The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

/pdf/global-cancer-statistics-49zjx478re.pdf

Global cancer statistics

Viral hepatitis in all its forms is a major public health problem throughout the world, affecting several hundreds of millions of people. Viral hepatitis is a cause of considerable morbidity and mortality both from acute infection and chronic sequelae which include, in the case of hepatitis B, C and D, chronic active hepatitis and cirrhosis. Hepatocellular carcinoma, which is one of the 10 commonest cancers worldwide, is closely associated with hepatitis B and, at least in some regions of the world, with hepatitis C virus. This timely monograph is a distillation of knowledge of hepatitis B, C and D, based on a review of 1000 studies by a small group of scientists. (It is interesting to note in passing that some 5000 papers on viral hepatitis are published annually in the world literature.) The epidemiological, clinical and experimental data on the association between infection with hepatitis B virus and primary liver cancer in humans are reviewed in a readable and succinct format. The available information on hepatitis C and progression to chronic infection is also evaluated and it is concluded (perhaps a little prematurely) that hepatitis C virus is carcinogenic. However, it is concluded that hepatitis D virus, an unusual virus with a number of similarities to certain plant viral satellites and viroids, cannot be classified as a human carcinogen. There are some minor criticisms: there are few illustrations and some complex tabulations (for example, Table 6) and no subject index. A cumulative cross index to IARC Monographs is of little value and occupies nearly 30 pages. This small volume is a useful addition to the overwhelming literature on viral hepatitis, and the presentation is similar to the excellent World Health Organisation Technical Reports series on the subject published in the past. It is strongly recommended as a readable up-to-date summary of a complex subject; and at a cost of 65 Sw.fr (approximately £34) is excellent value. A J ZUCKERMAN

https://jcp.bmj.com/content/jclinpath/48/7/691.1.full.pdf

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61766-8.pdf

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)60746-7.pdf

Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders.

The Environmental Protection Agency (EPA) provides access to information on a variety of topics related to the environment and strives to inform citizens of health risks. The EPA also has an extensive library network that consists of 26 libraries throughout the United States, which provide access to a plethora of information to EPA employees, scientists, and researchers. The EPA implemented a reorganization project to digitize their materials so they would be more accessible to a wider range of users, but this plan was drastically accelerated when the EPA was threatened with a budget cut. It chose to close and reduce the hours and services of some of their libraries. As a result, the agency was accused of denying users the “right to know” by making information unavailable, not providing an adequate strategic plan, and discarding vital materials. This case study explores the background of the digitization project, the practices implemented, and the critiques of the project.

/pdf/the-environmental-protection-agency-3gx4opzrjm.pdf

The Environmental Protection Agency

In February, 2009, 36 scientists from 16 countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of the biological agents classifi ed as “carcinogenic to humans” (Group 1) and to identify additional tumour sites and mechanisms of carcinogenesis (tables 1 and 2). These assessments will be published as part B of Volume 100 of the IARC Monographs. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect, res pectively, over 300 million and 170 million people worldwide, mainly in Asia and Africa. Chronic infection with these viruses is known to cause hepatocellular carcinoma. Suffi cient evidence is available to conclude that chronic infection with HCV can also cause non-Hodgkin lymphoma, especially B-cell lymphoma. In an inter vention study, patients with HCV infection and splenic lymphoma who were given the antiviral agent, interferon, showed regression of the lymphoma. Epstein–Barr virus (EBV) infects almost everyone and causes several types of cancer, including nasopharyngeal carcinoma, one of the most common cancers in southeastern Asia, and Burkitt’s lymphoma in children in Africa. New evidence points to a role for EBV in 5–10% of gastric carcinomas worldwide. EBV-positive gastric carcinoma develops early in life and has distinct histopathology, therefore it might belong to a separate clinical entity. In this subset of gastric tumours, presence of the viral genome in a monoclonal form and expression of EBV-transforming proteins are strong evidence for the involvement of EBV. Data from 22 cohort studies and 80 case–control studies show an association between Kaposi’s sarcoma herpes virus (KSHV) and Kaposi’s sarcoma, with relative risks higher than 10. Most studies are of transplant recipients and people infected with HIV-1. In both patients who are and are not infected with HIV-1, risk of Kaposi’s sarcoma increases relative to increasing titre of antibodies directed against KSHV, which are markers of the viral load. Evidence is suffi cient to show that KSHV causes primary eff usion lymphoma, a rare subgroup of B-cell non-Hodgkin lymphoma. Mechanistic data support an oncogenic role for KSHV in Kaposi’s sarcoma and in primary eff usion lymphoma—in individuals who are immunocompromised and in those apparently immunocompetent. KSHV is also associated with multicentric Castleman’s disease. Individuals who are infected with HIV-1 have a high risk of cancer. HIV-1 infection, mainly through immunosuppression, leads to increased replication of oncogenic viruses such as EBV and KSHV. Although antiretroviral therapy lowers the risk of many cancers associated with HIV-1, risks remain high. Cervical cancer is caused by types of human papillomavirus (HPV) that belong to a few phylogenetically related “high-risk” species (alpha-5, 6, 7, 9, 11) of the mucosotropic alpha genus. The types found most frequently in cervical cancer (HPV-16, 18, 31, 33, 35, 45, 52, 58) and four types less constantly found (HPV-39, 51, 56, 59) were classifi ed in

