancer (ICC) and (2) noninvasive cervical abnormalities. After adjusting for confounding, women with ICC were 2.50 times more likely to have undergone FGM/C than women without cervical abnormalities (95% CI, 1.28-4.91). Restricting to HPV-positive women increased the strength of the association (OR = 4.23; 95% CI 1.73-10.32). No significant associations between FGM/C and noninvasive cervical abnormalities were observed, except in commercial sex workers with FGM/C (OR = 2.01; 95% CI 1.19-3.40). The potential increased risk for ICC suggested by our study warrants further examination. Study results may impact cancer prevention efforts in populations where FGM/C is practiced and draw awareness to the additional health risks associated with FGM/C.

Novel BRCA2 pathogenic variant c.5219 T > G; p.(Leu1740Ter) in a consanguineous Senegalese family with hereditary breast cancer.

BACKGROUND: Pathogenic variants associated with hereditary breast cancer have been reported for BRCA1 and BRCA2 (BRCA1/2) genes in patients from multiple ethnicities, but limited information is available from sub-Saharan African populations. We report a BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. METHODS: An index case from a consanguineous family and nineteen healthy female relatives were recruited after informed consent. Along with this family, 14 other index cases with family history of breast cancer were also recruited. For the control populations we recruited 48 healthy women with no cancer diagnosis and 48 women diagnosed with sporadic breast cancer without family history. Genomic DNA was extracted from peripheral blood. All BRCA2 exons were amplified by PCR and sequenced. Sequences were compared to the BRCA2 GenBank reference sequence (NM_000059.3) using Alamut Software. RESULTS: We identified a novel nonsense pathogenic variant c.5219 T > G; p.(Leu1740Ter) in exon 11 of BRCA2 in the index case. The pathogenic variant was also identified in three sisters and one daughter, but was absent in the controls and unrelated cases. CONCLUSIONS: This is the first report of a novel BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. This result confirms the diversity of hereditary breast cancer pathogenic variants across populations and extends our knowledge of genetic susceptibility to breast cancer in Africa.

Male breast cancer: diagnosis stages, treatment and survival in a country with limited resources (Burkina Faso).

BACKGROUND: Male breast cancer is a rare and less known disease. Therapeutic modalities affect survival. In Burkina Faso, male breast cancers are diagnosed in everyday practice, but the prognosis at short-, middle-, and long-term remains unknown. The objective of this study is to study the diagnosis stages, therapeutic modalities, and 5-year survival in male breast cancer at the General Surgery Unit of Yalgado Ouedraogo University Hospital from 1990 to 2009. METHODS: A cohort longitudinal study concerning cases of breast cancer diagnosed in man. Survival was assessed using the Kaplan-Meier method and survival curves were compared through the LogRank test. RESULTS: Fifty-one cases of male breast cancer were followed-up, i.e., 2.6% of all breast cancers. Stages III and IV represented 88% of cases. Eleven patients (21.6%) were at metastatic stage. Patients were operated in 60.8% of cases. The surgery included axillary dissection in 25 (80.6%) out of 31 cases. Lumpectomy was performed on 6.5% of patients (2 cases). Fifteen (29.4%) and 11 (21.6%) patients underwent chemotherapy and hormonal therapy, respectively. The FAC protocol was mostly used. Radiation therapy was possible in two cases. The median deadline for follow-up was 14.8 months. A local recurrence was noticed in 3.2% of cases. The overall 5-year survival rate was 49.9%. The median survival was over 5 years for stages I and II. It was 54 down to 36 months for stages III and IV. CONCLUSION: Diagnosis is late. The lack of immunohistochemistry makes it difficult to define the proportion of their hormonal dependence. Surgery is the basic treatment. Five-year survival is slow and the median survival depends on the diagnosis stage. It can be improved through awareness-raising campaigns and the conduct of individual screening.

Human papillomavirus infection in women in four regions of Senegal.

