Disparities in breast cancer mortality among Latin American women: trends and predictions for 2030.

BACKGROUND: Breast cancer is among the leading cause of cancer-related mortality among Latin American and Caribbean (LAC) women, but a comprehensive and updated analysis of mortality trends is lacking. The objective of this study was to determine the breast cancer mortality rates between 1997 and 2017 for LAC countries and predict mortality until 2030. METHODS: We retrieved breast cancer deaths across 17 LAC countries from the World Health Organization mortality database. Age-standardized mortality rates per 100,000 women-years were estimated. Mortality trends were evaluated with Joinpoint regression analyses by country and age group (all ages, < 50 years, and ≥ 50 years). By 2030, we predict number of deaths, mortality rates, changes in population structure and size, and the risk of death from breast cancer. RESULTS: Argentina, Uruguay, and Venezuela reported the highest mortality rates throughout the study period. Guatemala, El Salvador, and Nicaragua reported the largest increases (from 2.4 to 2.8% annually), whereas Argentina, Chile, and Uruguay reported downward trends (from - 1.0 to - 1.6% annually). In women < 50y, six countries presented downward trends and five countries showed increasing trends. In women ≥ 50y, three countries had decreased trends and ten showed increased trends. In 2030, increases in mortality are expected in the LAC region, mainly in Guatemala (+ 63.0%), Nicaragua (+ 47.3), El Salvador (+ 46.2%), Ecuador (+ 38.5%) and Venezuela (+ 29.9%). CONCLUSION: Our findings suggest considerable differences in breast cancer mortality across LAC countries by age group. To achieve the 2030 sustainable developmental goals, LAC countries should implement public health strategies to reduce mortality by breast cancer.

The role of daughters in relation to their mother's cervical cancer diagnosis and treatment in Guatemala: a descriptive study.

PURPOSE: There is currently no information on how caregivers for women diagnosed with cervical cancer in Guatemala, particularly daughters, are affected by their supportive role. This study's objective was to describe the support role of caregivers in the country, with a focus on daughters with a mother diagnosed with cervical cancer. METHODS: This analysis utilizes data from a cross-sectional study which aimed to understand pathways to cervical cancer care. Women seeking cervical cancer treatment at the Instituto de Cancerologia (INCAN) in Guatemala City, Guatemala and their companions were surveyed. Descriptive statistics were calculated. RESULTS: One hundred forty-five women seeking treatment and 71 companions participated in the study. Patient's daughters were most frequently reported as the person who provided the most support (51%) and as the most reported to have encouraged the patient to seek care. Furthermore, daughters were noted as the person most reported to fulfill the major household and livelihood roles of the patient while they were seeking or receiving treatment (38.0%). Most daughters reported that they were missing housework (77%), childcare (63%), and income-earning activities (60%) to attend the appointment with their mothers. CONCLUSION: Our study suggests that in Guatemala cervical cancer patient's daughters have a significant support role in their mother's cancer diagnosis. Furthermore, we found that while caring for their mothers, daughters in Guatemala are often unable to participate in their primary labor activities. This highlights the additional burden that cervical cancer has on women in Latin America.

Mycoplasma genitalium prevalence, antimicrobial resistance-associated mutations, and coinfections with non-viral sexually transmitted infections in high-risk populations in Guatemala, Malta, Morocco, Peru and South Africa, 2019-2021.

The prevalence of Mycoplasma genitalium (MG) and MG antimicrobial resistance (AMR) appear to be high internationally, however, prevalence data remain lacking globally. We evaluated the prevalence of MG and MG AMR-associated mutations in men who have sex with men (MSM) in Malta and Peru and women at-risk for sexually transmitted infections in Guatemala, South Africa, and Morocco; five countries in four WHO regions mostly lacking MG prevalence and AMR data, and estimated MG coinfections with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Male urine and anorectal samples, and vaginal samples were tested for MG, CT, NG, and TV (only vaginal samples) using Aptima assays (Hologic). AMR-associated mutations in the MG 23S rRNA gene and parC gene were identified using ResistancePlus MG kit (SpeeDx) or Sanger sequencing. In total, 1,425 MSM and 1,398 women at-risk were recruited. MG was detected in 14.7% of MSM (10.0% in Malta and 20.0% Peru) and in 19.1% of women at-risk (12.4% in Guatemala, 16.0% Morocco, 22.1% South Africa). The prevalence of 23S rRNA and parC mutations among MSM was 68.1 and 29.0% (Malta), and 65.9 and 5.6% (Peru), respectively. Among women at-risk, 23S rRNA and parC mutations were revealed in 4.8 and 0% (Guatemala), 11.6 and 6.7% (Morocco), and 2.4 and 3.7% (South Africa), respectively. CT was the most frequent single coinfection with MG (in 2.6% of MSM and 4.5% of women at-risk), compared to NG + MG found in 1.3 and 1.0%, respectively, and TV + MG detected in 2.8% of women at-risk. In conclusion, MG is prevalent worldwide and enhanced aetiological MG diagnosis, linked to clinical routine detection of 23S rRNA mutations, in symptomatic patients should be implemented, where feasible. Surveillance of MG AMR and treatment outcome would be exceedingly valuable, nationally and internationally. High levels of AMR in MSM support avoiding screening for and treatment of MG in asymptomatic MSM and general population. Ultimately, novel therapeutic antimicrobials and/or strategies, such as resistance-guided sequential therapy, and ideally an effective MG vaccine are essential.

