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Showing papers by "International Agency for Research on Cancer published in 2009"


Journal ArticleDOI
TL;DR: In this paper, 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).
Abstract: 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

2,349 citations


Journal ArticleDOI
TL;DR: In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.
Abstract: In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. Conclusions In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

1,019 citations


Journal ArticleDOI
TL;DR: The Working Group concluded that there is limited evidence that tobacco smoking causes breast cancer, and a causal link between parental smoking and childhood cancers has been established.
Abstract: 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

1,000 citations


Journal ArticleDOI
TL;DR: A total of 130 IDH1 mutations were detected in 321 gliomas of various histological types and biological behaviors, and all were located at amino acid residue 132.
Abstract: IDH1 encodes isocitrate dehydrogenase 1, which participates in the citric acid cycle and was recently reported to be mutated in 12% of glioblastomas. We assessed IDH1 mutations in 321 gliomas of various histological types and biological behaviors. A total of 130 IDH1 mutations was detected, and all were located at amino acid residue 132. Of these, 91% were G→A mutations (Arg→His). IDH1 mutations were frequent in low-grade diffuse astrocytomas (88%) and in secondary glioblastomas that developed through progression from low-grade diffuse or anaplastic astrocytoma (82%). Similarly, high frequencies of IDH1 mutations were found in oligodendrogliomas (79%) and oligoastrocytomas (94%). Analyses of multiple biopsies from the same patient (51 cases) showed that there were no cases in which an IDH1 mutation occurred after the acquisition of either a TP53 mutation or loss of 1p/19q, suggesting that IDH1 mutations are very early events in gliomagenesis and may affect a common glial precursor cell population. IDH1 mutations were co-present with TP53 mutations in 63% of low-grade diffuse astrocytomas and with loss of heterozygosity 1p/19q in 64% of oligodendrogliomas; they were rare in pilocytic astrocytomas (10%) and primary glioblastomas (5%) and absent in ependymomas. The frequent presence of IDH1 mutations in secondary glioblastomas and their near-complete absence in primary glioblastomas reinforce the concept that despite their histological similarities, these subtypes are genetically and clinically distinct entities.

926 citations


Journal ArticleDOI
TL;DR: In conclusion, ∼40% of vulvar, 60% of vaginal and 80% of anal carcinoma may be avoided by prophylactic vaccines against HPV16/18, and this proportion would be similar for the corresponding high‐grade lesions of the vagina and anus, but higher for VIN2/3 than for vulvar carcinoma.
Abstract: This meta-analysis investigated human papillomavirus (HPV) prevalence in vulvar, vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1-3 and carcinoma from 93 studies conducted in 4 continents and using PCR assays. Overall HPV prevalence was 67.8%, 85.3% and 40.4% among 90 VIN1, 1,061 VIN2/3 and 1,873 vulvar carcinomas; 100%, 90.1% and 69.9% among 107 VAIN1, 191 VAIN2/3 and 136 vaginal carcinomas; and 91.5%, 93.9% and 84.3% among 671 AIN1, 609 AIN2/3 and 955 anal carcinomas, respectively. HPV16 was found more frequently (>75%) and HPV18 less frequently (<10%) in HPV-positive vulvar, vaginal and anal carcinomas than in cervical carcinoma. HPV6 and 11 were common in VIN1 and AIN1, but not in VAIN1. HPV prevalence in vulvar carcinoma varied most by histological type (69.4% in warty-basaloid and 13.2% in keratinized type) and was also higher in women 60 years or younger and in studies carried out in North America. HPV prevalence in anal carcinoma was higher among women (90.8%) than men (74.9%), but no difference by gender emerged in North America. The majority of AIN2/3 derived from studies of HIV-positive individuals and/or men who have sex with men. Among AIN2/3, HIV infection was associated with higher HPV prevalence, more multiple-type infections and a relative under-representation of HPV16. In conclusion, approximately 40% of vulvar, 60% of vaginal and 80% of anal carcinoma may be avoided by prophylactic vaccines against HPV16/18. This proportion would be similar for the corresponding high-grade lesions of the vagina and anus, but higher for VIN2/3 (75%) than for vulvar carcinoma.