Cervical cancer is the most frequent cancer among women in Senegal. However, there are few data concerning the human papillomavirus (HPV) types inducing neoplasia and cervical cancers and their prevalence in the general population of Senegal. The aim of this study is to determine the prevalence of HPV infection in Senegalese women aged 18 years and older in Dakar Region and three other regions. Cervical samples were collected from 498 women aged 18-80 years (mean, 42.1 years) in Dakar Region. Also, 438 samples were collected from three other regions: Thiès, Saint-Louis, and Louga. The samples were screened for 21 HPV genotypes using an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG). The prevalence of high risk (HR)-HPV in Dakar Region was 17.4%. HPV 52 (3.2%) was the most prevalent HPV type, followed by HPV 31 (3.0%) and HPV 16, 45, and 53 (all 2.8%). In the Thiès, Saint-Louis, and Louga Regions, the prevalence of HR-HPV was 23.2%, 13.1%, and 19.4%, respectively. The study revealed the specificity of HPV prevalence in Dakar Region and other regions of Senegal. The observed patterns show some differences compared with other regions of the world. These findings raise the possibility that, in addition to HPV 16 and HPV 18, other HPV types should be considered for a vaccination program in Senegal. However, additional studies to determine the HPV type distribution in cervical cancer specimens in Senegal are required to further corroborate this hypothesis.

Genetic contribution of breast cancer genes in women of black African origin.

Breast cancer (BC) is an increasing public health issue worldwide. BC incidence and mortality rates are rising in transitioning countries in Africa, with the most rapid increase occurring in Sub-Saharan Africa (SSA). Female BC represents 25.8% of all cancer diagnosis in SSA. Early age at onset, high grade and triple negative tumors are hallmarks of BC in this region, associated with germline pathogenic variants in susceptibility genes. While several genes have been associated with genetic predisposition (BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1, STK11, ATM, CHEK2, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, … ), most studies have reported contribution of BRCA1 and BRCA2 pathogenic variants. Genetic contribution of BRCA genes has been estimated at 27% in Caucasian women. Available data from population of African origin are scarce and have mainly focused on pathogenic variants of BRCA1 and BRCA2. Reports from main studies on large sample size highlighted that BRCA1 still the major gene associated with BC in SSA. In addition, BRCA2, PALB2, and P53, are also on the top major genes with high penetrance, associated with BC. Mutation spectrum of BC genes in black African women seems to be different from Caucasian with increasing number of founder mutations identified. We hypothesis that the genetic contribution of known BC genes may be different between women of black African origin compared to Caucasians. In this review we explore the genetic contribution of known breast cancer genes in women of African origin, and discuss perspectives for prevention and patients care strategies in the era of precision medicine.

Gene expression profiling of peripheral blood mononuclear cells from women with cervical lesions reveals new markers of cancer.

Cervical cancer (CC) is a multifactorial disease of which human papillomavirus (HPV) is the main etiological agent. Despite cervical Pap smear screening and anti­HPV vaccination, CC remains a major public health issue. Identification of specific gene expression signatures in the blood could allow better insight into the immune response of CC and could provide valuable information for the development of novel biomarkers. The present study performed a transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from Senegalese patients with CC (n=31), low­grade cervical intraepithelial neoplasia (CIN1; n=27) and from healthy control (CTR) subjects (n=29). Individuals in the CIN1 and CTR groups exhibited similar patterns in gene expression. A total of 182 genes were revealed to be differentially expressed in patients with CC compared with individuals in the CIN1 and CTR groups. The IL1R2, IL18R1, MMP9 and FKBP5 genes were the most upregulated, whereas the T­cell receptor α gene TRA was the most downregulated in the CC group compared with in the CIN1 and CTR groups. The pathway enrichment analysis of the differentially expressed genes revealed pathways directly and indirectly linked to inflammation. To the best of our knowledge, the present study is the first large transcriptomic study on CC performed using PBMCs from African women; the results revealed the involvement of genes and pathways related to inflammation, most notably the IL­1 pathway, and the involvement of downregulation of the T­cell receptor α, a key component of the immune response. Several of the stated genes have already been reported in other cancer studies as putative blood biomarkers, thus reinforcing the requirement for deeper investigation. These findings may aid in the development of innovative clinical biomarkers for CC prevention and should be further replicated in other populations.

Survival of patients operated on for breast cancer in Ouagadougou/Burkina Faso.

