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- Buch, S., et al.
(författare)
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Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
- 2023
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 72:2, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- 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=6.41x10(-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=7.94x10(-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=2.12x10(-44)). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
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| 2. |
- Wernly, S, et al.
(författare)
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A sex-specific propensity-adjusted analysis of colonic adenoma detection rates in a screening cohort
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 17785-
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of colorectal adenoma and advanced adenoma (AA) differs between sexes. Also, the optimal age for the first screening colonoscopy is under debate. We, therefore, performed a sex-specific and age-adjusted comparison of adenoma, AA and advanced neoplasia (AN) rates in a real-world screening cohort. In total, 2824 asymptomatic participants between 45- and 60-years undergoing screening colonoscopy at a single-centre in Austria were evaluated. 46% were females and mean age was 53 ± 4 years. A propensity score for being female was calculated, and adenoma, AA and AN detection rates evaluated using uni- and multivariable logistic regression. Sensitivity analyses for three age groups (group 1: 45 to 49 years, n = 521, 41% females, mean age 47 ± 1 years; group 2: 50 to 54 years, n = 1164, 47% females, mean age 52 ± 1 years; group 3: 55 to 60 years, n = 1139, 46% females, mean age 57 ± 2 years) were performed. The prevalence of any adenoma was lower in females (17% vs. 30%; OR 0.46, 95% CI 0.38–0.55; p < 0.001) and remained so after propensity score adjustment for baseline characteristics and lifestyle factors (aOR 0.52, 95% CI 0.41–0.66; p < 0.001). The same trend was seen for AA with a significantly lower prevalence in females (3% vs. 7%; OR 0.38, 95% CI 0.26–0.55; p < 0.001) that persisted after propensity score adjustment (aOR 0.54, 95% CI 0.34–0.86; p = 0.01). Also, all age-group sensitivity analyses showed lower adenoma, AA and AN rates in females. Similar numbers needed to screen to detect an adenoma, an AA or AN were found in female age group 3 and male age group 1. Colorectal adenoma, AA and AN were consistently lower in females even after propensity score adjustment and in all age-adjusted sensitivity analyses. Our study may add to the discussion of the optimal age for initial screening colonoscopy which may differ between the sexes.
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