Abstract:Approximately 8% of the world population and 35 to 45% of East Asians are carriers of the hereditary disorder, aldehyde dehydrogenase 2 (ALDH2) deficiency. ALDH2 plays a central role in the liver to metabolize ethanol. With the common E487K variant, there is a deficiency of ALDH2 function; when ethanol is consumed, there is a systemic accumulation of acetaldehyde, an intermediate product in ethanol metabolism. In ALDH2 deficient individuals, ethanol consumption acutely causes the “Alcohol Flushing Syndrome” wi… Show more
“…An underlying explanation for this disparity among populations is the genetic sensitivity to alcohol's effect on PCa risk [24]. It is reported that the carrier rate of hereditary disorder aldehyde dehydrogenase 2 (ALDH2) deficiency is much higher in East Asians compared to Europeans [25]. A high probability of carrying ALDH2 deficiency combined with frequent alcohol consumption may result in a greater excess risk for PCa in individuals of East Asian ancestry.…”
Objective: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. Methods: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). Results: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09–3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01–1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00–1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88–0.96, p = 0.001) was a protective factor for PCa. Conclusions: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.
“…An underlying explanation for this disparity among populations is the genetic sensitivity to alcohol's effect on PCa risk [24]. It is reported that the carrier rate of hereditary disorder aldehyde dehydrogenase 2 (ALDH2) deficiency is much higher in East Asians compared to Europeans [25]. A high probability of carrying ALDH2 deficiency combined with frequent alcohol consumption may result in a greater excess risk for PCa in individuals of East Asian ancestry.…”
Objective: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. Methods: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). Results: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09–3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01–1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00–1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88–0.96, p = 0.001) was a protective factor for PCa. Conclusions: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.
Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Although alcohol consumption is a well-known risk factor for the development, morbidity, and mortality of HCC globally, alcohol-associated HCC (A-HCC) is poorly characterized compared to viral hepatitis-associated HCC. Most A-HCCs develop post alcohol-associated cirrhosis, but the direct carcinogenesis from ethanol and its metabolites to A-HCC remains obscure. The differences between A-HCC and HCCs caused by other etiologies have not been well investigated in terms of clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, and heterogeneity. Moreover, there is a huge gap between basic research and clinical practice due to the lack of pre-clinical models of A-HCC. In the current review, we discuss the pathogenesis, heterogeneity, preclinical approaches, epigenetic and genetic profiles of A-HCC, and discuss the current insights into and the prospects for future research on A-HCC. The potential effect of alcohol on cholangiocarcinoma and liver metastasis are also discussed.
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