C P Wild

International Agency for Research on Cancer, Lyons, Rhône-Alpes, France

Are you C P Wild?

Claim your profile

Publications (258)1528.69 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants. We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ± 0.9). Aflatoxin exposure in women was assessed using an ELISA method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16 weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was measured using the Illumina Infinium HumanMethylation450beadchip. AF-alb levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure in the mothers was associated to DNA methylation in their infants for 71 CpG sites (false discovery rate < 0.05), with an average effect size of 1.7% change in methylation. Aflatoxin-associated differential methylation was observed in growth factor genes such as FGF12 and IGF1, and immune-related genes such as CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region (corresponding to the miR-4520b locus) was identified. This study shows that maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants, including in genes related to growth and immune function. This reinforces the need for interventions to reduce aflatoxin exposure, especially during critical periods of fetal and infant development. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    International Journal of Epidemiology 04/2015; DOI:10.1093/ije/dyv027 · 9.20 Impact Factor
  • Science 02/2015; 347(6223). DOI:10.1126/science.aaa6799 · 31.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer research is drawing on the human genome project to develop new molecular-targeted treatments. This is an exciting but insufficient response to the growing, global burden of cancer, particularly as the projected increase in new cases in the coming decades is increasingly falling on developing countries. The world is not able to treat its way out of the cancer problem. However, the mechanistic insights from basic science can be harnessed to better understand cancer causes and prevention, thus underpinning a complementary public health approach to cancer control. This manuscript focuses on how new knowledge about the molecular and cellular basis of cancer, and the associated high-throughput laboratory technologies for studying those pathways, can be applied to population-based epidemiological studies, particularly in the context of large prospective cohorts with associated biobanks to provide an evidence base for cancer prevention. This integrated approach should allow a more rapid and informed translation of the research into educational and policy interventions aimed at risk reduction across a population. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    JNCI Journal of the National Cancer Institute 01/2015; 107(1). DOI:10.1093/jnci/dju353 · 15.16 Impact Factor
  • The Lancet 10/2014; 384(9953):1502-3. DOI:10.1016/S0140-6736(14)61918-8 · 45.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aflatoxin and fumonisin are toxic food contaminants. Knowledge about effects of their exposure and co-exposure on child growth is inadequate.
    Environmental Health Perspectives 10/2014; DOI:10.1289/ehp.1408097 · 7.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The association between aflatoxin intake from maize-based weaning food and aflatoxin albumin adducts (AF-alb) was investigated in 148 Tanzanian children aged between 12 and 22 months, at 2 visits 6 months apart. At the first visit (storage season) there was a significant correlation at the individual level between AF-alb (geometric mean 43.2 pg/mg albumin) and aflatoxin intake (geometric mean 81.7 ng/kg b.w./d) through maize-based weaning food (r = 0.51, p < 0.01). Overall, this correlation was r = 0.43 (p < 0.01). The AF-alb level in weaning-age children in Tanzania closely reflects aflatoxin intake from maize in weaning food. Exposure levels suggest children may be at risk from aflatoxin associated health effects.
    Biomarkers 06/2014; DOI:10.3109/1354750X.2014.924998 · 2.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The fungal metabolite aflatoxin is a common contaminant of foodstuffs, especially when stored in damp conditions. In humans, high levels can result in acute hepatic necrosis and death, while chronic exposure is carcinogenic. We conducted a pilot study nested within an existing population cohort (the General Population Cohort), to assess exposure to aflatoxin, among people living in rural south-western Uganda. Sera from 100 adults and 96 children under 3 years of age (85 male, 111 female) were tested for aflatoxin-albumin adduct (AF-alb), using an ELISA assay. Socio-demographic and dietary data were obtained for all participants; HIV serostatus was available for 90 adults and liver function tests (LFTs) for 99. Every adult and all but four children had detectable AF-alb adduct, including five babies reported to be exclusively breastfed. Levels ranged from 0 to 237.7 pg/mg albumin and did not differ significantly between men and women, by age or by HIV serostatus; 25% had levels above 15.1 pg/mg albumin. There was evidence of heterogeneity between villages (P = 0.003); those closest to trading centres had higher levels. Adults who consumed more Matooke (bananas) had lower levels of AF-alb adduct (P = 0.02) than adults who did not, possibly because their diet contained fewer aflatoxin-contaminated foods such as posho (made from maize). Children who consumed soya, which is not grown locally, had levels of AF-alb adduct that were almost twice as high as those who did not eat soya (P = 0.04). Exposure to aflatoxin is ubiquitous among the rural Ugandans studied, with a significant number of people having relatively high levels. Sources of exposure need to be better understood to instigate practical and sustainable interventions.
    Tropical Medicine & International Health 02/2014; DOI:10.1111/tmi.12283 · 2.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To collect information on biobanking facilities in low- and middle-income countries (LMICs) as a first step towards establishing an LMIC biobank and cohort building network (BCNet) to support research, with a focus on cancer control. Method: Sixty centres were identified from sources including cancer centres, universities, hospitals, and public health facilities and invited to participate in a survey between December 2012 and March 2013. Results: Of the 27 centres (45%) that responded, most have existed for <10 years. They store between 1,000 and 1,000,000 research samples as well as samples remaining after clinical diagnosis. Sample storage is mostly in freezers, although 45% (9/20) of the centres do not have regular access to electricity. Biobank managers, sample management systems, and mechanisms for follow-up using linkages are uncommon. Many (80%; 21/26) of the centres have regulations to govern research, but regulations for the use of biobank resources (samples and data) are not well developed. Conclusions: Biobanking facilities are being developed in LMICs. Shortcomings in in ternational visibility, sample sharing regulations, standardization, quality assurance, and sample management systems could be alleviated by international networking. Stakeholders need to work together to increase access to high-quality biological resources for scientific research.
    Pathobiology 01/2014; 81(5-6):252-260. DOI:10.1159/000362093 · 2.32 Impact Factor
  • Christopher P Wild
  • [Show abstract] [Hide abstract]
    ABSTRACT: ScopeThis study explores the relationship between aflatoxin and the insulin-like growth factor (IGF) axis and its potential effect on child growth.Methods and resultsOne hundred and ninety-nine Kenyan schoolchildren were studied for aflatoxin-albumin adduct (AF-alb), IGF1 and IGF-binding protein-3 (IGFBP3) levels using ELISA. AF-alb was inversely associated with IGF1 and IGFBP3 (p < 0.05). Both IGF1 and IGFBP3 were significantly associated with child height and weight (p < 0.01). Children in the highest tertile of AF-alb exposure (>198.5 pg/mg) were shorter than children in the lowest tertile (<74.5 pg/mg), after adjusting for confounders (p = 0.043). Path analysis suggested that IGF1 levels explained ∼16% of the impact of aflatoxin exposure on child height (p = 0.052). To further investigate this putative mechanistic pathway, HHL-16 liver cells (where HHL-16 is human hepatocyte line 16 cells) were treated with aflatoxin B1 (0.5, 5 and 20 μg/mL for 24-48 h). IGF1 and IGFBP3 gene expression measured by quantitative PCR and protein in culture media showed a significant down-regulation of IGF genes and reduced IGF protein levels.Conclusion Aflatoxin treatment resulted in a significant decrease in IGF gene and protein expression in vitro. IGF protein levels were also lower in children with the highest levels of AFB-alb adducts. The data suggest that aflatoxin-induced changes in IGF protein levels could contribute to growth impairment where aflatoxin exposure is high.
    Molecular Nutrition & Food Research 01/2014; 59(3). DOI:10.1002/mnfr.201300619 · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aflatoxin is known to cross the placental barrier and exposures in utero could influence genomic programming, foetal growth and development, resulting in long-term health effects. We aimed to determine aflatoxin exposure in Gambian women at two stages of pregnancy and during the rainy and dry seasons. We examined aflatoxin exposure in pregnant Gambian women at early (<16 weeks) and later (16 weeks onward) stages of pregnancy and at different times of the year, during the rainy (June to October 2009) or dry (November to May 2010) season, using aflatoxin-albumin adducts (AF-alb). Mean AF-alb was higher during the dry season than in the rainy season, in both early and later pregnancy although the difference was strongest in later pregnancy. There was a modest increase in AF-alb in later than early pregnancy (geometric mean 41.8 vs. 34.5 pg/mg, P < 0.05), but this was restricted to the dry season when exposures were generally higher. The study confirmed that Gambian pregnant women were exposed to aflatoxin throughout the pregnancy, with higher levels in the dry season. There was some evidence in the dry season that women in later pregnancy had higher AF-alb levels than those in earlier pregnancy. Further research on the effects of exposure to this potent mutagen and carcinogen throughout pregnancy, including the epigenetic modification of foetal gene expression and impact on pre- and post-natal growth and development, are merited.
    Tropical Medicine & International Health 12/2013; 19(3). DOI:10.1111/tmi.12250 · 2.30 Impact Factor
  • Paolo Vineis, Christopher P Wild
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer is a global and growing, but not uniform, problem. An increasing proportion of the burden is falling on low-income and middle-income countries because of not only demographic change but also a transition in risk factors, whereby the consequences of the globalisation of economies and behaviours are adding to an existing burden of cancers of infectious origin. We argue that primary prevention is a particularly effective way to fight cancer, with between a third and a half of cancers being preventable on the basis of present knowledge of risk factors. Primary prevention has several advantages: the effectiveness could have benefits for people other than those directly targeted, avoidance of exposure to carcinogenic agents is likely to prevent other non-communicable diseases, and the cause could be removed or reduced in the long term-eg, through regulatory measures against occupational or environmental exposures (ie, the preventive effort does not need to be renewed with every generation, which is especially important when resources are in short supply). Primary prevention must therefore be prioritised as an integral part of global cancer control.
    The Lancet 12/2013; 383(9916). DOI:10.1016/S0140-6736(13)62224-2 · 45.22 Impact Factor
  • Source
    Christopher P Wild, Augustin Scalbert, Zdenko Herceg
    [Show abstract] [Hide abstract]
    ABSTRACT: Advances in laboratory sciences offer much in the challenge to unravel the complex etiology of cancer and to therefore provide an evidence-base for prevention. One area where improved measurements are particularly important to epidemiology is exposure assessment; this requirement has been highlighted through the concept of the exposome. In addition, the ability to observe genetic and epigenetic alterations in individuals exposed to putative risk factors also affords an opportunity to elucidate underlying mechanisms of carcinogenesis, which in turn may allow earlier detection and more refined molecular classification of disease. In this context the application of omics technologies to large population-based studies and their associated biobanks raise exciting new avenues of research. This review considers the areas of genomics, transcriptomics, epigenomics and metabolomics and the evidence to date that people exposed to well-defined factors (for example, tobacco, diet, occupational exposures, environmental pollutants) have specific omics profiles. Although in their early stages of development these approaches show promising evidence of distinct exposure-derived biological effects and indicate molecular pathways that may be particularly relevant to the carcinogenic process subsequent to environmental and lifestyle exposures. Such an interdisciplinary approach is vital if the full benefits of advances in laboratory sciences and investments in large-scale prospective cohort studies are to be realized in relation to cancer prevention. Environ. Mol. Mutagen., 2013. © 2013 Wiley Periodicals, Inc.
