Examinando por Autor "Bazo-Alvarez, Juan Carlos"

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Genetic Characterization in High-Risk Individuals from a Low-Resource City of Peru
(MDPI, 2022-11-15) Zavaleta, Elizabeth; Solis, Nelly; Palacios, Maria Isabel; Zevallos-Escobar, Liz Elva; Vasquez Corales, Edison; Bazo-Alvarez, Juan Carlos; Dominguez-Barrera, Constantino; Campos, Anthony; Wernhoff, Patrik; Ekstrøm, Per Olaf; Møller, Pål; Visnovska, Tina; Hovig, Eivind; Balazar-Palacios, Janina; Alvarez-Valenzuela, Karin; Nakken, Sigve; Dominguez-Valentin, Mev
Background: Genetic testing for hereditary cancers is inconsistently applied within the healthcare systems in Latin America. In Peru, the prevalence and spectrum of cancer-predisposing germline variants is thus poorly characterized. Purpose: To determine the spectrum and prevalence of cancer-predisposing germline variants and variants of uncertain significance (VUS) in high-risk individuals located in a Peruvian low-resource setting city. Methods: Individuals presenting clinical criteria for hereditary cancer syndromes or being unaffected with familial history of cancer were included in the study. Samples from a total of 84 individuals were subjected to a high-throughput DNA sequencing assay that targeted a panel of 94 cancer predisposition genes. The pathogenicity of detected germline variants was classified according to the established American College of Medical Genetics and Genomics (ACMG) criteria. All pathogenic variants were validated by cycling temperature capillary electrophoresis. Results: We identified a total of eight pathogenic variants, found in 19 out of 84 individuals (23%). Pathogenic variants were identified in 24% (10/42) of unaffected individuals with family history of cancer and in 21% (9/42) of individuals with a cancer diagnosis. Pathogenic variants were identified in eight genes: RET (3), BRCA1 (3), SBDS (2), SBDS/MLH1 (4), MLH1 (4), TP53 (1), FANCD2 (1), DDB2/FANCG (1). In cancer cases, all colon cancer cases were affected by pathogenic variants in MLH1 and SBDS genes, while 20% (2/10) of the thyroid cancer cases by RET c.1900T>C variants were affected. One patient with endometrial cancer (1/3) had a double heterozygous pathogenic variant in DDB2 and FANCG genes, while one breast cancer patient (1/14) had a pathogenic variant in TP53 gene. Overall, each individual presented at least 17 VUS, totaling 1926 VUS for the full study population. Conclusion: We describe the first genetic characterization in a low-resource setting population where genetic testing is not yet implemented. We identified multiple pathogenic germline variants in clinically actionable predisposition genes, that have an impact on providing an appropriate genetic counselling and clinical management for individuals and their relatives who carry these variants. We also reported a high number of VUS, which may indicate variants specific for this population and may require a determination of their clinical significance.
Acceso abierto
Genetic Characterization in High-Risk Individuals from a Low-Resource City of Peru
(MDPI, 2022-11-15) Zavaleta, Elizabeth; Solis, Nelly; Palacios, Maria Isabel; Zevallos-Escobar, Liz Elva; Vasquez Corales, Edison; Bazo-Alvarez, Juan Carlos; Dominguez-Barrera, Constantino; Campos, Anthony; Wernhoff, Patrik; Ekstrøm, Per Olaf; Møller, Pål; Visnovska, Tina; Hovig, Eivind; Balazar-Palacios, Janina; Alvarez-Valenzuela, Karin; Nakken, Sigve; Dominguez-Valentin, Mev
Background: Genetic testing for hereditary cancers is inconsistently applied within the healthcare systems in Latin America. In Peru, the prevalence and spectrum of cancer-predisposing germline variants is thus poorly characterized. Purpose: To determine the spectrum and prevalence of cancer-predisposing germline variants and variants of uncertain significance (VUS) in high-risk individuals located in a Peruvian low-resource setting city. Methods: Individuals presenting clinical criteria for hereditary cancer syndromes or being unaffected with familial history of cancer were included in the study. Samples from a total of 84 individuals were subjected to a high-throughput DNA sequencing assay that targeted a panel of 94 cancer predisposition genes. The pathogenicity of detected germline variants was classified according to the established American College of Medical Genetics and Genomics (ACMG) criteria. All pathogenic variants were validated by cycling temperature capillary electrophoresis. Results: We identified a total of eight pathogenic variants, found in 19 out of 84 individuals (23%). Pathogenic variants were identified in 24% (10/42) of unaffected individuals with family history of cancer and in 21% (9/42) of individuals with a cancer diagnosis. Pathogenic variants were identified in eight genes: RET (3), BRCA1 (3), SBDS (2), SBDS/MLH1 (4), MLH1 (4), TP53 (1), FANCD2 (1), DDB2/FANCG (1). In cancer cases, all colon cancer cases were affected by pathogenic variants in MLH1 and SBDS genes, while 20% (2/10) of the thyroid cancer cases by RET c.1900T>C variants were affected. One patient with endometrial cancer (1/3) had a double heterozygous pathogenic variant in DDB2 and FANCG genes, while one breast cancer patient (1/14) had a pathogenic variant in TP53 gene. Overall, each individual presented at least 17 VUS, totaling 1926 VUS for the full study population. Conclusion: We describe the first genetic characterization in a low-resource setting population where genetic testing is not yet implemented. We identified multiple pathogenic germline variants in clinically actionable predisposition genes, that have an impact on providing an appropriate genetic counselling and clinical management for individuals and their relatives who carry these variants. We also reported a high number of VUS, which may indicate variants specific for this population and may require a determination of their clinical significance.