Cervical cancer knowledge and barriers and facilitators to screening among women in two rural communities in Guatemala: a qualitative study.

BACKGROUND: Approximately 80% of deaths due to cervical cancer occur in low- and middle-income countries. In Guatemala, limited access to effective screening and treatment has resulted in alarmingly high cervical cancer incidence and mortality rates. Despite access to free-of-cost screening, women continue to face significant barriers in obtaining screening for cervical cancer. METHODS: In-depth interviews (N = 21) were conducted among women in two rural communities in Guatemala. Interviews followed a semi-structured guide to explore knowledge related to cervical cancer and barriers and facilitators to cervical cancer screening. RESULTS: Cervical cancer knowledge was variable across sites and across women. Women reported barriers to screening including ancillary costs, control by male partners, poor provider communication and systems-level resource constraints. Facilitators to screening included a desire to know one's own health status, conversations with other women, including community health workers, and extra-governmental health campaigns. CONCLUSIONS: Findings speak to the many challenges women face in obtaining screening for cervical cancer in their communities as well as existing facilitators. Future interventions must focus on improving cervical cancer-related knowledge as well as mitigating barriers and leveraging facilitators to promote screening.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

OBJECTIVE: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. MATERIALS AND METHODS: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. RESULTS: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. CONCLUSION: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Liver cancer mortality in Mexico: trend analysis from 1998 to 2018.

OBJECTIVE: To examine overall, sex, and state-specific liver cancer mortality trends in Mexico. Materials and meth-ods. Joinpoint regression was used to examine the trends in age-standardized mortality rates of liver cancer between 1998-2018. Estimated annual percent change with 95% confi-dence intervals (95%CI) were computed. Age-period-cohort models were used to assess the effects of age, calendar year, and birth cohort. RESULTS: The state-specific mortality rates ranged from 3.34 (Aguascalientes) to 7.96 (Chiapas) per 100 000 person-years. Sex-specific rates were roughly equal, nationwide. Overall, we observed a statistically significant decrease in liver cancer mortality rates between 1998-2018 (annual percent change, -0.8%; 95%CI -1.0, -0.6). The overall age-period-cohort models suggest that birth cohort may be the most important factor driving the trends. CONCLUSIONS: While there was overall decline in liver cancer mortality, differences in rates by region were observed. The regional differences may inform future studies of liver cancer etiology across the country.

Circulating bile acid concentrations and non-alcoholic fatty liver disease in Guatemala.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. AIMS: To characterise the relationship between bile acid levels and NAFLD at the population level METHODS: We conducted a cross-sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC-MS/MS. Adjusted prevalence odds ratios (PORadj ) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. RESULTS: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1  = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1  = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1  = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1  = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1  = 1.81). CONCLUSIONS: The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids.

Associations between aflatoxin B1-albumin adduct levels with metabolic conditions in Guatemala: A cross-sectional study.

BACKGROUND AND AIMS: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. METHODS: Four-hundred twenty-three individuals were included in the study, in which AFB1-albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1-albumin adduct levels categorized into quartiles. RESULTS: The study found a significant association between AFB1-albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71-8.19; P-trend .003). No associations were observed between AFB1-albumin adduct levels and the other conditions. CONCLUSIONS: As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms.