    Environmental and Molecular Mutagenesis 08/2013; 54(7). DOI:10.1002/em.21777 · 2.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and biomedical research. The result is a broader appreciation of epigenetic phenomena in the etiology of common human diseases, notably cancer. These advances represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, should generate information establishing the "normal" epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Despite epigenetic events emerging as key mechanisms in cancer development, our search of the Monograph Volume 100 revealed that the use of epigenetic data in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs has been modest so far. Here, we review (i) the current status of epigenetics incorporation in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences, (v) critical technological and biological issues in assessing epigenetic carcinogens. We also discuss issues related to opportunities and challenges in applying epigenetic testing in carcinogen identification and evaluation. Although epigenetic assays are just beginning to be applied in carcinogen evaluation, important data are being generated and valuable scientific resources are being established that should catalyze future applications of epigenetic testing.
    Carcinogenesis 06/2013; DOI:10.1093/carcin/bgt212 · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ScopeThe study aims to evaluate the status of dietary exposure to aflatoxin and fumonisin in young Tanzanian children, using previously validated biomarkers of exposure. Methods and resultsA total of 148 children aged 12-22 months, were recruited from three geographically distant villages in Tanzania; Nyabula, Kigwa, and Kikelelwa. Plasma aflatoxin-albumin adducts (AF-alb) and urinary fumonisin B1 (UFB1) were measured by ELISA and LC-MS, respectively. AF-alb was detectable in 84% of children, was highest in fully weaned children (p < 0.01) with higher levels being associated with higher maize intake (p < 0.05). AF-alb geometric mean (95% CI) was 43.2 (28.7-65.0), 19.9 (13.5-29.2), and 3.6 (2.8-4.7) pg/mg albumin in children from Kigwa, Nyabula, and Kikelelwa, respectively. UFB1 was detectable in 96% of children and the level was highest in children who had been fully weaned (p < 0.01). The geometric UFB1 mean (95% CI) was 327.2 (217.1-493.0), 211.7 (161.1-278.1), and 82.8 (58.3-117.7) pg/mL in Kigwa, Nyabula, and Kikelelwa, respectively. About 82% of all the children were exposed to both mycotoxins. Conclusion Young children in Tanzania are chronically exposed to both aflatoxin and fumonisin through contaminated diet, although the level of exposure varies markedly between the three villages studied.
    Molecular Nutrition & Food Research 06/2013; 57(10). DOI:10.1002/mnfr.201300116 · 4.91 Impact Factor
  • Yusuke Shimakawa, Ebrima Bah, Christopher P Wild, Andrew J Hall
    [Show abstract] [Hide abstract]
    ABSTRACT: The Gambia National Cancer Registry (GNCR) is one of the few nationwide population-based cancer registries in sub-Saharan Africa. Most registries in sub-Saharan Africa are limited to cities; therefore, the GNCR is important in providing estimates of cancer incidence in rural Africa. Our study assesses the quality of its data. The methods proposed by Bray and Parkin, and Parkin and Bray (Eur J Cancer 2009;45:747-64) were applied to the registry data from 1990 to 2009 to assess comparability, validity and completeness. The system used for classification and coding of neoplasms followed international standards. The percentage of cases morphologically verified was 18.1% for men and 33.1% for women, and that of death certificate only cases was 6.6 and 3.6%, respectively. Incidence rates in rural regions were lower than in the urban part of the country, except amongst young male adults. Comparison with other West African registries showed that the incidences of liver and uterine cervical cancer were comparable, but those of prostate and breast in The Gambia were relatively low. The overall completeness was estimated at 50.3% using the capture-recapture method. The GNCR applies international standard practices to data collection and handling, providing valuable data on cancer incidence in sub-Saharan Africa. However, the data are incomplete in the rural and elderly populations probably because of health care access and use.
    International Journal of Cancer 02/2013; 132(3). DOI:10.1002/ijc.27646 · 5.01 Impact Factor
  • Silvia Franceschi, Christopher P Wild
    [Show abstract] [Hide abstract]
    ABSTRACT: The number of new cancer cases each year is projected to rise worldwide by about 70% by 2030 due to demographic changes alone, with the largest increases in the lower-income countries. Wider adoption of specific aspects of westernized lifestyles would translate to still greater increases in certain cancer types. In many countries the burden of cancer and other non-communicable diseases will add to communicable diseases and malnutrition to impose a "double burden" on the poorest. These trends represent major challenges to health, poverty, sustainable development and equality. Prevention is, however, possible based on implementing existing knowledge about risk factors and the natural history of the disease. Both primary and secondary cancer prevention offer therefore many opportunities to combat the projected increases. Tobacco control, reductions in obesity and physical inactivity, reduced consumption of alcohol, vaccination against hepatitis B and human papilloma viruses, safe sex, avoidance of environmental and occupational carcinogens and excessive sun exposure as well as the early detection and screening for breast, cervix and colorectal cancers would all make significant contributions. At the same time, for a number of major cancers (e.g., colon, prostate, kidney, pancreas, brain, lympho-haematological malignancies) research is needed to identify as yet unknown risk factors whilst for existing prevention strategies additional work is needed on their implementation into health services. Finally, there is a remarkable opportunity for advances in understanding the molecular basis of carcinogenesis to provide new tools and insights into aetiology and prevention. It is only by complementing efforts to improve treatment with those aimed at prevention that the impending epidemic of this disease can be addressed.
    Molecular oncology 11/2012; 7(1). DOI:10.1016/j.molonc.2012.10.010 · 5.94 Impact Factor
  • Journal of the Royal Society of Medicine 09/2012; 105(9):365-6. DOI:10.1258/jrsm.2012.120207 · 2.02 Impact Factor
  • Nature reviews. Cancer 06/2012; 12(8):503-504. DOI:10.1038/nrc3311 · 37.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester (p = 0.91) or the second trimester (p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy.
    Maternal and Child Health Journal 05/2012; 17(4). DOI:10.1007/s10995-012-1034-7 · 2.24 Impact Factor

