A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease

Nischalke, HD; Lutz, P; Krämer, Benjamin; Müller, Tobias; Rosendahl, Jonas; Fischer, John H.; Berg, Thomas; Soyka, Michael; Semmo, Nasser; Nattermann, Jacob; Sauerbruch, Tilman; Strassburg, CP; Stickel, Felix; Spengler, Ulrich

doi:10.1055/s-0034-1386122

Cited by 12 publications

(13 citation statements)

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“…Nischalke et al in a relatively small, multicentre study found a significant risk association between carriage of rs2228603 in neurocan (NCAN) and the development of HCC in patients with alcohol-related cirrhosis [13]. This genetic variant had been linked the development of hepatic steatosis in a previous GWAS in nonalcoholic fatty liver disease (NAFLD) [18].…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis

Stickel

Buch

Nischalke

et al. 2018

American Journal of Gastroenterology

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Section: Discussionmentioning

confidence: 99%

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis

Stickel

Buch

Nischalke

et al. 2018

American Journal of Gastroenterology

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“…A variant in NCAN, an extracellular matrix proteoglycan that was initially identified as a modifier of steatosis during genome-wide association studies performed in patients with non-alcoholic steatohepatitis, 82 was subsequently also associated with the presence of HCC in European patients with ALD. 83 Interestingly, the authors reported a higher rate of HCC among carriers of both the at-risk NCAN-T and PNPLA3-G variants than in those with only one or neither of these genetic traits. Detailed mapping of this region subsequently identified TM6SF2 rs58542926 as the causal variant responsible for all the associations previously reported on the NCAN locus.…”

Section: Key Pointsmentioning

confidence: 97%

Hepatocellular carcinoma in the setting of alcohol-related liver disease

Ganne-Carrié

Nahon

2019

Journal of Hepatology

276

191

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Alcohol-related liver disease is the most prevalent type of chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. Alcohol has been associated with an increased risk of several malignancies, this risk starting at doses as low as 10 g/1 unit/day. The carcinogenic process includes direct acetaldehyde toxicity through the formation of protein and DNA adducts, an increased production of reactive oxygen species, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. A high annual incidence of HCC has been observed in large European cohorts of patients with alcoholic cirrhosis, reaching 2.9%, with numerous host factors modulating this risk (age, gender, liver failure, genetic polymorphisms affecting oncogenic pathways). Because of impaired surveillance and poor patient compliance, HCC is often detected late in patients with chronic liver disease of alcoholic aetiology. This delay in detection, which is frequently made in the context of advanced liver cirrhosis rather than in surveillance programmes, results in more advanced HCC that is less amenable to curative treatment. Consequently, patients with alcohol-related HCC generally have a worse prognosis than those with non-alcoholic HCC.

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“…In patients with established alcohol-related cirrhosis, carriage of rs738409 in PNPLA3 is associated with an increased risk of developing HCC [142,146,[149][150][151][152][153][154][155] (Table 7). A meta-analysis of five of these studies based on individual patient data, confirmed this association (OR = 2.2; 95% CI: 1.8-2.67; p = 4.71 Â 10 À15 ), and showed that it was robust when adjusted for age, sex, and body mass index (OR = 2.13; 95% CI: 1.73-2.61; p = 5.52 Â 10 À13 ) [155].…”

Section: Heritability and Genetic Risk Factorsmentioning

confidence: 99%

The genetics of alcohol dependence and alcohol-related liver disease

Stickel

Moreno

Hampe

et al. 2017

Journal of Hepatology

145

106

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The susceptibility to developing alcohol dependence and significant alcohol-related liver injury is determined by a number of constitutional, environmental and genetic factors, although the nature and level of interplay between them remains unclear. The familiality and heritability of alcohol dependence is well-documented but, to date, no strong candidate genes conferring increased risk have emerged, although variants in alcohol dehydrogenase and acetaldehyde dehydrogenase have been shown to confer protection, predominantly in individuals of East Asian ancestry. Population contamination with confounders such as drug co-dependence and psychiatric and physical co-morbidity may explain the essentially negative genome-wide association studies in this disorder. The familiality and hereditability of alcohol-related cirrhosis is not as well-documented but three strong candidate genes PNPLA3, TM6SF2 and MBOAT7, have been identified. The mechanisms by which variants in these genes confer risk and the nature of the functional interplay between them remains to be determined but, when elucidated, will undoubtedly increase our understanding of the pathophysiology of this disease. The way in which this genetic information could potentially inform patient management has yet to be determined and tested.

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A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease

Cited by 12 publications

References 0 publications

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis

Hepatocellular carcinoma in the setting of alcohol-related liver disease

The genetics of alcohol dependence and alcohol-related liver disease

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