903 citations


Journal ArticleDOI
TL;DR: It is confirmed that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk, however, a substantial proportion of head and head cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head andneck cancer among women and among young-onset cases.
Abstract: Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter ( ψ ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk ( ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

858 citations


Journal ArticleDOI
TL;DR: Assessment of the carcinogenicity of the types of radiation previously classifi ed as “carcinogenic to humans” and to identify additional tumour sites and mechanisms of carcinogenesis establishes that in-utero exposure increases the risk of cancer at multiple sites.
Abstract: 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

803 citations


Journal ArticleDOI
TL;DR: Overall, the Working Group classifi ed arsenic and inorganic arsenic compounds as “carcinogenic to humans” (Group 1) and the organic arsenicals monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are “not classifi able’ (Group 3).
Abstract: In March, 2009, 27 scientists from eight countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of metals, arsenic, dusts, and fi bres previously classifi ed as “carcinogenic to humans” (Group 1) and to identify additional tumour sites and mechanisms of carcinogenesis (table). These assessments will be published as part C of Volume 100 of the IARC Monographs. Inhalation is the primary route of exposure to arsenic in the workplace and happens in industries such as nonferrous smelting, arsenic pro duction, wood preservation, glass manu facturing, production and application of arsenic-based pesticides, and electronics. Non-occupational exposure to arsenic is mainly through food, except in areas with high levels of arsenic in the drinking water—eg, Taiwan, Bangladesh, West Bengal (India), northern Chile, and Cordoba Province (Argentina). Epidemiological studies have shown that exposure to arsenic through inhalation or drinking-water causes cancer of the lung, skin, and urinary bladder. Evidence suggests an association between exposure to arsenic in drinking water and the development of tumours at several other sites; however, various factors prevent a conclusion. Analytical studies have provided only limited information to support an association with kidney cancer, causes of liver cancer can be diffi cult to elucidate in groups that are high-risk for hepatitis B, and data on prostate cancer and arsenic exposure are not consistent between countries. Overall, the Working Group classifi ed arsenic and inorganic arsenic compounds as “carcinogenic to humans” (Group 1). The organic arsenicals monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are the active ingredients of some herbicides and are metabolites of inorganic arsenic. On the basis of suffi cient evidence of cancer caused by DMA in experimental animals, and because MMA is extensively metabolised to DMA, both compounds are classifi ed as “possibly carcinogenic to humans” (Group 2B). Arsenobetaine and other organic arsenic compounds that are not metabolised in humans are “not classifi able” (Group 3). The Working Group reaffi rmed the classifi cation of beryllium and its compounds, cadmium and its compounds, chromium (VI) compounds, and nickel compounds as “carcinogenic to humans” (Group 1). Studies involved complex occupational exposures to a metal and its compounds, making it impossible to separately assess their carcinogenicity. Globally, an estimated 125 million people are still exposed to asbestos in the workplace. Although asbestos has been banned or restricted in most of the industrialised world, its use is increasing in parts of Asia, South America, and the former Soviet Union. Naturally occurring sources of asbestos, its use in brake linings, and deterioration of asbestos-containing products all contribute to environmental exposure worldwide. Exposure may also come from fi bres carried home on the clothing of asbestos workers. Upcoming meetings June 2–9, 2009 Radiation

783 citations


Journal ArticleDOI
TL;DR: The Working Group found limited evidence of an association between maternal exposure to painting—before and during pregnancy—and an increased risk of childhood leukaemia in the off spring.
Abstract: In October, 2009, 23 scientists from six countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of several chemical and occupational exposure circumstances previously classifi ed as ”carcinogenic to humans” (Group 1) and to identify additional tumour sites and mechanisms of carcinogenesis (table). These assessments will be published as the sixth and last part of Volume 100 of the IARC Monographs. Four aromatic amines and two related industrial processes were reaffi rmed as Group-1 carcinogens based on suffi cient evidence that they cause urinary bladder cancer in humans. The Group-1 classifi cation of dyes metabolised to benzidine and of 4,4’-methylenebis(2-chloroaniline) was based on suffi cient evidence in animal models and strong mechanistic evidence. Exposure to polycyclic aromatic hydro carbons (PAHs) causes cancers of the skin and lung in humans. Various PAH-related industries and PAHcontaining complex mixtures were confi rmed as Group-1 carcinogens. Although there are no epidemiological studies of benzo[a]pyrene, carcinogenicity in many animal species and strong mechanistic evidence justifi ed its classifi cation in Group 1. The carcinogenicity to humans of other chemicals and exposure scenarios was reaffi rmed (table). For ethylene oxide, the epidemiological evidence was limited, but there is suffi cient evidence for its carcinogenicity in rodents. Additionally, ethylene oxide is genotoxic and mutagenic in many in-vitro tests and in-vivo studies in animals, and its cytogenetic eff ects in lymphocytes of exposed workers provided strong support for its classifi cation in Group 1. Workers in the rubber-manufacturing industry have an increased risk for leukaemia, lymphoma, and cancers of the urinary bladder, lung, and stomach. Due to the diversity and com plexity of the exposures in this industry, it is diffi cult to identify causative agents, but there is strong evidence of genotoxic eff ects in these workers. The Working Group reviewed more than 100 epidemiological studies of benzene and confi rmed its carcinogenicity, with suffi cient evidence for ANLL, and limited evidence for ALL, CLL, MM, and NHL (for abbreviations, see table footnote). The Working Group also found limited evidence of an association between maternal exposure to painting—before and during pregnancy—and an increased risk of childhood leukaemia in the off spring. Dioxin (2,3,7,8-tetrachlorodibenzopara-dioxin, TCDD) was classifi ed in Group 1 in 1997, based on limited evidence of carcinogenicity in humans, For more on the IARC Monographs see http:// monographs.iarc.fr

