Page 44 - ebook HCC

GENEVA, SWITZERLAND EASL HCC SUMMIT 43
FEBRUARY 13 - 16, 2014
DISCOVER NOW THE

GENETIC PREDISPOSITION TO
HEPATOCELLULAR CARCINOMA

Pierre Nahon 1 2
1 Liver Unit, Jean Verdier Hospital and University Paris 13, Bondy, Inserm U674,
2
Université Paris 5, Paris, France
Corresponding author’s e-mail: pierre.nahon@jvr.aphp.fr

Liver carcinogenesis is a complex and multi-factorial process, in which both environmental
and genetic features interfere and contribute to malignant transformation. Patients with
cirrhosis are particularly exposed and justify periodical screening in order to detect the
early development of hepatocellular carcinoma (HCC). The risk of HCC is, however, not
identical from one patient to another. This observation suggests the implication of host
genetic factors that might not only predispose to a higher risk of HCC emergence in specific
sub-groups, but also to differences in tumour aggressiveness. The identification of these
host factors may improve our understanding of the implications of the various biological
pathways involved in liver carcinogenesis; such progress may as well help to refine the
selection of patients who could benefit from specific preventative measures or could BASIC SPEAKERS ABSTRACTS
be given adapted screening policies. Numerous candidate-gene studies have reported
associations between single nucleotide polymorphisms (SNPs) and the presence of HCC.
Some of these publications unfortunately suffer from major methodological drawbacks
because of their case-control, retrospective and mono-centric aspect. Prospective cohort
studies conducted in large homogeneous populations and comprising a sufficient number
of events during follow-up may overcome these pitfalls, but require a long time to be
conducted and are still scarce. More recently, the first Genome Wide Association studies
(GWAs) have enabled the identification of unsuspected loci that may be involved in various
steps implicated in liver tumourigenesis, but have been so far restricted to Asian patients
chronically infected by HBV or HCV. Taken together, these studies highlight variants that
modulate oxidative stress, iron metabolism, inflammatory and immune responses, DNA-
repair mechanisms or systems involved in cell-cycle regulation as genetic traits susceptible
Available to influence the risk of HCC occurrence. Research in this field will continue to benefit
for all EASL from both progress in genomics technology and coordinated work for the establishment
of large cohorts of well-defined patients. The incorporation of numerous variants in risk-
members assessment models to predict HCC occurrence in prospective cohorts of cirrhotic patients
should enable to highlight gene–gene interactions, assess polygenic predictive scores
and may allow implementation of genetic-based screening or preventative strategies.
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