Acceso abierto
“Mental health among the sugarcane industry farmers and non-farmers in Peru: a cross-sectional study on occupational health“
(BMJ Publishing Group, 2022-10-20) Bazo-Alvarez, Juan Carlos; Bazalar-Palacios, Janina; Bazalar, Jahaira; Flores, Elaine C
“Objective Describe the occupational characteristics of farmer and non-farmer workers and investigate critical occupational risk factors for mental disorders in sugarcane farmers in Peru. Method We conducted a cross-sectional study with occupational health and safety focus among farmers and non-farmers. Mental disorder symptoms were evaluated through the local validated version of the 12-Item General Health Questionnaire (GHQ-12). We explored the association between mental disorder symptoms, work conditions and known occupational risk factors (weekly working hours, pesticide exposures, heat stress and heavy workload). Negative binomial regression models were fitted, and 95% CIs were calculated. Results We assessed 281 workers between December 2019 and February 2020. One hundred and six (37.7%) respondents identified themselves as farmworkers. The mean GHQ-12 scores for farmers and non-farmers were 3.1 and 1.3, respectively. In the fully adjusted multivariable model, mental disorder symptom counts among farmers were more than twice as high as those of non-farmers (β: 2.11; 95%CI: 1.48 to 3.01). The heavy workload increased the mean number of mental disorder symptoms by 68% (95% CI: 21% to 133%), and each additional working hour per day increased the mean number of mental disorder symptoms by 13% (95% CI: 1% to 25%). Conclusion Farmers have higher mental disorder symptoms than non-farmers. A heavy workload and more working hours per day are independently associated with more mental disorder symptoms. Our findings highlight the importance of including mental health within occupational programmes and early interventions tailored to sugarcane industrial mill workers in the Latin American context.“
Acceso abierto
“Mental health among the sugarcane industry farmers and non-farmers in Peru: a cross-sectional study on occupational health“
(BMJ Publishing Group, 2022-10-20) Bazo-Alvarez, Juan Carlos; Bazalar-Palacios, Janina; Bazalar, Jahaira; Flores, Elaine C
“Objective Describe the occupational characteristics of farmer and non-farmer workers and investigate critical occupational risk factors for mental disorders in sugarcane farmers in Peru. Method We conducted a cross-sectional study with occupational health and safety focus among farmers and non-farmers. Mental disorder symptoms were evaluated through the local validated version of the 12-Item General Health Questionnaire (GHQ-12). We explored the association between mental disorder symptoms, work conditions and known occupational risk factors (weekly working hours, pesticide exposures, heat stress and heavy workload). Negative binomial regression models were fitted, and 95% CIs were calculated. Results We assessed 281 workers between December 2019 and February 2020. One hundred and six (37.7%) respondents identified themselves as farmworkers. The mean GHQ-12 scores for farmers and non-farmers were 3.1 and 1.3, respectively. In the fully adjusted multivariable model, mental disorder symptom counts among farmers were more than twice as high as those of non-farmers (β: 2.11; 95%CI: 1.48 to 3.01). The heavy workload increased the mean number of mental disorder symptoms by 68% (95% CI: 21% to 133%), and each additional working hour per day increased the mean number of mental disorder symptoms by 13% (95% CI: 1% to 25%). Conclusion Farmers have higher mental disorder symptoms than non-farmers. A heavy workload and more working hours per day are independently associated with more mental disorder symptoms. Our findings highlight the importance of including mental health within occupational programmes and early interventions tailored to sugarcane industrial mill workers in the Latin American context.“