740 citations


Journal ArticleDOI
TL;DR: IDH1 mutations are a strong predictor of a more favorable prognosis and a highly selective molecular marker of secondary glioblastomas that complements clinical criteria for distinguishing them from primary gliOBlastomas.
Abstract: Purpose: To establish the frequency of IDH1 mutations in glioblastomas at a population level, and to assess whether they allow reliable discrimination between primary ( de novo ) glioblastomas and secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma. Experimental Design: We screened glioblastomas from a population-based study for IDH1 mutations and correlated them with clinical data and other genetic alterations. Results: IDH1 mutations were detected in 36 of 407 glioblastomas (8.8%). Glioblastoma patients with IDH1 mutations were younger (mean, 47.9 years) than those with EGFR amplification (60.9 years) and were associated with significantly longer survival (mean, 27.1 versus 11.3 months; P IDH1 mutations were frequent in glioblastomas diagnosed as secondary (22 of 30; 73%), but rare in primary glioblastomas (14 of 377; 3.7%: P IDH1 mutations as genetic marker of secondary glioblastoma corresponded to the respective clinical diagnosis in 95% of cases. Glioblastomas with IDH1 mutation diagnosed as primary had clinical and genetic profiles similar to those of secondary glioblastomas, suggesting that they may have rapidly progressed from a less malignant precursor lesion that escaped clinical diagnosis and were thus misclassified as primary. Conversely, glioblastomas without IDH1 mutations clinically diagnosed as secondary typically developed from anaplastic rather than low-grade gliomas, suggesting that at least some were actually primary glioblastomas, that may have been misclassified, possibly due to histologic sampling error. Conclusion: IDH1 mutations are a strong predictor of a more favorable prognosis and a highly selective molecular marker of secondary glioblastomas that complements clinical criteria for distinguishing them from primary glioblastomas. (Clin Cancer Res 2009;15(19):6002–7)

637 citations


Journal ArticleDOI
TL;DR: Steady downward trends persist in gastric cancer mortality worldwide even in middle aged population, and hence further appreciable declines are likely in the near future.
Abstract: Until the mid-1990s, gastric cancer has been the first cause of cancer death worldwide, although rates had been declining for several decades and gastric cancer has become a relatively rare cancer in North America and in most Northern and Western Europe, but not in Eastern Europe, Russia and selected areas of Central and South America or East Asia. We analyzed gastric cancer mortality in Europe and other areas of the world from 1980 to 2005 using joinpoint regression analysis, and provided updated site-specific incidence rates from 51 selected registries. Over the last decade, the annual percent change (APC) in mortality rate was around -3, -4% for the major European countries. The APC were similar for the Republic of Korea (APC = -4.3%), Australia (-3.7%), the USA (-3.6%), Japan (-3.5%), Ukraine (-3%) and the Russian Federation (-2.8%). In Latin America, the decline was less marked, but constant with APC around -1.6% in Chile and Brazil, -2.3% in Argentina and Mexico and -2.6% in Colombia. Cancers in the fundus and pylorus are more common in high incidence and mortality areas and have been declining more than cardia gastric cancer. Steady downward trends persist in gastric cancer mortality worldwide even in middle aged population, and hence further appreciable declines are likely in the near future.