A review of human carcinogens--Part B: biological agents

www.thelancet.com/oncology Vol 10 November 2009 1033 In October, 2009, 30 scientists from 10 countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of tobacco, areca nut, alcohol, coal smoke, and saltpreserved fi sh, and to identify additional tumour sites (table) and mechanisms of carcinogenesis. These assessments will be published as part E of Volume 100 of the IARC Monographs. Tobacco smoking is the single largest cause of cancer worldwide. More than 1 billion people around the world are current smokers. New evidence con tinues to add to the extensive list of tobacco-related cancers (table); there is now suffi cient evidence that tobacco smoking causes cancer of the colon and of the ovary. More than 150 epi demiological studies of tobacco smoking and breast cancer were reviewed. Large cohort studies published since 2002 consistently show a small positive association (relative risks 1·1–1·3). Many chemicals in tobacco smoke cause mammarygland tumours in animals, and these carcinogens are stored in breast adipose tissue in women; therefore, the Working Group concluded that there is limited evidence that tobacco smoking causes breast cancer. A causal link between parental smoking and childhood cancers has been established. Four recent studies showed that children born of parents who smoke (father, mother, or both, including the preconception period and pregnancy) are at signifi cantly higher risk of hepatoblastoma, a rare embryonic cancer. The UK Childhood Cancer Study reported a relative risk of 1·86 for paternal smoking only and 2·02 for maternal smoking only, increasing to 4·74 (95% CI 1·68–13·35) when both parents smoke. For childhood leukaemia, a meta-analysis reported an associ ation with paternal smoking before pregnancy (summary relative risk 1·12, 1·04–1·21). Second-hand smoke causes lung cancer. There is now limited evidence for an association with cancers of the larynx and the pharynx, whereas evidence for female breast cancer remains inconclusive. Since secondhand smoke contains most of the constituents of mainstream smoke, it might also be associated with other cancer sites. Many types of smokeless tobacco are marketed and all contain nicotine and nitrosamines. Hundreds of millions of people use smokeless tobacco, mainly in India and southeast Asia, but also in Sweden and the USA. Earlier fi ndings showed a causal association between use of smokeless tobacco and cancers of the oral cavity and pancreas, and there is now suffi cient evidence for cancer of the oesophagus. All of the forms of tobacco discussed above induce malignant tumours in laboratory animals. Among the many carcinogens present in tobacco are nitrosamines, including the tobaccospecifi c nitrosamines 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone Special Report: Policy A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fi sh

A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish.

In October, 2007, 24 scientists from ten countries met at the International Agency for Research on Cancer (IARC), Lyon, France, to assess the carcinogenicity of shift-work, painting, and fi re-fi ghting. These assessments will be published as volume 98 of the IARC Monographs. About 15–20% of the working population in Europe and the USA is engaged in shift-work that involves nightwork, which is most prevalent (above 30%) in the health-care, industrial manufactur ing, mining, transport, communication, leisure, and hospitality sectors. Among the many diff erent patterns of shiftwork, those including nightwork are the most disruptive for the circadian clock. Six of eight epidemiological studies from various geographical regions, most notably two independent cohort studies of nurses engaged in shiftwork at night, have noted a modestly increased risk of breast cancer in long-term employees compared with those who are not engaged in shiftwork at night. These studies are limited by potential confounding and inconsistent defi nitions of shiftwork, with several focused on a single profession. The incidence of breast cancer was also modestly increased in most cohorts of female fl ight attendants, who also experience circadian disruption by frequently crossing time zones. Limitations of studies in these fl ight attendants include the potential for detection bias, proxy measures of exposure, and potential uncontrolled confounding by reproductive factors and cosmic radiation. Several diff erent rodent models have been used to test the eff ect of disruption of the circadian system on tumour development. More than 20 studies investigated the eff ect of constant light, dim light at night, simulated chronic jet lag, or circadian timing of carcinogens, and most showed a major increase in tumour incidence. No clear eff ect was seen for light pulses at night or constant darkness. A similar number of studies investigated the eff ect of reduced nocturnal melatonin concentrations or removal of the pineal gland (where melatonin is produced) in tumour development and most showed increases in the incidence or growth of tumours. Exposure to light at night disturbs the circadian system with alterations of sleep-activity patterns, suppression of melatonin production, and de regul ation of circadian genes involved in cancer-related pathways. Inactivation of the circadian Period gene, Per2, promotes tumour develop ment in mice, and in human breast and endo metrial tumours, the expression of PERIOD genes is inhibited. In animals, melatonin suppression can lead to changes in the gonadotrophin axis. In humans, sleep deprivation and the ensuing melatonin suppression lead to immunodefi ciency. For example, sleep deprivation suppresses natural killer-cell activity and changes the T-helper 1/T-helper 2 cytokine balance, reducing cellular immune defence and surveillance. On the basis of “limited evidence in humans for the carcinogenicity of shift-work that involves nightwork”, and “suffi cient evidence in experimental animals for the carcinogenicity of light during the daily dark period (biological night)”, the Working Group concluded that “shift-work that involves circadian disruption is probably carcinogenic to humans” (Group 2A). Painters are potentially exposed to many chemicals used as pigments, extenders, binders, solvents, and additives. Painters can also be exposed to other workplace hazards, such as asbestos or crystalline silica. Cohort and linkage studies of painters have shown consistent and signifi cant increases in lung cancer compared with the general population. No information on tobacco smoking was available in the cohort studies; however, the increases are comparable to results from many case–control studies that controlled for smoking. A meta-analysis by the Working Group of all independent studies, including two recent large studies, showed a signifi cant excess risk of about 20% overall, and of 50% when the analysis was restricted to smoking-adjusted estimates from population-based case–control studies. Increased mortality from mesothelioma was consistently noted. Similarly, cohort and linkage studies showed consistent 20–25% increases in the occurrence of urinary bladder cancer in painters, and similar increases were noted in case– control studies that controlled for smoking. Although fi ndings for lymphatic and haemopoietic cancers in painters were inconsistent, four of fi ve case– control studies reported signifi cant increases in childhood leukaemia associated with maternal exposure to paint. The risks tended to be greater when mothers were exposed before or during, rather than after, pregnancy, and two studies showed some evidence of an increasing risk with increasing exposure. Upcoming meetings February 5–12, 2008 Industrial and cosmetic dyes and related exposures

