2 research outputs found
Absence of Germline BRCA1 c.68_69delAG and c.5266dupC Mutations among Hormone Receptor-negative Breast Cancer Patients: A First Impression at a Tertiary Cancer-care Facility in Tanzania
The germline BRCA1 c.68_69delAG (185delAG) and c.5266dupC (5382insC) mutations are associated with hormone receptor-negative breast cancer (BC). Limited studies have examined their contribution to alarming BC incidence in Sub Saharan Africa (SSA). Our study aimed to examine the contribution of germline BRCA1 c.68_69delAG and c.5266dupC mutations to BC incidence among hormone receptor-negative BC patients admitted to Ocean Road Cancer Institute in Tanzania. Face-to-face interviews were conducted to capture socio-demographic characteristics, anthropometric measurements, family history of cancer and reproductive information from each patient. Their histopathological data were extracted from the hospital medical records. The germline BRCA1 founder mutations were analyzed on blood samples using Sanger sequencing technology. The patients mean age at diagnosis was 47.05 ± 12.82 years. A family history of cancer was observed in 13.6% of patients. The germline BRCA1 c.68_69delAG and c.5266dupC mutations were not detected in the study group. Our findings indicate that the germline BRCA1 c.68_69delAG and c.5266dupC mutations do not contribute to BC manifestation in hormone receptor-negative BC patients in Tanzania. Thus, screening BC patients for these mutations has no clinical relevance. Our data further suggest that the c.68_69delAG and the c.5266dupC mutations should not be considered when developing genetic testing guidelines in Tanzania.
Keywords: Breast cancer, germline BRCA1 mutation, c.68_69delAG (185delAG), c.5266dupC (5382insC), Tanzani
The interplay between XPGâAsp1104His polymorphism and reproductive risk factors elevates risk of breast cancer in Tanzanian women: A multiple interaction analysis
Abstract Background Reproductive history and genetics are wellâknown risk factors of breast cancer (BC). Little is known about how these factors interact to effect BC. This study investigated the association of ten polymorphisms in DNA repair genes with BC susceptibility in the Tanzanian samples and further analyzed the association between reproductive risk factors and disease risk Methods A hospitalâbased caseâcontrol study in 263 histopathological confirmed BC patients and 250 ageâmatched cancerâfree controls was carried out. Allelic, genotypic, and haplotype association analyses were executed. Also, multifactor dimensionality reduction (MDR), and interaction dendrogram approaches were performed. Results The frequency of genotypic and allelic variants of XRCC1âArg399Gln (rs25487), XRCC2âArg188His (rs3218536), XRCC3âThr241Met (rs861539), XPGâAsp1104His (rs17655), and MSH2âGly322Asp (rs4987188) were significantly different between the groups (pâ<â0.05). Moreover, XRCC1âArg399Gln (rs25487), XRCC3âThr241Met (rs861539), and XPGâAsp1104His (rs17655) were associated with the increased risk of BC in coâdominant, dominant, recessive, and additive geneticâinheritance models (pâ<â0.05). XRCC1âArg/Gln genotype indicated a 3.1âfold increased risk of BC in preâmenopausal patients (p = 0.001) while XPGâHis/His genotype showed a 1.2âfold increased risk in younger BC patients (<40âyears) (p = 0.028). Asp/His+His/His genotypes indicated a 1.3âfold increased risk of BC in PR+ patients and a 1.1âfold decreased risk of BC in luminalâA patients (p = 0.014, p = 0.020, respectively). MDR analysis revealed a positive interaction between BC and the XPGâAsp1104His (rs17655) together with family history of cancer in the firstâdegree relatives. Dendrogram analysis indicated that the XPGâAsp1104His (rs17655) and family history of cancer in firstâdegree relatives were significantly synergistic and might be associated with an elevated risk of BC in Tanzania. Conclusions The XPGâAsp1104His (rs17655) might exert both independent and interactive effects on BC development in the Tanzanian women