Journal ArticleDOI
Laufey T. Amundadottir1, Peter Kraft2, Rachael Z. Stolzenberg-Solomon1, Charles S. Fuchs2, Gloria M. Petersen3, Alan A. Arslan4, H. Bas Bueno-de-Mesquita5, Myron D. Gross6, Kathy J. Helzlsouer7, Eric J. Jacobs8, Andrea Z. LaCroix9, Wei Zheng10, Demetrius Albanes1, William R. Bamlet3, Christine D. Berg1, Franco Berrino, Sheila Bingham11, Julie E. Buring2, Paige M. Bracci12, Federico Canzian13, Françoise Clavel-Chapelon14, Sandra Clipp15, Michelle Cotterchio16, Mariza de Andrade3, Eric J. Duell17, John W. Fox18, Steven Gallinger16, J. Michael Gaziano19, J. Michael Gaziano2, Edward Giovannucci2, Michael Goggins15, Carlos A. González, Göran Hallmans20, Susan E. Hankinson2, Manal Hassan21, Elizabeth A. Holly12, David J. Hunter2, Amy K. Hutchinson1, Amy K. Hutchinson22, Rebecca D. Jackson23, Kevin B. Jacobs1, Kevin B. Jacobs22, Mazda Jenab17, Rudolf Kaaks13, Alison P. Klein15, Charles Kooperberg9, Robert C. Kurtz24, Donghui Li21, Shannon M. Lynch1, Margaret T. Mandelson25, Margaret T. Mandelson9, Robert R. McWilliams3, Julie B. Mendelsohn1, Dominique S. Michaud2, Dominique S. Michaud26, Sara H. Olson24, Kim Overvad27, Alpa V. Patel8, Petra H.M. Peeters26, Petra H.M. Peeters5, Aleksandar Rajkovic28, Elio Riboli26, Harvey A. Risch29, Xiao-Ou Shu10, Gilles Thomas1, Geoffrey S. Tobias1, Dimitrios Trichopoulos2, Dimitrios Trichopoulos30, Stephen K. Van Den Eeden31, Jarmo Virtamo32, Jean Wactawski-Wende33, Brian M. Wolpin2, Herbert Yu29, Kai Yu1, Anne Zeleniuch-Jacquotte4, Stephen J. Chanock1, Patricia Hartge1, Robert N. Hoover1 
TL;DR: In this paper, a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide, was conducted, where 558,542 SNPs were genotyped in 1,896 individuals and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study.
Abstract: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Journal ArticleDOI
TL;DR: In this paper, the authors have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays, which are based on the data from various large screening studies and can be used to guide the translation of highrisk HPV testing into clinical practice by setting standards of test performance and characteristics.
Abstract: Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays.

Journal ArticleDOI
TL;DR: A lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma, and previously reported association signals on 15q25 and 6p21 were refined, but no additional loci reached genome-wide significance.
Abstract: Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13–1.33, p = 3.02 × 10−7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17–1.31, p = 3.74 × 10−14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.

