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Copyright of International Journal of Medicine & Science of Physical Activity & Sport / Revista Internacional de Medicina y Ciencias de la Actividad Física y del Deporte is the property of Revista Internacional de Medicina y Ciencias de la Actividad Fisica y del Deporte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity., Methods: We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs. We also used the entire set of summary statistics to compute polygenic risk scores (PRSs) and carried out comparisons at the population and continental level., Results: We observed the strongest differences among continental regions for the five top SNPs in chromosome 3. European, American, and South Asian populations showed similar LD patterns. Average PRSs in South Asian and American populations were consistently higher than those observed in Europeans. While PRS distributions were similar among South Asians, the American populations showed striking differences among them., Conclusions: Considering the caveats of PRS transferability across ethnicities, our analysis showed that American populations present the highest genetic risk score, hence potentially higher propensity, for COVID-19 severity. Independent validation is warranted with additional summary statistics and phenotype data.

The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes ( PON1 , CAT , GSTP1 , FCGR3 , ATM , PIK3CA , HER3 , BARD1 , LDB2 , BRINP1 , chr6 intergenic region, RAB22A , TRPC6 , LINC01060 , EGFR , ABCB1 , and HER2 ). Tumor samples from 50 women with early breast cancer were genotyped using the iPlex ® Gold chemistry and MassARRAY platform, and patients were classified as good responders (Miller-Payne tumor grades 4-5) and poor responders (Miller-Payne tumor grades 1-3), as assessed upon surgery after 6 months of treatment. Proportions of patients with the HER2Ala1170Pro (rs1058808) SNP double mutation were higher in good (58.62%) than poor (20%) responders ( p = 0.025). Similarly, proportions of patients carrying the synonymous SNP rs2070096 ( BARD1Thr351= ) (wv + vv) were higher in patients showing a pathological complete response (46.67%) than in those not showing this response (15.15%) ( p = 0.031). The SNPs rs1058808 ( HER2Ala1170Pro ) and rs2070096 ( BARD1Thr351= ) were identified here as potential biomarkers of a good response to anti-HER2 treatment.

HER2-positive breast cancer (BC) is an aggressive subtype that affects 20-25% of BC patients. For these patients, neoadjuvant therapy is a good option that targets a pathological complete response (pCR) and more breast-conserving surgery. In effect, the outcomes of patients with HER2-positive BC have dramatically improved since the introduction of anti-HER2 antibodies such as trastuzumab (TZ) and/or pertuzumab (PZ) added to chemotherapy. This study sought to examine whether correlation exists between copy number variations (CNVs) in several genes related to the PI3K/AKT pathway ( HER2, FGFR1, PIK3CA, AKT3 and MDM2 ) and the efficacy of anti-HER2 neoadjuvant treatment in patients with early HER2-positive BC. Forty-nine patients received TZ or PZ/TZ and chemotherapy as neoadjuvant treatment. Gene CNVs were determined by quantitative polymerase chain reaction on paraffin-embedded biopsy specimens. The response to 6 months of therapy was assessed by Miller-Payne grading of the tumor on surgical resection; grades 4 and 5, indicating >90% tumor reduction, were defined as a good response. A good response was shown by 64.5% and a pCR by 31.2% of patients. When stratified by anti-HER2 antibody received and gene CNV, it was found that patients with FGFR1 gene amplification or those with FGFR1 amplification treated with TZ alone showed a poor response ( p = 0.024 and p = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing FGFR1 amplification ( p = 0.021). Although based on a small sample size, our findings suggest that patients with FGFR1 amplification might benefit less from anti-HER2 antibody therapy.