TY - JOUR
T1 - TP53 R249S mutation, genetic variations in HBX and risk of hepatocellular carcinoma in The Gambia
AU - Gouas, Doriane A.
AU - Villar, Stéphanie
AU - Ortiz-Cuaran, Sandra
AU - Legros, Pénélope
AU - Ferro, Gilles
AU - Kirk, Gregory D.
AU - Lesi, Olufunmilayo A.
AU - Mendy, Maimuna
AU - Bah, Ebrima
AU - Friesen, Marlin D.
AU - Groopman, John
AU - Chemin, Isabelle
AU - Hainaut, Pierre
N1 - Funding Information:
This research was supported in part by National Institutes of Health (NIH) grant (P01 ES006052), in part by the National Cancer Institute, NIH, Department of Health and Human Services grant (N02 CP40521), in part by Association pour la Recherche sur le Cancer (ARC-5044) and in part by the American Cancer Society (MRSG-07-284-01-CCE to G.D.K.).
PY - 2012/11
Y1 - 2012/11
N2 - In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B 1 (AFB 1) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population. HBX (complete or 3'-truncated) and HBS genes were assessed by PCR in cell-free DNA (CFDNA) from plasma of subjects recruited in a hospital-based case-control study (325 controls, 78 cirrhotic patients and 198 HCC cases) conducted in The Gambia. These samples had been previously analyzed for R249S and HBV serological status. Complete HBX sequence was frequently detected in CFDNA of HCC-R249S positive (77%, 43/56) compared with HCC-R249S-negative cases (44%, 22/50). Conversely, the proportion of 3'-truncated HBX gene was significantly higher in HCC-R249S negative than positive cases (34%, 17/50, compared with 12%, 7/56) (χ 2= 12.12; P= 0.002; distribution of R249S negative and positive according to HBX status). Occult HBV infection (detected by PCR) was present in 24% of HCC previously considered as negative by HBV serology. Moreover, HBV mutation analysis revealed that double mutation at nucleotides 1762 T/1764 A was associated with diagnosis of cirrhosis or HCC {cirrhosis: odds ratio (OR): 9.50 [95% confidence interval (CI) 1.50-60.11]; HCC: OR: 11.29 [95% CI 2.07-61.47]}. These findings suggest that in HCC from The Gambia, complete HBX sequences are often associated with the presence of TP53 R249S mutation.
AB - In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B 1 (AFB 1) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population. HBX (complete or 3'-truncated) and HBS genes were assessed by PCR in cell-free DNA (CFDNA) from plasma of subjects recruited in a hospital-based case-control study (325 controls, 78 cirrhotic patients and 198 HCC cases) conducted in The Gambia. These samples had been previously analyzed for R249S and HBV serological status. Complete HBX sequence was frequently detected in CFDNA of HCC-R249S positive (77%, 43/56) compared with HCC-R249S-negative cases (44%, 22/50). Conversely, the proportion of 3'-truncated HBX gene was significantly higher in HCC-R249S negative than positive cases (34%, 17/50, compared with 12%, 7/56) (χ 2= 12.12; P= 0.002; distribution of R249S negative and positive according to HBX status). Occult HBV infection (detected by PCR) was present in 24% of HCC previously considered as negative by HBV serology. Moreover, HBV mutation analysis revealed that double mutation at nucleotides 1762 T/1764 A was associated with diagnosis of cirrhosis or HCC {cirrhosis: odds ratio (OR): 9.50 [95% confidence interval (CI) 1.50-60.11]; HCC: OR: 11.29 [95% CI 2.07-61.47]}. These findings suggest that in HCC from The Gambia, complete HBX sequences are often associated with the presence of TP53 R249S mutation.
UR - http://www.scopus.com/inward/record.url?scp=84864323291&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864323291&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgs135
DO - 10.1093/carcin/bgs135
M3 - Article
C2 - 22759751
AN - SCOPUS:84864323291
SN - 0143-3334
VL - 33
SP - 1219
EP - 1224
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -