Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Bamba‐Funck, Jessica; Layese, Richard; Trépo, Eric; Zucman–Rossi, Jessica; Cagnot, Carole; Guyot, Erwan; Ziol, Marianne; Sutton, Angéla; Audureau, Étienne; Nahon, Pierre; Asselah, Tarik; Guyader, Dominique; Fontaine, Hélène; Pageaux, Georges‐Philippe; Ouzan, Denis; Zoulim, Fabien; Bronowicki, Jean–Pierre; Decaensi, Thomas; Riachi, Ghassan; Calès, Paul; Alric, Laurent; Bourlière, Marc; Dharancy, Sébastien; Blanc, Jean‐Frédéric; Abergel, Armand; Chazouillères, Olivier; Mallat, Ariane; Grangé, Jean‐Didier; Attali, P; Wartelle, Claire; Thabut, Dominique; Pilette, Christophe; Silvain, Christine; Christidis, Christos; Bernard‐Chabert, Brigitte; Hillaire, Sophie; Martino, Vincent Di; Ganne‐Carrié, Nathalie; Chaffaut, Cendrine; Archambeaud, Isabelle; d’Altéroche, Louis; Oberti, Frédéric; Roulot, Dominique; Moreno, Christophe; Louvet, Alexandre; Dao, Thông; Moirand, Romain; Goria, Odile; Nguyen‐Khac, Eric; Carbonell, Nicolas; Duclos‐Vallée, Jean‐Charles; Pol, Stanislas; Lédinghen, Victor de; Ozenne, Violaine; Henrion, Jean; Péron, Jean‐Marie; Tran, Albert; Perlemuter, Gabriel; Zarski, Jean–Pierre; Chevret, Sylvie

doi:10.1016/j.jhep.2022.11.003

Cited by 34 publications

(20 citation statements)

References 44 publications

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“…constructed a wGRS model utilizing three genetic variations in a European population and the results showed that the individuals in the high genetic risk category (Scores 5–6) were 29 times more likely to develop HCC. Nahon et al 14 . discovered that a 7‐SNPs wGRS could be an independent risk factor to predict 5‐year HCC incidence.…”

Section: Discussionmentioning

confidence: 99%

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A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population

Zou,

Zhu,

Song

et al. 2024

Cancer Medicine

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AimsThis study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS).MethodsA case–control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta‐analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models.ResultsA total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84–0.89; AUC: 0.85, 95% CI: 0.81–0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60–0.67; AUC: 0.65, 95% CI: 0.60–0.71).ConclusionsA novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at‐risk individuals for precise prevention.

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Section: Discussionmentioning

confidence: 99%

“…For HCC, previous studies have established wGRS or PRS based on genetic variants in Western populations. 13,14 However, there is a lack of a genetic prediction model for HCC patients in Chinese population due to ethnic differences. Furthermore, PRS could be further developed in combination with nongenetic risk factors.…”

Section: Introductionmentioning

confidence: 99%

A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population

Zou,

Zhu,

Song

et al. 2024

Cancer Medicine

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“…However, it’s noteworthy that in 40-60% of HCC cases, there are no mutations in CTNNB1, Axin1, or Axin2 ( 65 ). Based on this, another variation that controls the pathway was found in a recent genome-wide association study (GWAS) that specifically targeted alcohol-related HCC: the WNT3A-WNT9A gene variants are specifically linked to the occurrence of HCC in alcoholic liver disease patients ( 70 , 71 ).…”

Section: The Role Of the Wnt/β-catenin Signaling Pathway In The Tumor...mentioning

confidence: 99%

Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target

Zhao,

Cui,

Wei

et al. 2024

Front. Oncol.

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Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/β-Catenin signaling pathway is a highly conserved pathway involved in several biological processes, including the improper regulation that leads to the tumorigenesis and progression of cancer. New studies have found that abnormal activation of the Wnt/β-Catenin signaling pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. New perspectives and approaches to treating HCC will arise from understanding this pathway. This article offers a thorough analysis of the Wnt/β-Catenin signaling pathway’s function and its therapeutic implications in HCC.

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“…STK1 (Peutz–Jeghers syndrome) predisposes patients to several tumors, including CRC, PC, GC, and small intestinal cancer [ 83 ]. However, only a relatively small percentage of tumors can be attributed to well-established cancer-related genes [ 85 , 86 , 87 , 88 , 89 ], which does not explain the worldwide increase in the incidence of GI cancers.…”

Section: Common Cellular and Molecular Mechanismsmentioning

confidence: 99%

The Rise of Gastrointestinal Cancers as a Global Phenomenon: Unhealthy Behavior or Progress?

Jardim

Souza

2023

IJERPH

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The overall burden of cancer is rapidly increasing worldwide, reflecting not only population growth and aging, but also the prevalence and spread of risk factors. Gastrointestinal (GI) cancers, including stomach, liver, esophageal, pancreatic, and colorectal cancers, represent more than a quarter of all cancers. While smoking and alcohol use are the risk factors most commonly associated with cancer development, a growing consensus also includes dietary habits as relevant risk factors for GI cancers. Current evidence suggests that socioeconomic development results in several lifestyle modifications, including shifts in dietary habits from local traditional diets to less-healthy Western diets. Moreover, recent data indicate that increased production and consumption of processed foods underlies the current pandemics of obesity and related metabolic disorders, which are directly or indirectly associated with the emergence of various chronic noncommunicable conditions and GI cancers. However, environmental changes are not restricted to dietary patterns, and unhealthy behavioral features should be analyzed with a holistic view of lifestyle. In this review, we discussed the epidemiological aspects, gut dysbiosis, and cellular and molecular characteristics of GI cancers and explored the impact of unhealthy behaviors, diet, and physical activity on developing GI cancers in the context of progressive societal changes.

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Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Cited by 34 publications

References 44 publications

A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population

A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population

Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target

The Rise of Gastrointestinal Cancers as a Global Phenomenon: Unhealthy Behavior or Progress?

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