Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma

Abdellah Akil, Sayeh Ezzikouri, Abdellah Essaid El Feydi, Mustapha Benazzouz, Rajaa Afifi, Ama Gassama Diagne, Aziz Benjouad, Anne Dejean, Pascal Pineau, Soumaya Benjelloun

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background and aims: 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. Materials and 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). Conclusion: 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.

Original languageEnglish (US)
JournalCancer Epidemiology
Volume36
Issue number5
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Hepatocellular Carcinoma
Genotype
Chromosomal Instability
Histone Acetyltransferases
Morocco
Mutation
Epigenomics
Codon
Population
Case-Control Studies
Cause of Death
Neoplasms
Carcinogenesis
Control Groups
Genes

Keywords

  • EP300
  • Genetic susceptibility
  • Histone acetyltransferases
  • Liver cancer
  • PCAF

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Epidemiology

Cite this

Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma. / Akil, Abdellah; Ezzikouri, Sayeh; El Feydi, Abdellah Essaid; Benazzouz, Mustapha; Afifi, Rajaa; Diagne, Ama Gassama; Benjouad, Aziz; Dejean, Anne; Pineau, Pascal; Benjelloun, Soumaya.

In: Cancer Epidemiology, Vol. 36, No. 5, 10.2012.

Research output: Contribution to journalArticle

Akil, A, Ezzikouri, S, El Feydi, AE, Benazzouz, M, Afifi, R, Diagne, AG, Benjouad, A, Dejean, A, Pineau, P & Benjelloun, S 2012, 'Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma', Cancer Epidemiology, vol. 36, no. 5. https://doi.org/10.1016/j.canep.2012.05.011
Akil, Abdellah ; Ezzikouri, Sayeh ; El Feydi, Abdellah Essaid ; Benazzouz, Mustapha ; Afifi, Rajaa ; Diagne, Ama Gassama ; Benjouad, Aziz ; Dejean, Anne ; Pineau, Pascal ; Benjelloun, Soumaya. / Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma. In: Cancer Epidemiology. 2012 ; Vol. 36, No. 5.
@article{f65ba7e8786f482a81e2415481edbde4,
title = "Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma",
abstract = "Background and aims: 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. Materials and 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). Conclusion: 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.",
keywords = "EP300, Genetic susceptibility, Histone acetyltransferases, Liver cancer, PCAF",
author = "Abdellah Akil and Sayeh Ezzikouri and {El Feydi}, {Abdellah Essaid} and Mustapha Benazzouz and Rajaa Afifi and Diagne, {Ama Gassama} and Aziz Benjouad and Anne Dejean and Pascal Pineau and Soumaya Benjelloun",
year = "2012",
month = "10",
doi = "10.1016/j.canep.2012.05.011",
language = "English (US)",
volume = "36",
journal = "Cancer Epidemiology",
issn = "1877-7821",
publisher = "Elsevier BV",
number = "5",

}

TY - JOUR

T1 - Associations of genetic variants in the transcriptional coactivators EP300 and PCAF with hepatocellular carcinoma

AU - Akil, Abdellah

AU - Ezzikouri, Sayeh

AU - El Feydi, Abdellah Essaid

AU - Benazzouz, Mustapha

AU - Afifi, Rajaa

AU - Diagne, Ama Gassama

AU - Benjouad, Aziz

AU - Dejean, Anne

AU - Pineau, Pascal

AU - Benjelloun, Soumaya

PY - 2012/10

Y1 - 2012/10

N2 - Background and aims: 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. Materials and 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). Conclusion: 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.

AB - Background and aims: 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. Materials and 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). Conclusion: 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.

KW - EP300

KW - Genetic susceptibility

KW - Histone acetyltransferases

KW - Liver cancer

KW - PCAF

UR - http://www.scopus.com/inward/record.url?scp=84865861864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865861864&partnerID=8YFLogxK

U2 - 10.1016/j.canep.2012.05.011

DO - 10.1016/j.canep.2012.05.011

M3 - Article

C2 - 22709982

AN - SCOPUS:84865861864

VL - 36

JO - Cancer Epidemiology

JF - Cancer Epidemiology

SN - 1877-7821

IS - 5

ER -