{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:26:11Z","timestamp":1791307571689,"version":"4.3.1"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2356,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>Objective: We evaluated seasonal variation in R249S and HBV in relation to AFB1 exposure.<\/jats:p>\n                  <jats:p>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).<\/jats:p>\n                  <jats:p>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\u2013July (61%; 5,690 \u00b1 11,300 R249S copies\/mL serum) than in those surveyed October\u2013March [32% and 480 \u00b1 1,030 copies\/mL serum (odds ratio = 3.59; 95% confidence interval: 2.05, 6.30; p &amp;lt; 0.001)]. Positivity for HBV e antigen (HBeAg) (a marker of HBV replication) and viral DNA load also varied seasonally, with 15\u201330% of subjects surveyed between April and June HBeAg positive, compared with &amp;lt; 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 HBsAg-positive subjects.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1289\/ehp.1103539","type":"journal-article","created":{"date-parts":[[2011,7,18]],"date-time":"2011-07-18T14:48:06Z","timestamp":1311000486000},"page":"1635-1640","source":"Crossref","is-referenced-by-count":37,"title":["Seasonal Variation in\n                    <i>TP53 R249S<\/i>\n                    -Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus Infection"],"prefix":"10.1021","volume":"119","author":[{"given":"St\u00e9phanie","family":"Villar","sequence":"first","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Le Roux-Goglin","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriane A.","family":"Gouas","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Plymoth","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Ferro","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Boniol","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Lereau","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebrima","family":"Bah","sequence":"additional","affiliation":[{"name":"Gambia Hepatitis Intervention Study, Laboratories Fajara, Banjul, the Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Wild","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maimuna","family":"Mendy","sequence":"additional","affiliation":[{"name":"Medical Research Council, Laboratories Fajara, Banjul, the Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Norder","sequence":"additional","affiliation":[{"name":"Swedish Institute for Infectious Disease Control, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"van der Sande","sequence":"additional","affiliation":[{"name":"National Institute for Public Health and the Environment, Bilthoven, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilton","family":"Whittle","sequence":"additional","affiliation":[{"name":"Gambia Hepatitis Intervention Study, Laboratories Fajara, Banjul, the Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlin D.","family":"Friesen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Groopman","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Hainaut","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2011,7,18]]},"reference":[{"key":"2026080610035189400_micit1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1365-2613.2001.iep178.x","article-title":"Hepatitis B virus and hepatocellular 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Profile of Achievements, 1994\u20132001.Available: http:\/\/www.statehouse.gm\/agriculture\/achievements.html [accessed 11 July 2011]."},{"key":"2026080610035189400_micit7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.mrrev.2006.11.002","article-title":"Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance.","volume":"635","author":"Gormally","year":"2007","journal-title":"Mutat Res"},{"key":"2026080610035189400_micit8","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1158\/0008-5472.CAN-05-4556","article-title":"TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study.","volume":"66","author":"Gormally","year":"2006","journal-title":"Cancer Res"},{"key":"2026080610035189400_micit9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.canlet.2009.02.057","article-title":"The aflatoxin-induced TP53 mutation at codon 249 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