The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization
ABSTRACT Background and Aims Nonalcoholic fatty liver disease (NAFLD) is an escalating global health concern with significant implications for cancers. A better understanding of the causal relationship between NAFLD and extrahepatic cancers might help in clinical management of NAFLD and prevent its...
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Wiley
2025-03-01
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| Series: | Health Science Reports |
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| Online Access: | https://doi.org/10.1002/hsr2.70551 |
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| author | Wei Wang Pengfei Sun Xintian Ren Tingting Lv Min Li |
| author_facet | Wei Wang Pengfei Sun Xintian Ren Tingting Lv Min Li |
| author_sort | Wei Wang |
| collection | DOAJ |
| description | ABSTRACT Background and Aims Nonalcoholic fatty liver disease (NAFLD) is an escalating global health concern with significant implications for cancers. A better understanding of the causal relationship between NAFLD and extrahepatic cancers might help in clinical management of NAFLD and prevent its adverse outcomes. Methods This study encompassed two complementary approaches. First, the cross‐sectional analysis was performed to examine the association between NAFLD and extrahepatic cancers, utilizing individual‐level data from the National Health and Nutrition Examination Survey (2017‐March 2020, 2021‐2023 cycles). Logistic regression model was utilized to evaluate the association. Subsequently, Mendelian randomization (MR) analysis was conducted to explore the causal association between NAFLD and extrahepatic cancers. Summary‐level data for genetically predicted NAFLD and extrahepatic cancers were derived from large‐scale genome‐wide association studies (GWAS), IEU Open GWAS project and the UK Biobank. The inverse variance weighting (IVW) method with a random‐effect model was utilized as the main analysis. Results A total of 10,010 participants were included in the cross‐sectional analysis. No association was observed between NAFLD and extrahepatic cancers after adjusting for potential confounders, with odd ratios (ORs) ranging from 0.872 to 2.171. IVW MR analysis showed genetic liability to genetically predicted cALT and imaging‐and‐biopsy confirmed NAFLD were not causally associated with extrahepatic cancers, with ORs ranging from 0.957 to 1.118 (all p > 0.050). Moreover, genetically predicted cALT and imaging‐and‐biopsy confirmed NAFLD were causally associated with liver & bile duct cancer (OR = 1.001, 95% CI = 1.000–1.001, p = 0.011; OR = 1.001, 95% CI = 1.000–1.001, p < 0.001), reinforcing a well‐documented link between NAFLD and liver & bile duct cancer. Conclusion Our findings demonstrated that NAFLD was not causally associated with common extrahepatic cancers. Further research is required to validate these results from a mechanistic perspective. |
| format | Article |
| id | doaj-art-969a44d8a0ec4e6393e864cbb0d9c0cd |
| institution | Kabale University |
| issn | 2398-8835 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Health Science Reports |
| spelling | doaj-art-969a44d8a0ec4e6393e864cbb0d9c0cd2025-08-20T03:42:22ZengWileyHealth Science Reports2398-88352025-03-0183n/an/a10.1002/hsr2.70551The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian RandomizationWei Wang0Pengfei Sun1Xintian Ren2Tingting Lv3Min Li4Department of Clinical Laboratory, Beijing Friendship Hospital Capital Medical University Beijing ChinaDepartment of Ultrasound, Beijing Friendship Hospital Capital Medical University Beijing ChinaClinical Epidemiology and EBM Unit, Beijing Friendship Hospital Capital Medical University Beijing ChinaLiver Center, Beijing Friendship Hospital Capital Medical University Beijing ChinaClinical Epidemiology and EBM Unit, Beijing Friendship Hospital Capital Medical University Beijing ChinaABSTRACT Background and Aims Nonalcoholic fatty liver disease (NAFLD) is an escalating global health concern with significant implications for cancers. A better understanding of the causal relationship between NAFLD and extrahepatic cancers might help in clinical management of NAFLD and prevent its adverse outcomes. Methods This study encompassed two complementary approaches. First, the cross‐sectional analysis was performed to examine the association between NAFLD and extrahepatic cancers, utilizing individual‐level data from the National Health and Nutrition Examination Survey (2017‐March 2020, 2021‐2023 cycles). Logistic regression model was utilized to evaluate the association. Subsequently, Mendelian randomization (MR) analysis was conducted to explore the causal association between NAFLD and extrahepatic cancers. Summary‐level data for genetically predicted NAFLD and extrahepatic cancers were derived from large‐scale genome‐wide association studies (GWAS), IEU Open GWAS project and the UK Biobank. The inverse variance weighting (IVW) method with a random‐effect model was utilized as the main analysis. Results A total of 10,010 participants were included in the cross‐sectional analysis. No association was observed between NAFLD and extrahepatic cancers after adjusting for potential confounders, with odd ratios (ORs) ranging from 0.872 to 2.171. IVW MR analysis showed genetic liability to genetically predicted cALT and imaging‐and‐biopsy confirmed NAFLD were not causally associated with extrahepatic cancers, with ORs ranging from 0.957 to 1.118 (all p > 0.050). Moreover, genetically predicted cALT and imaging‐and‐biopsy confirmed NAFLD were causally associated with liver & bile duct cancer (OR = 1.001, 95% CI = 1.000–1.001, p = 0.011; OR = 1.001, 95% CI = 1.000–1.001, p < 0.001), reinforcing a well‐documented link between NAFLD and liver & bile duct cancer. Conclusion Our findings demonstrated that NAFLD was not causally associated with common extrahepatic cancers. Further research is required to validate these results from a mechanistic perspective.https://doi.org/10.1002/hsr2.70551cancercausalityepidemiologyMendelian randomizationnonalcoholic fatty liver disease |
| spellingShingle | Wei Wang Pengfei Sun Xintian Ren Tingting Lv Min Li The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization Health Science Reports cancer causality epidemiology Mendelian randomization nonalcoholic fatty liver disease |
| title | The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization |
| title_full | The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization |
| title_fullStr | The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization |
| title_full_unstemmed | The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization |
| title_short | The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population‐Based Cohort and Mendelian Randomization |
| title_sort | effect of nonalcoholic fatty liver disease on extrahepatic cancers evidence from population based cohort and mendelian randomization |
| topic | cancer causality epidemiology Mendelian randomization nonalcoholic fatty liver disease |
| url | https://doi.org/10.1002/hsr2.70551 |
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