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- Title
Seasonal Variation in TP53 R249S-Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus Infection.
- Authors
Villar, Stephanie; Roux-Goglin, Emilie Le; Gouas, Doriane A.; Plymoth, Amelie; Ferro, Gilles; Boniol, Mathieu; Lereau, Myriam; Bah, Ebrima; Hall, Andrew J.; Wild, Christopher P.; Mendy, Maimuna; Norder, Helene; Sande, Marianne van der; Whittle, Hilton; Friesen, Marlin D.; Groopman, John D.; Hainaut, Pierre
- Abstract
Background: Chronic hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) exposure are etiological factors for hepatocellular carcinoma (HCC) in countries with hot, humid climates. HCC often harbors a TP53 (tumor protein p53) mutation at codon 249 (R249S). In chronic carriers, 1762T/1764A mutations in the HBV X gene are associated with increased HCC risk. Both mutations have been detected in circulating cell-free DNA (CFDNA) from asymptomatic HBV carriers. Objective: We evaluated seasonal variation in R249S and HBV in relation to AFB1 exposure. Methods: R249S was quantitated by mass spectrometry in CFDNA in a cross-sectional survey of 473 asymptomatic subjects (237 HBV carriers and 236 noncarriers) recruited in three villages in the Gambia over a 10?month period. 1762T/1764A HBV mutations were detected by quantitative polymerase chain reaction. In addition, the HBV S gene was sequenced in 99 subjects positive for HBV surface antigen (HBsAg). Results: We observed a seasonal variation of serum R249S levels. Positivity for R249S and average concentration were significantly higher in HBsAg-positive subjects surveyed during April-July (61%; 5,690 ± 11,300 R249S copies/mL serum) than in those surveyed October-March [32% and 480 ± 1,030 copies/mL serum (odds ratio = 3.59; 95% confidence interval: 2.05, 6.30; p < 0.001)]. Positivity for HBV e antigen (HBeAg) (a marker of HBV replication) and viral DNA load also varied seasonally, with 15-30% of subjects surveyed between April and June HBeAg positive, compared with < 10% surveyed during other months. We detected 1762T/1764A mutations in 8% of carriers, half of whom were positive for R249S. We found HBV genotype E in 95 of 99 HBsAgpositive subjects. Conclusion: R249S is detectable in CFDNA of asymptomatic subjects. Evidence of temporal and quantitative variations suggests an interaction among AFB1 exposure, HBV positivity, and replication on TP53 mutation formation or persistence.
- Subjects
GAMBIA; AFLATOXINS; ANALYSIS of variance; CHRONIC diseases; CONFIDENCE intervals; DIET; EPIDEMIOLOGY; HEPATITIS B; HEPATOCELLULAR carcinoma; IMMUNOENZYME technique; MASS spectrometry; GENETIC mutation; POLYMERASE chain reaction; RADIOIMMUNOASSAY; RESEARCH funding; RURAL conditions; SEASONS; T-test (Statistics); LOGISTIC regression analysis; DATA analysis; DATA analysis software; OLIGONUCLEOTIDE arrays
- Publication
Environmental Health Perspectives, 2011, Vol 119, Issue 11, p1635
- ISSN
0091-6765
- Publication type
Article
- DOI
10.1289/ehp.1103539