Laufey T. Amundadottir1, Peter Kraft2, Rachael Z. Stolzenberg-Solomon1, Charles S. Fuchs2, Gloria M. Petersen3, Alan A. Arslan4, H. Bas Bueno-de-Mesquita5, Myron D. Gross6, Kathy J. Helzlsouer7, Eric J. Jacobs8, Andrea Z. LaCroix9, Wei Zheng10, Demetrius Albanes1, William R. Bamlet3, Christine D. Berg1, Franco Berrino, Sheila Bingham11, Julie E. Buring2, Paige M. Bracci12, Federico Canzian13, Françoise Clavel-Chapelon14, Sandra Clipp15, Michelle Cotterchio16, Mariza de Andrade3, Eric J. Duell17, John W. Fox18, Steven Gallinger16, J. Michael Gaziano2, J. Michael Gaziano19, Edward Giovannucci2, Michael Goggins15, Carlos A. González, Göran Hallmans20, Susan E. Hankinson2, Manal Hassan21, Elizabeth A. Holly12, David J. Hunter2, Amy K. Hutchinson1, Amy K. Hutchinson22, Rebecca D. Jackson23, Kevin B. Jacobs1, Kevin B. Jacobs22, Mazda Jenab17, Rudolf Kaaks13, Alison P. Klein15, Charles Kooperberg9, Robert C. Kurtz24, Donghui Li21, Shannon M. Lynch1, Margaret T. Mandelson25, Margaret T. Mandelson9, Robert R. McWilliams3, Julie B. Mendelsohn1, Dominique S. Michaud26, Dominique S. Michaud2, Sara H. Olson24, Kim Overvad27, Alpa V. Patel8, Petra H.M. Peeters5, Petra H.M. Peeters26, Aleksandar Rajkovic28, Elio Riboli26, Harvey A. Risch29, Xiao-Ou Shu10, Gilles Thomas1, Geoffrey S. Tobias1, Dimitrios Trichopoulos30, Dimitrios Trichopoulos2, Stephen K. Van Den Eeden31, Jarmo Virtamo32, Jean Wactawski-Wende33, Brian M. Wolpin2, Herbert Yu29, Kai Yu1, Anne Zeleniuch-Jacquotte4, Stephen J. Chanock1, Patricia Hartge1, Robert N. Hoover1 
01 Jan 2009
TL;DR: An association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 is identified, consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreaticcancer than those with groups A or B.
Abstract: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Journal ArticleDOI
TL;DR: It is shown that PRIMA-1 is converted to compounds that form adducts with thiols in mutant p53, which is sufficient to induce apoptosis in tumor cells and facilitate the design of more potent and specific mutant p 53-targeting anticancer drugs.

Journal ArticleDOI
TL;DR: A large fraction of lung cancers occurring in never smokers cannot be definitively associated with established environmental risk factors, highlighting the need for additional epidemiologic research in this area.
Abstract: More than 161,000 lung cancer deaths are projected to occur in the United States in 2008. Of these, an estimated 10 to 15% will be caused by factors other than active smoking, corresponding to 16,000 to 24,000 deaths annually. Thus lung cancer in never smokers would rank among the most common causes of cancer mortality in the United States if considered as a separate category. Slightly more than half of the lung cancers caused by factors other than active smoking occur in never smokers. As summarized in the accompanying article, lung cancers that occur in never smokers differ from those that occur in smokers in their molecular profile and response to targeted therapy. These recent laboratory and clinical observations highlight the importance of defining the genetic and environmental factors responsible for the development of lung cancer in never smokers. This article summarizes available data on the clinical epidemiology of lung cancer in never smokers, and several environmental risk factors that population-based research has implicated in the etiology of these cancers. Primary factors closely tied to lung cancer in never smokers include exposure to known and suspected carcinogens including radon, second-hand tobacco smoke, and other indoor air pollutants. Several other exposures have been implicated. However, a large fraction of lung cancers occurring in never smokers cannot be definitively associated with established environmental risk factors, highlighting the need for additional epidemiologic research in this area.

Journal ArticleDOI
TL;DR: An approach recently taken by the World Health Organization International Agency for Research on Cancer (IARC) Monographs Working Group to re-assess the carcinogenicity of different HPV types is described.
Abstract: Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC) Monographs Working Group to re-assess the carcinogenicity of different HPV types.

Journal ArticleDOI
TL;DR: The current status of genetic alterations and signaling pathways operative in the evolution of astrocytic and oligodendroglial tumors is summarized.
Abstract: Gliomas are the most common primary brain tumors. They account for more than 70% of all neoplasms of the central nervous system and vary considerably in morphology, location, genetic alterations, and response to therapy. Most frequent and malignant are glioblastomas. The vast majority (>90%) develops rapidly after a short clinical history and without evidence of a less malignant precursor lesion (primary or de novo glioblastoma). Secondary glioblastomas develop more slowly through progression from low-grade or anaplastic astrocytoma. These glioblastoma subtypes constitute distinct disease entities that affect patients of different age, develop through distinct genetic pathways, show different RNA and protein expression profiles, and may differ in their response to radio- and chemotherapy. Recently, isocitrate dehydrogenase 1 (IDH1) mutations have been identified as a very early and frequent genetic alteration in the pathway to secondary glioblastomas as well as that in oligodendroglial tumors, providing the first evidence that low-grade astrocytomas and oligodendrogliomas may share common cells of origin. In contrast, primary glioblastomas very rarely contain IDH1 mutations, suggesting that primary and secondary glioblastomas may originate from different progenitor cells, despite the fact that they are histologically largely indistinguishable. In this review, we summarize the current status of genetic alterations and signaling pathways operative in the evolution of astrocytic and oligodendroglial tumors.