Liver cancer mortality in Mexico: trend analysis from 1998 to 2018 / Mortalidad por cáncer hepático en México: análisis de tendencias de 1998 a 2018

Abstract: Objective: To examine overall, sex, and state-specific liver cancer mortality trends in Mexico. Materials and methods: Joinpoint regression was used to examine the trends in age-standardized mortality rates of liver cancer between 1998-2018. Estimated annual percent change with 95% confidence intervals (95%CI) were computed. Age-period-cohort models were used to assess the effects of age, calendar year, and birth cohort. Results: The state-specific mortality rates ranged from 3.34 (Aguascalientes) to 7.96 (Chiapas) per 100 000 person-years. Sex-specific rates were roughly equal, nationwide. Overall, we observed a statistically significant decrease in liver cancer mortality rates between 1998-2018 (annual percent change, -0.8%; 95%CI -1.0, -0.6). The overall age-period-cohort models suggest that birth cohort may be the most important factor driving the trends. Conclusions: While there was overall decline in liver cancer mortality, differences in rates by region were observed. The regional differences may inform future studies of liver cancer etiology across the country.

Resumen: Objetivo: Examinar la tendencia general, por sexo y estado, de mortalidad por cáncer hepático en México. Material y métodos: Se utilizó regresión joinpoint para examinar las tendencias en las tasas de mortalidad estandarizadas por edad de cáncer hepático (1998-2018). Se estimó el cambio porcentual anual con intervalos de confianza al 95% (IC95%). Se usaron modelos de edad-periodo-cohorte para evaluar el efecto de edad, año calendario y cohorte de nacimiento. Resultados: La mortalidad osciló entre 3.34 (Aguascalientes) y 7.96 (Chiapas) por 100 000 años-persona. La mortalidad por sexo fue relativamente similar a nivel nacional. La mortalidad general disminuyó entre 1998-2018 (cambio porcentual anual, -0.8%; IC95% -1.0, -0.6). La cohorte de nacimiento parece ser el factor más importante que afecta las tendencias. Conclusiones: A pesar de la disminución de mortalidad por cáncer hepático, se observó variación regional en las tasas. Estas diferencias podrían informar estudios futuros sobre la etiología de cáncer hepático en México.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico / Niveles de aflatoxina y prevalencia de mutaciones del gen TP53 por aflatoxina en carcinoma hepatocelular en México

Abstract: Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. Materials and methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. Results: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. Conclusion: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Resumen: Objetivo: Determinar la exposición a aflatoxina_B1 (AFB1) en el sur de México y la presencia de la mutación característica de AFB1 en tejido de carcinoma hepatocelular (CHC) de pacientes de un centro oncológico. Material y métodos: Se estimó la prevalencia y distribución de AFB1 en una muestra representativa de 100 mujeres y hombres de Chiapas a partir de la Encuesta Nacional de Salud y Nutrición 2018-19. También se observó la presencia de la mutación característica de AFB1 en el codón 249 (R249S), y otras mutaciones relevantes del gen TP53 en bloques de tejido de CHC de 24 mujeres y 26 hombres estudiados en un centro de referencia nacional de oncología. Resultados: La prevalencia de AFB1 en las muestras de suero fue de 85.5% (IC95% 72.1-93.1) y la mediana de la concentración 0.117 pg/µL (IQR, 0.050-0.350). Se detectó TP53 R249S en tres de 50 casos de CHC (6.0%) y se observaron cuatro transversiones G>T potencialmente inducidas por AFB1. Conclusión: El presente análisis proporciona evidencia de que la AFB1 puede tener un papel relevante en la etiología del CHC en México.

Cervical cancer mortality among young women in Latin America and the Caribbean: trend analysis from 1997 to 2030.

BACKGROUND: Cervical cancer continues to show a high burden among young women worldwide, particularly in low- and middle-income countries. Limited data is available describing cervical cancer mortality among young women in Latin America and the Caribbean (LAC). The purpose of this study was to examine the mortality trends of cervical cancer among young women in LAC and predict mortality rates to 2030. METHODS: Deaths from cervical cancer were obtained from the World Health Organization mortality database. Age-standardized mortality rates per 100,000 women-years were estimated in women aged 20-44 years using the world standard population for 16 countries (and territories) in LAC from 1997 to 2017. We estimated the average mortality rates for the last 4 years (2014-2017). Joinpoint regression models were used to identify significant changes in mortality trends. Nordpred method was used for the prediction of the mortality rates to 2030. RESULTS: Between 2014 and 2017, Paraguay and Venezuela had the highest mortality rates of cervical cancer, whereas Puerto Rico had the lowest rates. Overall, most of the LAC countries showed downward trends of cervical cancer mortality over the entire period. Significant decreases were observed in Chile (Average annual percent change [AAPC]: - 2.4%), Colombia (AAPC: - 2.0%), Cuba (AAPC: - 3.6%), El Salvador (AAPC: - 3.1%), Mexico (AAPC: - 3.9%), Nicaragua (AAPC: - 1.7%), Panama (AAPC: - 1.7%), and Peru (AAPC: - 2.2%). In contrast, Brazil (AAPC: + 0.8%) and Paraguay (AAPC: + 3.7%) showed significant upward trends. By 2030, mortality rates are not predicted to further decrease in some LAC countries, including Argentina, Paraguay, and Venezuela. CONCLUSIONS: Mortality trends of cervical cancer among young women have large variability in LAC countries. Cervical cancer screening programs have a high priority for the region. Primary and secondary prevention in the community are necessary to accelerate a reduction of cervical cancer mortality by 2030.