BACKGROUND AND OBJECTIVES: Breast cancer is the most common cancer in women. The objective is to study the survival of patients operated on for breast cancer. METHODS: Descriptive and analytical study of the survival of patients operated on for breast cancer between January 1, 2013 and December 31, 2020 in Ouagadougou. Survival was assessed by the Kaplan-Meier method and comparisons by the log-rank test. Prognostic factors were determined using the Cox model. RESULTS: We collected 550 cases. Overall survival at 5 years was 66.2%. Those under 30 years of age had a low 5-year overall survival (53%). The 5-year overall survival was poor in rural patients (63.5%), triple-negative patients (77.2%), HER2+ patients (50.5%) and stage IV patients (29.8%). In multivariate analysis, higher education (p < 0.001) and higher socioeconomic level (p < 0.001) were associated with better prognoses. CONCLUSIONS: The survival of patients operated on for breast cancer remains to be improved. It is influenced by multiple factors especially the socio-economic and educational level of the patients.

The outcomes of palliative surgical treatment in a context of rising incidence of gastro intestinal cancers in Burkina Faso, Africa.

BACKGROUND AND OBJECTIVES: Digestive cancers are frequent and of late diagnosis in Africa. Palliative surgery therefore plays an important role. Our objective is to describe its indications, techniques and results in primary digestive cancers. METHODS: Retrospective, bicentric, descriptive study of palliative surgery for primary digestive cancer, performed in Ouagadougou over the last twelve years. The results were assessed according to the degree of improvement in the patients' quality of life. We divided the patients into four groups according to the improvement of the quality of life after the operation. The results were considered very satisfactory when the symptoms disappeared completely. They were considered satisfactory when the symptoms decreased in intensity. They were unsatisfactory when the symptoms kept the same intensity. They were considered poor when the symptoms persisted with greater intensity. RESULTS: Six hundred and thirty-nine palliative digestive cancer surgeries were performed. All patients had clinical symptoms deteriorating their quality of life (56.7%) or even a surgical emergency (43.3%). Biliodigestive diversion, gastroentero-anastomosis and colostomy were the palliative procedures performed respectively in 26.6%, 16.9%, and 34.1%. Complications were noted in 11.7%. These were digestive fistulas in 9 cases, retraction and stomal prolapse in 11 cases. The improvement of the quality of life was very satisfactory in 76%. CONCLUSIONS: Palliative surgery is widely practiced in digestive cancers. It improves the quality of life. African surgeons should be aware and well-educated to safely perform surgical palliative procedures.

[Extramammary myofibroblastoma affecting the pelvic region: a case report]. / Myofibroblastome extramammaire de localisation pelvienne: à propos d'un cas.

Mammary myofibroblastoma is a rare soft-tissue tumor. Extramammary myofibroblastomas are particularly rare. We here report the case of a 78-year-old man presenting with pelvic pain relieved by defecation or urination. Rectal examination showed a mass in front of the anterior rectal wall. The magnetic resonance imaging (MRI) showed a well-circumscribed and heterogeneous mass measuring 10 x 6 x 8cm located behind the bladder which was pushed forward in front of the rectosigmoid. Immunohistochemical analyses showed diffuse co-expression on CD34 cells and desmin, Rb expression on most cells, oestrogen receptor expression, intense and diffuse P16 expression and a ki67 proliferation index of 25%. The patient had no recurrence 8 months after radiotherapy followed by surgery. Breast myofibroblastoma is a rare and benign tumor. Recurrence is hardly observed after local treatment. This study highlights the supporting role of radiotherapy in the efficacy of surgery.

New Insights Into c.815_824dup Pathogenic Variant of BRCA1 in Inherited Breast Cancer: A Founder Mutation of West African Origin.

Founder mutations have been reported in BRCA1 and BCRA2 in different ethnic groups with inherited breast cancer. Testing of targeted mutations in specific populations is important for cancer prevention in mutation carriers. In Sub-Saharan Africa, only a few studies have reported specific founder mutations in inherited breast cancer. The pathogenic variant c.815_824dup of BRCA1 has been reported as the most frequent among African American populations with inherited breast cancer and was supposed to have a West African origin. Recent report from Senegal identified this variant in women with inherited breast cancer at the highest frequency ever reported. The variant was linked to a common haplotype confirming its founder effect in West Africa. In this article, we review the mutation history of c.815_824dup and discuss how it spread out of Africa through the transatlantic slave trade.

Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After in vitro Irradiation.

Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry. Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0-4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations. Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10-17), centric rings (p = 4.0310-14), and resulting double-strand-breaks (DSB) (p = 1.32 10-18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa. Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.