Journal ArticleDOI
TL;DR: This review emphasizes the need to identify new dietary biomarkers and highlights the emerging field of nutritional metabonomics as an analytical method to assess metabolic profiles as measures of dietary exposures and indicators of dietary patterns, dietary changes or effectiveness of dietary interventions.
Abstract: Modern epidemiology suggests a potential interactive association between diet, lifestyle, genetics and the risk of many chronic diseases. As such, many epidemiologic studies attempt to consider assessment of dietary intake alongside genetic measures and other variables of interest. However, given the multi-factorial complexities of dietary exposures, all dietary intake assessment methods are associated with measurement errors which affect dietary estimates and may obscure disease risk associations. For this reason, dietary biomarkers measured in biological specimens are being increasingly used as additional or substitute estimates of dietary intake and nutrient status. Genetic variation may influence dietary intake and nutrient metabolism and may affect the utility of a dietary biomarker to properly reflect dietary exposures. Although there are many functional dietary biomarkers that, if utilized appropriately, can be very informative, a better understanding of the interactions between diet and genes as potentially determining factors in the validity, application and interpretation of dietary biomarkers is necessary. It is the aim of this review to highlight how some important biomarkers are being applied in nutrition epidemiology and to address some associated questions and limitations. This review also emphasizes the need to identify new dietary biomarkers and highlights the emerging field of nutritional metabonomics as an analytical method to assess metabolic profiles as measures of dietary exposures and indicators of dietary patterns, dietary changes or effectiveness of dietary interventions. The review will also touch upon new statistical methodologies for the combination of dietary questionnaire and biomarker data for disease risk assessment. It is clear that dietary biomarkers require much further research in order to be better applied and interpreted. Future priorities should be to integrate high quality dietary intake information, measurements of dietary biomarkers, metabolic profiles of specific dietary patterns, genetics and novel statistical methodology in order to provide important new insights into gene-diet-lifestyle-disease risk associations.

Book ChapterDOI
TL;DR: Significant correlation between G:C --> A:T transitions in the TP53 gene and promoter methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene in glio-mas have been reported in several studies, suggesting the possible involvement of O6-methylguAnine DNA adducts, which may be produced by exogenous or endogenous alkylating agents in the development of gliomas.
Abstract: Gliomas account for more than 70% of all brain tumors, and of these, glioblastoma is the most frequent and malignant histologic type (World Health Organization [WHO] grade IV). There is a tendency toward a higher incidence of gliomas in highly developed, industrialized countries. Some reports indicate that Caucasians have a higher incidence than African or Asian populations. With the exception of pilocytic astrocytomas (WHO grade I), the prognosis of glioma patients is still poor. Fewer than 3% of glioblastoma patients are still alive at 5 years after diagnosis, older age being the most significant and consistent prognostic factor of poorer outcome. Gliomas are components of several inherited tumor syndromes, but the prevalence of these syndromes is very low. Many environmental and lifestyle factors including several occupations, environmental carcinogens, and diet have been reported to be associated with an elevated glioma risk, but the only factor unequivocally associated with an increased risk is therapeutic X-irradiation. In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumors, often within 10 years after therapy. Significant correlation between G:C --> A:T transitions in the TP53 gene and promoter methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene in glio-mas have been reported in several studies, suggesting the possible involvement of O6-methylguanine DNA adducts, which may be produced by exogenous or endogenous alkylating agents in the development of gliomas.

Journal ArticleDOI
TL;DR: Alcohol accounts for most of the large fluctuations in Russian mortality, and alcohol and tobacco account for the large difference in adult mortality between Russia and western Europe.

Journal ArticleDOI
TL;DR: The incidence of liver cancer is high in all low-resource regions of the world, with the exception of Northern Africa and Western Asia and the increased prevalence of overweight and obesity likely contributes to it.

Journal ArticleDOI
TL;DR: The presence or absence of human papillomavirus in patients with squamous cell carcinoma of the head and neck is a new parameter for prediction of long-term outcome of cancer of the oral cavity and of the oropharynx.
Abstract: Purpose of reviewTo review the most recent epidemiological studies on head and neck cancer and changes in knowledge about risk factors. The main review concerned the squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx.Recent findingsOverall, the incidence of head and neck

Journal ArticleDOI
TL;DR: Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration.
Abstract: Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (> or =30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (> or =50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (> or =40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.

