[Show abstract][Hide abstract] ABSTRACT: Cancer burden worldwide is projected to rise from 14 million new cases in 2012 to 24 million in 2035. While the greatest increases will be in developing countries, where cancer services are already hard pressed, even the richest nations will struggle to meet demands of increasing patient numbers and spiralling treatment costs. No country can treat its way out of the cancer problem. Consequently, cancer control must combine improvements in treatment with greater emphasis on prevention and early detection. Cancer prevention is founded on describing the burden of cancer, identifying the causes and evaluating and implementing preventive interventions. Around 40-50% of cancers could be prevented if current knowledge about risk factors was translated into effective public health strategies. The benefits of prevention are attested to by major successes, for example, in tobacco control, vaccination against oncogenic viruses, reduced exposure to environmental and occupational carcinogens, and screening. Progress is still needed in areas such as weight control and physical activity. Fresh impetus for prevention and early detection will come through inter-disciplinary approaches, encompassing knowledge and tools from advances in cancer biology. Examples include mutation profiles giving clues about aetiology and biomarkers for early detection, to stratify individuals for screening or for prognosis. However, cancer prevention requires a broad perspective stretching from the sub-microscopic to the macro-political, recognizing the importance of molecular profiling and multi-sectoral engagement across urban planning, transport, environment, agriculture, economics, etc., and applying interventions that may just as easily rely on a legislative measure as on a molecule.
[Show abstract][Hide abstract] ABSTRACT: Although Epstein–Barr virus (EBV) infection is widely distributed, certain EBV-driven malignancies are geographically restricted.
EBV-associated Burkitt’s lymphoma (eBL) is endemic in children living in sub-Saharan Africa. This population is heavily exposed
to food contaminated with the mycotoxin aflatoxin B1 (AFB1). Here, we show that exposure to AFB1 in in vitro and in vivo models induces activation of the EBV lytic cycle and increases EBV load, two events that are associated with an increased
risk of eBL in vivo. AFB1 treatment leads to the alteration of cellular gene expression, with consequent activations of signaling pathways, e.g.
PI3K, that in turn mediate reactivation of the EBV life cycle. Finally, we show that AFB1 triggers EBV-driven cellular transformation
both in primary human B cells and in a humanized animal model. In summary, our data provide evidence for a role of AFB1 as
a cofactor in EBV-mediated carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Aflatoxin and fumonisin are toxic food contaminants. Knowledge about effects of their exposure and coexposure on child growth is inadequate. OBJECTIVE: We investigated the association between child growth and aflatoxin and fumonisin exposure in Tanzania. METHODS: A total of 166 children were recruited at 6-14 months of age and studied at recruitment, and at the 6th and 12th month following recruitment. Blood and urine samples were collected and analyzed for plasma aflatoxin-albumin adducts (AF-alb) using ELISA, and urinary fumonisin B-1 (UFB1) using liquid chromatography-mass spectrometry, respectively. Anthropometric measurements were taken, and growth index z-scores were computed. RESULTS: AF-alb geometric mean concentrations (95% CIs) were 4.7 (3.9, 5.6), 12.9 (9.9, 16.7), and 23.5 (19.9, 27.7) pg/mg albumin at recruitment, 6 months, and 12 months from recruitment, respectively. At these respective sampling times, geometric mean UFB1 concentrations (95% CI) were 313.9 (257.4, 382.9), 167.3 (135.4, 206.7), and 569.5 (464.5, 698.2) pg/mL urine, and the prevalence of stunted children was 44%, 55%, and 56%, respectively. UFB1 concentrations at recruitment were negatively associated with length-for-age z-scores (LAZ) at 6 months (p = 0.016) and at 12 months from recruitment (p = 0.014). The mean UFB1 of the three sampling times (at recruitment and at 6 and 12 months from recruitment) in each child was negatively associated with LAZ (p < 0.001) and length velocity (p = 0.004) at 12 months from recruitment. The negative-association between AF-alb and child growth did not reach statistical significance. CONCLUSIONS: Exposure to fumonisin alone or coexposure with aflatoxins may contribute to child growth impairment.
Full-text · Article · Oct 2014 · Environmental Health Perspectives
[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.
[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.
[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.
No preview · Article · Feb 2014 · Tropical Medicine & International Health
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is the third-most and fifth-most common cancer in men and women, in Thailand. The increasing CRC incidence and mortality can be reduced by screening and treating adenomas and early cancers. A pilot CRC screening programme using immunochemical faecal occult blood testing (iFOBT) and colonoscopy for test-positives were implemented through the routine Government Health Services in Lampang Province, to inform the acceptability, feasibility and scaling-up of screening in Thailand. This report describes the implementation, coverage and performance indicators of this project.
A target population aged 50-65 years was informed about and invited face to face to undergo CRC screening by community health workers (HWs). The HWs provided faecal sample collection kits and participants brought their samples to one of the primary health units or community hospitals where nurses performed iFOBT. iFOBT-positive persons were referred for colonoscopy at the Lampang cancer hospital, and endoscopic polypectomy/biopsies were performed according to the colonoscopic findings. Those with confirmed CRC received appropriate treatment.
Of the 127 301 target population, 62.9% were screened using iFOBT between April 2011 and November 2012. Participation was higher among women (67.8%) than men (57.8%) and lower in 50-54 year-old persons than in 60-65-year-olds. Of those screened, 873 (1.1%) were found positive; positivity was higher in men (1.2%) than in women (1.0%). To date 627 (72.0%) iFOBT-positive persons have had colonoscopy in which 3.7% had CRC and 30.6% had adenomas.
The successful implementation of the pilot CRC screening with satisfactory process measures indicate the feasibility of scaling-up organised CRC screening through existing health services in Thailand.
[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.
No preview · Article · Jan 2014 · Molecular Nutrition & Food Research
[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.
Full-text · Article · Dec 2013 · Tropical Medicine & International Health
[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.
[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.
[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.
No preview · Article · Jun 2013 · Molecular Nutrition & Food Research
[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.
No preview · Article · Feb 2013 · International Journal of Cancer
[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.