Systematic screening for cervical cancer in Dakar region: prevalence and correlation with biological and socio-demographic parameters.

BACKGROUND: Cervical cancer is a major public health problem. In 2018, globally 569,847 cervical cancer were diagnosed and 311,000 deaths were projected due to this preventable disease. Worldwide, therefore, the cervical cancer disease ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women in 2018.The high rate of dysplasia in Senegal and the absence of well-organized screening programs informed this study, which aims to determine the prevalence of cervical dysplasia and its relationship to biological and socio-demographic characteristics. METHODS: This study is based on 1000 conventional smears collected during routine cervical cancer screening at the Gaspard Camara Health Center and the Histology - Embryology and Cytogenetics Laboratory of the Cheikh Anta DIOP University in Dakar. The smears were read according to the Bethesda and Richart systems. However, all data were returned to the Bethesda system using the correspondence table between the different classifications of squamous cell lesions of the cervix. Some of the patients with abnormal smears had colposcopy and if necessary a biopsy. Other patients with low-grade lesions were recommended to have their smears resumed in 6 months or 1 year later. RESULTS: Cytological analysis was performed for 1000 patients aged 16 to 82 years (mean age = 41 ± 11.16). Among these, 176 patients had abnormal smears, 23 had Atypical Squamous Cells of Undetermined Significance (ASCUS), 143 had a low-grade lesion, 9 had a high-grade lesion and 1 had carcinoma. Among the remaining 822 patients, cytological analysis revealed no suspected malignant lesions, but 623 among them had dystrophy and 2 were unsatisfactory. Among patients with abnormal smears, 104 patients (23 ASCUS + 71 low grade + 9 high grade + 1 carcinoma) had performed colposcopy, 40 of whom had normal colposcopy and 64 had abnormalities. Sixty-four (64) biopsies were performed. Four (4) were not satisfactory. However, for 26/60 biopsies, the histology was normal, 21/60 had a low grade, 11 displayed a high grade and only 2 had carcinoma. Among the 176 patients with abnormal smears, 72 low-grade patients had undergone cytological examination 6 months to 1 year later to determine the persistence, regression or progression of low-grade dysplasia. During follow-up, persistence was observed in 25% (n = 18) of cases, progression to High-grade squamous intraepithelial lesion (HSIL) was detected in 2.78% (n = 2), while 72.22% (n = 52) of the patients experienced regression. CONCLUSION: In this study, the prevalence of abnormal smear was 17.60% for cytology. Meanwhile, the Colposcopy and histology confirmed just 3.40%. These results underline the interest and need for a review of the discrepancies observed between pathologists.

The Association of Molecular Biomarkers in the Diagnosis of Cervical Pre-Cancer and Cancer and Risk Factors in Senegalese.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although recent studies have suggested that p16INK4a may be a useful surrogate biomarker of cervical neoplasia, Ki-67 and human papillomavirus testing have also been shown to be useful in detecting neoplasia. The purpose of this study was to determine the expression of p16INK4a and Ki-67 in cervical neoplasia and its correlations with cofactors. METHODS: The study involved 69 patients with and without cervical neoplasia who underwent colposcopic directed biopsy. On each patient, two samples were taken; the first was used for immunohistochemistry and the second for molecular testing, using HPV16and18 genotyping Real-Time PCR Kit. RESULTS: The study revealed the expression level of p16INK4a and Ki-67 in a descending order, from invasive squamous cell carcinoma (SCC), CIN2/3, CIN1 and non-dysplastic lesions. Correlations showed an association between the staining of p16NK4a and Ki-67 with the increase of age (OR: 1.79 (95%IC: 0.49 - 6.55), p = 0.037) and marital status (OR: 0.17 (95%IC: 0.04 - 0.68), p = 0.003). We found that the expressions of p16INK4a and Ki-67 were significantly different between invasive SCC vs non-dysplasia (OR: 44.57 (95%IC: 4.91 - 403.91), p <0.0001). The study showed significant correlation between HPV 16and18 infection with p16 INK4a and Ki-67 expression (OR: 0.13 (95%IC: 0.03 - 0.52), p <0.0001). Strong expression of p16INK4a and Ki-67 were observed in invasive squamous cell carcinoma, moderate staining was found in CIN2/3, weak staining in CIN1 and normal histology. CONCLUSION: Our findings indicate that p16INK4a and Ki-67 expressions associated strongly with cervical pathology. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal.

