Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
Standard
Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study. / Buch, Stephan; Innes, Hamish; Lutz, Philipp Ludwig; Nischalke, Hans Dieter; Marquardt, Jens U; Fischer, Janett; Weiss, Karl Heinz; Rosendahl, Jonas; Marot, Astrid; Krawczyk, Marcin; Casper, Markus; Lammert, Frank; Eyer, Florian; Vogel, Arndt; Marhenke, Silke; von Felden, Johann; Sharma, Rohini; Atkinson, Stephen Rahul; McQuillin, Andrew; Nattermann, Jacob; Schafmayer, Clemens; Franke, Andre; Strassburg, Christian; Rietschel, Marcella; Altmann, Heidi; Sulk, Stefan; Thangapandi, Veera Raghavan; Brosch, Mario; Lackner, Carolin; Stauber, Rudolf E; Canbay, Ali; Link, Alexander; Reiberger, Thomas; Mandorfer, Mattias; Semmler, Georg; Scheiner, Bernhard; Datz, Christian; Romeo, Stefano; Ginanni Corradini, Stefano; Irving, William Lucien; Morling, Joanne R; Guha, Indra Neil; Barnes, Eleanor; Ansari, M Azim; Quistrebert, Jocelyn; Valenti, Luca; Müller, Sascha A; Morgan, Marsha Yvonne; Dufour, Jean-François; Trebicka, Jonel; Berg, Thomas; Deltenre, Pierre; Mueller, Sebastian; Hampe, Jochen; Stickel, Felix.
In: GUT, Vol. 72, No. 2, 02.2023, p. 381-391.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
AU - Buch, Stephan
AU - Innes, Hamish
AU - Lutz, Philipp Ludwig
AU - Nischalke, Hans Dieter
AU - Marquardt, Jens U
AU - Fischer, Janett
AU - Weiss, Karl Heinz
AU - Rosendahl, Jonas
AU - Marot, Astrid
AU - Krawczyk, Marcin
AU - Casper, Markus
AU - Lammert, Frank
AU - Eyer, Florian
AU - Vogel, Arndt
AU - Marhenke, Silke
AU - von Felden, Johann
AU - Sharma, Rohini
AU - Atkinson, Stephen Rahul
AU - McQuillin, Andrew
AU - Nattermann, Jacob
AU - Schafmayer, Clemens
AU - Franke, Andre
AU - Strassburg, Christian
AU - Rietschel, Marcella
AU - Altmann, Heidi
AU - Sulk, Stefan
AU - Thangapandi, Veera Raghavan
AU - Brosch, Mario
AU - Lackner, Carolin
AU - Stauber, Rudolf E
AU - Canbay, Ali
AU - Link, Alexander
AU - Reiberger, Thomas
AU - Mandorfer, Mattias
AU - Semmler, Georg
AU - Scheiner, Bernhard
AU - Datz, Christian
AU - Romeo, Stefano
AU - Ginanni Corradini, Stefano
AU - Irving, William Lucien
AU - Morling, Joanne R
AU - Guha, Indra Neil
AU - Barnes, Eleanor
AU - Ansari, M Azim
AU - Quistrebert, Jocelyn
AU - Valenti, Luca
AU - Müller, Sascha A
AU - Morgan, Marsha Yvonne
AU - Dufour, Jean-François
AU - Trebicka, Jonel
AU - Berg, Thomas
AU - Deltenre, Pierre
AU - Mueller, Sebastian
AU - Hampe, Jochen
AU - Stickel, Felix
N1 - © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/2
Y1 - 2023/2
N2 - OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis.DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina).RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44).CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
AB - OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis.DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina).RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44).CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
U2 - 10.1136/gutjnl-2022-327196
DO - 10.1136/gutjnl-2022-327196
M3 - SCORING: Journal article
C2 - 35788059
VL - 72
SP - 381
EP - 391
JO - GUT
JF - GUT
SN - 0017-5749
IS - 2
ER -