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045%2807%2970373-X.pdf

Carcinogenicity of shift-work, painting, and fire-fighting.

In February, 2007, 26 scientists from 15 countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to reassess the carcino-genicity of alcoholic beverages and of ethyl carbamate (urethane), a frequent contaminant of fermented foods and beverages. These assessments will be published as volume 96 of the IARC Monographs.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(07)70099-2.pdf

Carcinogenicity of alcoholic beverages

In June 2009, 20 scientists from nine countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of the types of radiation previously classified as “carcinogenic to humans” (Group 1) and to identify additional tumour sites and mechanisms of carcinogenesis (table and panel). These assessments will be published as part D of Volume 100 of the IARC Monographs. Alpha particles, consisting of two protons and two neutrons, are a densely ionising type of radiation with low capacity to penetrate living tissue (less than 0·1 mm). Beta particles are electrons or positrons that are less ionising, but more penetrating (up to a few milimetres). The health hazards resulting from radionuclides that emit these particles largely occur after internal deposition. Epidemiological evidence shows a number of radionuclides that emit alpha or beta particles increase cancer risks at several anatomical sites (table). The Working Group reaffirmed the carcinogenicity of internally deposited radionuclides that emit alpha or beta particles (Group 1). After the Chernobyl accident, a sharp increase in the risk of thyroid cancer was found with exposure to radioiodines, particularly iodine-131, during childhood and adolescence. This increased risk might be due to higher milk intake per unit of body weight among children; a higher thyroid dose per unit of iodine-131 intake from milk; a higher susceptibility per unit of thyroid dose; or a combination of these. Radon exposure occurs mainly through contamination of indoor air by radon released from soil and building materials. Combined analyses of case–control studies now estimate that residential exposure to radon gas is the leading cause of lung cancer after tobacco smoke (8–15% attributable risk in Europe and North America). X-rays and gamma-rays are sparsely ionising electromagnetic radiation that penetrate living tissue, typically producing fast electrons that deposit energy, resulting in tissue damage. Extensive study of atomicbomb survivors shows increased cancer risks at multiple anatomical sites. Current evidence adds to the list of tumours caused by x-rays and gamma-rays (table), and also establishes that in-utero exposure increases the risk of cancer at multiple sites. The Working Group reaffirmed the carcinogenicity of x-radiation and gamma-radiation (Group 1). Neutrons are produced by nuclear reactions and are a main component of cosmic radiation. They are highly penetrating and interact with the traversed tissue, producing protons, other charged particles, and gamma-radiation. Epidemiological evidence is inadequate to assess the carcinogenicity of neutrons, because of co-exposures to other types of radiation. However, the evidence of cancer in experimental animals is sufficient, and mechanistic data show that neutrons transfer their energy in clusters of ionising events— resulting in similar, but more severe, local damage than that induced by x-rays or gamma-rays. On the basis of this evidence, the Working Group reaffirmed the carcinogenicity of neutron radiation (Group 1). Each type of ionising radiation (panel) transfers energy in the form of highly structured tracks of Upcoming meetings Sept 29–Oct 6, 2009 Lifestyle Factors

Vincent Cogliano

Papers

A review of human carcinogens--Part B: biological agents

A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish.

Carcinogenicity of shift-work, painting, and fire-fighting.

Carcinogenicity of alcoholic beverages

A review of human carcinogens--part D: radiation.