Publication Stats

9k Citations
1,528.69 Total Impact Points

Institutions

  • 1987–2014
    • International Agency for Research on Cancer
      • Section of IARC Monographs
      Lyons, Rhône-Alpes, France
  • 1997–2011
    • University of Leeds
      • • Division of Epidemiology
      • • Leeds Institute of Genetics, Health and Therapeutics (LIGHT)
      • • School of Medicine
      Leeds, ENG, United Kingdom
    • Leidos Biomedical Research
      Maryland, United States
  • 2006
    • Johns Hopkins University
      • Department of Environmental Health Sciences
      Baltimore, MD, United States
  • 1986–2005
    • The University of York
      • Epidemiology and Genetics Unit
      York, ENG, United Kingdom
  • 2004
    • Johannes Gutenberg-Universität Mainz
      • Department of Pharmacology
      Mainz, Rhineland-Palatinate, Germany
    • National Institutes of Health
      Maryland, United States
  • 1993
    • University of Dundee
      Dundee, Scotland, United Kingdom
    • Fujita Health University
      • Department of Pathology
      Nagoya, Aichi, Japan
  • 1992
    • National Cancer Institute Thailand
      Krung Thep, Bangkok, Thailand
  • 1991
    • University of Wuerzburg
      • Institute for Pharmacology and Toxicology
      Würzburg, Bavaria, Germany
  • 1990
    • Unité Inserm U1077
      Caen, Lower Normandy, France