Sex and age differences in mortality trends of gastric cancer among Hispanic/Latino populations in the United States, Latin America, and the Caribbean.

Background: An up-to-date analysis of gastric cancer mortality among Hispanic/Latino populations is required for estimating disease burden and assessing the effectiveness of clinical and preventive strategies. Methods: We retrieved gastric cancer deaths between 1997 and 2017 (as available) from the Surveillance, Epidemiology, and End Results Program (United States Hispanics) and the World Health Organization databases (Puerto Rico, 16 Latin American and Caribbean countries). Joinpoint regression analysis was used to examine trends in age-standardized mortality rates (ASMR; per 100 000 person-years) and calculate average annual percent changes (AAPCs) by country (or territory), age group (25-49 and ≥50 years), and sex. Trends were compared to assess slope parallelism. Findings: In 2017, Chile (31·8), Colombia (24·3) and Costa Rica (24·3) had the highest ASMR of gastric cancer for men, while Guatemala (17·2), Peru (13·5), and Costa Rica (13·3) had the highest ASMR for women. Small-to-moderate mortality declines (AAPCs ranged -4 to -0.5%) were observed between 1997 and 2017. In almost all countries, trends decreased among individuals aged ≥50 years. However, age-specific trends were not parallel (p-values <0.05) in Brazil, Colombia, Mexico, the United States, and Venezuela for both men and women, and in five additional countries for only women; with a few countries showing stable or slightly increasing trends for individuals aged 25-49 years. Interpretation: Overall gastric cancer mortality rates in Hispanics/Latinos declined in the last two decades. However, there was a notable variation in trends by country, sex, and age group. Continued and targeted prevention efforts are needed to reduce the disease burden in these vulnerable populations. Funding: Universidad Cientifica del Sur, Peru, and National Cancer Institute, United States.

Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer.

PURPOSE: Mutations in hereditary breast cancer genes play an important role in the risk for cancer. METHODS: Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. RESULTS: A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). CONCLUSIONS: Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

Cervical cancer mortality in Peru: regional trend analysis from 2008-2017.

BACKGROUND: Cervical cancer is the third leading cause of cancer-related death among Latin American women. Peru has the sixth highest mortality rate for cervical cancer in the region with regional variations. We aimed to determine overall and regional cervical cancer mortality rates and trends in Peru between 2008 and 2017. METHODS: We performed an ecological study on the number of deaths by cervical cancer in Peru. Deaths were extracted from the Peruvian Ministry of Health mortality database. Age-standardized mortality rates (ASMR) were estimated per 100,000 women-years using the world standard Segi population. We computed mortality trends using the Joinpoint regression program, estimating the annual percent change (APC). For spatial analysis, GeoDA software was used. RESULTS: Peru showed downward trends in the last decade (from 11.62 in 2008 to 9.69 in 2017 (APC = - 2.2, 95% CI: - 4.3, - 0.1, p < 0.05). According to regional-specific analysis, the highest ASMR was in the rainforest region, although this declined from 34.16 in 2008 to 17.98 in 2017 (APC = - 4.3, 95% CI: - 7.2, - 1.3, p < 0.01). Concerning spatial analysis and clustering, the mortality rates from 2008 to 2017 showed a positive spatial autocorrelation and significant clustering (Moran's I: 0.35, p < 0.001) predominantly in the neighboring North-East departments (Loreto, Ucayali, and San Martin). CONCLUSIONS: Although mortality trends in the entire population are decreasing, mortality rates remain very high, mainly in the rainforest region. Our results encourage a need for further development and improvement of the current health care delivery system in Peru.