Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017)
Abstract Background and aims Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevale...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-06-01
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| Series: | Health Science Reports |
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| Online Access: | https://doi.org/10.1002/hsr2.155 |
| _version_ | 1818848802047524864 |
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| author | Christian S. Alvarez Jeremy Ortiz Giovanna Bendfeldt‐Avila Yi Xie Mingyi Wang Dongjing Wu Herbert Higson Elisa Lee Kedest Teshome Joaquin Barnoya David E. Kleiner John D. Groopman Roberto Orozco Katherine A. McGlynn Eduardo Gharzouzi Michael Dean |
| author_facet | Christian S. Alvarez Jeremy Ortiz Giovanna Bendfeldt‐Avila Yi Xie Mingyi Wang Dongjing Wu Herbert Higson Elisa Lee Kedest Teshome Joaquin Barnoya David E. Kleiner John D. Groopman Roberto Orozco Katherine A. McGlynn Eduardo Gharzouzi Michael Dean |
| author_sort | Christian S. Alvarez |
| collection | DOAJ |
| description | Abstract Background and aims Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1‐signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. Methods Formalin‐fixed, paraffin‐embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer‐related genes was sequenced in the RNAlater samples. Results Ninety‐one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51‐70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1‐signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. Conclusions The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted. |
| first_indexed | 2024-12-19T06:23:07Z |
| format | Article |
| id | doaj.art-4914b480ea914398a395b0d48d42e8eb |
| institution | Directory Open Access Journal |
| issn | 2398-8835 |
| language | English |
| last_indexed | 2024-12-19T06:23:07Z |
| publishDate | 2020-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Health Science Reports |
| spelling | doaj.art-4914b480ea914398a395b0d48d42e8eb2022-12-21T20:32:37ZengWileyHealth Science Reports2398-88352020-06-0132n/an/a10.1002/hsr2.155Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017)Christian S. Alvarez0Jeremy Ortiz1Giovanna Bendfeldt‐Avila2Yi Xie3Mingyi Wang4Dongjing Wu5Herbert Higson6Elisa Lee7Kedest Teshome8Joaquin Barnoya9David E. Kleiner10John D. Groopman11Roberto Orozco12Katherine A. McGlynn13Eduardo Gharzouzi14Michael Dean15Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MarylandInstituto de Cancerología/INCAN Guatemala City GuatemalaHospital Centro Médico Militar Guatemala City GuatemalaDivision of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MarylandCancer Genetics Research Laboratory, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc Frederick National Laboratory for Cancer Research Gaithersburg MarylandCancer Genetics Research Laboratory, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc Frederick National Laboratory for Cancer Research Gaithersburg MarylandCancer Genetics Research Laboratory, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc Frederick National Laboratory for Cancer Research Gaithersburg MarylandCancer Genetics Research Laboratory, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc Frederick National Laboratory for Cancer Research Gaithersburg MarylandCancer Genetics Research Laboratory, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc Frederick National Laboratory for Cancer Research Gaithersburg MarylandIntegra Cancer Institute Guatemala City GuatemalaLaboratory of Pathology Center for Cancer Research, NCI, NIH Bethesda MarylandDepartment of Environmental Health and Engineering, Bloomberg School of Public Health Johns Hopkins University Baltimore MarylandDepartment of Pathology Hospital General San Juan de Dios Guatemala City GuatemalaDivision of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MarylandIntegra Cancer Institute Guatemala City GuatemalaDivision of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MarylandAbstract Background and aims Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1‐signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. Methods Formalin‐fixed, paraffin‐embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer‐related genes was sequenced in the RNAlater samples. Results Ninety‐one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51‐70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1‐signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. Conclusions The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted.https://doi.org/10.1002/hsr2.155aflatoxinGuatemalahepatocellular carcinomaR249S mutationTP53 mutation |
| spellingShingle | Christian S. Alvarez Jeremy Ortiz Giovanna Bendfeldt‐Avila Yi Xie Mingyi Wang Dongjing Wu Herbert Higson Elisa Lee Kedest Teshome Joaquin Barnoya David E. Kleiner John D. Groopman Roberto Orozco Katherine A. McGlynn Eduardo Gharzouzi Michael Dean Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017) Health Science Reports aflatoxin Guatemala hepatocellular carcinoma R249S mutation TP53 mutation |
| title | Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017) |
| title_full | Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017) |
| title_fullStr | Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017) |
| title_full_unstemmed | Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017) |
| title_short | Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross‐sectional study (2016‐2017) |
| title_sort | analysis of tp53 aflatoxin signature mutation in hepatocellular carcinomas from guatemala a cross sectional study 2016 2017 |
| topic | aflatoxin Guatemala hepatocellular carcinoma R249S mutation TP53 mutation |
| url | https://doi.org/10.1002/hsr2.155 |
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