Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is a common cause of death by cancer worldwide. In Morocco, HCC is characterized by few mutations and a mild chromosome instability suggesting that epigenetic changes may represent the driving force of tumorigenesis in the region. Recently, three studies looked for an association between EP300 or PCAF polymorphisms and cancer but there is a conspicuous lack of data regarding these histone acetyltransferase (HAT) variants and HCC development. The aim of the current study was to assess the impact of the Ile997Val in EP300 and Asn386Ser in PCAF polymorphisms on the risk of HCC.


METHODS
We performed a case-control study comparing 94 cases with HCC and 220 matching controls. Sequencing methods were used to determine the genotype at the Ile997Val and Asn386Ser on EP300 and PCAF.


RESULTS
We found an overall association between genotypes Val/Val in EP300 and HCC risk (OR, 3.03; 95% CI, 1.08-8.47; P=0.028). Population stratifications revealed a trend or significantly higher risks of HCC development for women and HCV-negative patients carrying the EP300 Val/Val genotype (OR, 4.06; 95% CI, 0.71-23.36; P=0.09 and OR, 4.48; 95% CI, 1.04-19.14; P=0.02, respectively). The PCAF Ser/Ser genotype at codon 386 was more frequent in HCC cases than in control group (P=0.03). We observed trends for higher risk of HCC among men and/or HCV-negative patients carrying Ser/Ser genotype when compared with controls (OR, 10.62; 95% CI, 0.50-225.13 and OR, 11.78; 95% CI, 0.47-295.56, respectively).


CONCLUSIONS
It appears that variants of the transcriptional coactivator genes (EP300 and PCAF) may influence HCC risk in populations with low mutations or chromosomal instability rates. Additional surveys are warranted to confirm this first report.
Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco. abdellah.akil@u-psud.fr
Abdellah
A
Akil
Sayeh
S
Ezzikouri
Abdellah Essaid
AE
El Feydi
Mustapha
M
Benazzouz
Rajaa
R
Afifi
Ama Gassama
AG
Diagne
Aziz
A
Benjouad
Anne
A
Dejean
Pascal
P
Pineau
Soumaya
S
Benjelloun
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D043171:Chromosomal Instability / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D020125:Mutation, Missense; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D050880:p300-CBP Transcription Factors / Q000235:genetics*; D000099224:p300-CBP-Associated Factor
D050881:E1A-Associated p300 Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494360:EP300 protein, human