ABSTRACT. Abnormalities in the breast cancer tumor suppressor genes (BRCA1 and BRCA2) are associated with breast and ovarian cancer. Recently, two single nucleotide polymorphisms (SNPs; rs11571836 and rs1799943) were identified, both located in untranslated regions of chromosome 13, associated with cardiovascular disease (CVD) in a multi-ethnic population. We examined the association between these BRCA2 polymorphisms and traits of CVD patients from Saudi Arabia. We genotyped rs11571836 and rs1799943 in 159 unrelated CVD patients and 176 healthy controls. The genotype and allele distributions in the overall population revealed a statistically significant association between rs1799943 and CVD (P = 0.01-0.022), whereas no risk association was identified for rs11571836. Additionally, haplotype analysis using both SNPs demonstrated no association between the SNPs and CVD. The genotype distribution of the 2 SNPs in the normal Saudi population deviated significantly (P < 0.000001) from that of the 6 different HapMap populations (CEU, CHB-Han, JPT, YRI, GIH, and MKK), except for the JPT population for rs1799943. This is the BRCA2 variants and cardiovascular disease first study to examine the association between these SNPs and CVD in a Saudi population. Our results suggest that the increased health risk associated with the rs11571836 genotype is specific to male patients suffering from CVD. Stratification of patients and controls based on gender revealed no association between rs1799943 and the risk of CVD in either gender. These SNPs should be evaluated in larger cohorts in different populations to determine their suitability as screening markers for predicting CVD risk earlier in life to implement necessary preventive measures.
e15522 Background: Taxanes are an integral part of chemotherapy for a broad range of tumor types. The usual toxicities associated with Taxane use are peripheral neuropathy, myelosuppression and musculoskeletal adverse effects. Very few studies have reported taxane induced pulmonary toxicity objectively. In our study we explored Taxane induced pulmonary toxicity based on discrete CT findings. Methods: 40 non-smokers diagnosed with Her-2 negative breast cancer who received Taxane monotherapy from 2017 to 2018 were retrospectively analyzed for pre and post therapy CT changes. Following CT findings were considered significant as pulmonary toxicity; (a) Nonspecific area with ground-glass attenuation, (b) multifocal areas of airspace consolidation, (c) patchy distribution of ground-glass attenuation accompanied by interlobular septal thickening and (d) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. The CT findings were assessed independently by two radiologists and one pulmonologist. Results: Our study showed that 5 patients (12.5%) developed pulmonary changes on chest CT post Taxane therapy as summarized in Table. Conclusions: Our study shows that taxane has more potential to induce pulmonary toxicity than reported in present literature. Given that taxanes are the most widely used chemotherapy, it is of utmost necessity to be cognizant of this under-reported potentially fatal adverse effect in a large population. Further studies should be conducted to better understand the true potential, mechanisms and patterns of taxanes induced pulmonary toxicity. [Table: see text]
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