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.

Somatic Mitochondrial Mutations in Oral Cavity Cancers among Senegalese Patients.

Background: Somatic mutations affecting the mitochondrial DNA (mtDNA) have been frequently observed in human cancers and proposed as important oncological biomarkers. However, the exact mtDNA mutations that is responsible for the pathogenesis of cancer remains unclear. The aim of this study was to investigate somatic mutations in the MT-CYB and D-Loop regions of mitochondrial DNA (mtDNA) in oral cavity cancers from Senegalese patients. Methods: MT-CYB and the D-Loop of mtDNA derived from 45 oral cavity cancer tissues and 21 control blood samples were assessed by PCR and sequencing. The sequences of MT-CYB and the D-Loop from cancerous tissues were compared with control sequences, and sequence differences were recognized as somatic mutations. Results: Overall, 389 somatic mtDNA mutations were identified, most of which (79.43%) were located in the D-Loop region. The majority of base substitution mutations were G-to-A (63.93%) and T-to-C (16.39%) transitions. In the protein-coding MT-CYB gene, 29 missense mutations were observed. The pathogenic mutation load of MT-CYB was 3.11%. Pathogenic mutations were carried by 25% of patients. pArg76Pro (pArg282Pro in rCRS) was novel and was the most common pathogenic mutation observed. Conclusion: These results strongly indicate that mtDNA mutations are a potential marker of oral cavity cancer.

[Cancer of the vulva: Diagnostic stages, treatment and survival in a country with limited resources (Burkina Faso)]. / Cancer de la vulve : stades diagnostiques, traitement et survie dans un pays aux ressources limitées (Burkina Faso).

INTRODUCTION: Vulvar cancer is rare and belatedly diagnosed in Africa. We describe its diagnostic stages, therapeutic and evolution features in a country with limited resources. METHODOLOGY: Forty-seven cases of vulvar cancer diagnosed between 2013 and 2018 in Burkina Faso, were analyzed retrospectively. The diagnostic stages, therapeutic and evolution terms were considered. Survival was calculated through the Kaplan Meier Method and compared using the Logrank technique. RESULTS: Stages IA and IB accounted for 10.6%. Radiotherapy was not available and chemotherapy was done in 9 cases. Full vulvectomy with bilateral inguino-femoral dissection was performed in 11 cases. Average survival was 41 months with a median of 52 months. The difference in survival according to the diagnostic stages were highly significant statistically (P=0.000). DISCUSSION: Cancer of the vulva is rare and raises major therapeutic difficulties in countries with limited resources. Surgery is the only affordable weapon. Evolution would be better if radiochemotherapy was possible. CONCLUSION: Radiochemotherapy cannot be done due to the lack of a radiotherapy unit and the high cost of cytotoxics. Surgery is largely palliative and/or mutilating. Survival is modest. An early diagnosis could help promote conserving treatments.

Biological Dosimetry Network in Africa: Establishment of a Dose-Response Curve Using Telomere and Centromere Staining.

PURPOSE: Biological dosimetry, based on the relationship between the absorbed dose after exposure to ionizing radiation and the frequency of scored aberrations, has been and continues to be an important tool for estimating the dose after exposure. Dicentric chromosomes are considered to be the most specific and sensitive aberration related to radiation exposure. Here, we established the dose-response curve following in vitro irradiation of circulating lymphocytes from healthy donors from three African countries after scoring unstable chromosomal aberrations. MATERIALS AND METHODS: Blood samples from 16 African donors were exposed to various doses (0 to 4 Gy) using an X-RAD320 x-ray system with a maximum photon energy of 250 kV at a dose rate of 0.1 Gy min. Blood lymphocytes were cultured for 48 h, and chromosomal aberrations were scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined. RESULTS: No dicentric chromosomes were found after the analysis of 2,669 first-division metaphases before in vitro exposure. We established a linear-quadratic dose-response curve based on the frequency of dicentric and ring chromosomes and calculated double-strand breaks, taking into account all scored aberrations. CONCLUSION: The generation of a specific dose-response curve for African donors will allow the practice of precise biological dosimetry in these countries. This work is the first step towards realizing an African biodosimetry network and the establishment of a biological dosimetry laboratory, which could play a major role in the application of radioprotection norms.