Journal ArticleDOI
TL;DR: The nationwide cancer statistics in this paper will provide essential data for cancer research and evidence-based health policy in Korea and notable improvement has been observed in the 5-yr relative survival rates for most major cancers and for all cancer combined, with the exception of pancreatic cancer.
Abstract: Cancer has been the most common cause of death in Korea since 1983 and is a major public health concern. This paper overviews the nationwide cancer statistics, including incidence, mortality, and survival rates, and their trends in Korea. In 2005, 142,610 new cancer cases and 65,117 cancer deaths occurred in Korea. The incidence rate for all cancer combined increased by 2.6% annually from 1999 to 2005. Significant increases have occurred in the incidence of colorectal, thyroid, female breast, and prostate cancers. The number of cancer deaths has increased over the past two decades, due mostly to population aging, while the age-standardized mortality rates have decreased in both men and women since 2002. Notable improvement has been observed in the 5-yr relative survival rates for most major cancers and for all cancer combined, with the exception of pancreatic cancer. The nationwide cancer statistics in this paper will provide essential data for evidence-based decisions in the national cancer control program in Korea.

Journal ArticleDOI
TL;DR: It is suggested that a high consumption of fruit and vegetables is associated with a reduced risk of CRC, especially of colon cancer, and this effect may depend on smoking status.

Journal ArticleDOI
27 Mar 2009-BMJ
TL;DR: Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer, and a strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk.
Abstract: Objective To investigate the association between tea drinking habits in Golestan province, northern Iran, and risk of oesophageal squamous cell carcinoma. Design Population based case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk were measured among healthy participants in a cohort study. Setting Golestan province, northern Iran, an area with a high incidence of oesophageal squamous cell carcinoma. Participants 300 histologically proved cases of oesophageal squamous cell carcinoma and 571 matched neighbourhood controls in the case-control study and 48 582 participants in the cohort study. Main outcome measure Odds ratio of oesophageal squamous cell carcinoma associated with drinking hot tea. Results Nearly all (98%) of the cohort participants drank black tea regularly, with a mean volume consumed of over one litre a day. 39.0% of participants drank their tea at temperatures less than 60°C, 38.9% at 60-64°C, and 22.0% at 65°C or higher. A moderate agreement was found between reported tea drinking temperature and actual temperature measurements (weighted κ 0.49). The results of the case-control study showed that compared with drinking lukewarm or warm tea, drinking hot tea (odds ratio 2.07, 95% confidence interval 1.28 to 3.35) or very hot tea (8.16, 3.93 to 16.9) was associated with an increased risk of oesophageal cancer. Likewise, compared with drinking tea four or more minutes after being poured, drinking tea 2-3 minutes after pouring (2.49, 1.62 to 3.83) or less than two minutes after pouring (5.41, 2.63 to 11.1) was associated with a significantly increased risk. A strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk (weighted κ 0.68). Conclusion Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer. Reza Malekzadeh and other authors of this population based case-control study talk about the effect of tea drinking and oesophageal cancer in Golestan province, northern Iran

Journal ArticleDOI
TL;DR: At present, the only recognized measures for reducing TC risk is to avoid ionizing radiation and iodine deficiency, particularly in childhood and young women, and to increase vegetable consumption.
Abstract: The present review summarizes epidemiological evidence on risk factors for thyroid cancer (TC), in particular, nutritional factors. Searches of articles on the issue were conducted using MEDLINE. Exposure to ionizing radiation, particularly during childhood, is the best-established risk factor for TC. There is also a strong association with history of benign nodules/adenoma or goiter. Iodine deficiency may induce an increasing incidence of benign thyroid conditions, but very high iodine intake also affects thyroid function and, possibly, TC risk. Among dietary factors, fish—the major natural source of iodine in human diet—is not consistently related to TC risk. High intake of cruciferous vegetables shows a weak inverse association with TC. Among other food groups, vegetables other than cruciferous are the only food group showing a favorable effect on TC, with an approximate 20% reduction in risk for subjects with the highest consumption. No effect on TC risk of alcohol, coffee, or other food-groups/nutrients emerged. Height and weight at diagnosis show a moderate positive association with TC risk. At present, the only recognized measures for reducing TC risk is to avoid ionizing radiation and iodine deficiency, particularly in childhood and young women, and to increase vegetable consumption.

Journal ArticleDOI
TL;DR: Overall, the available results strongly suggest that high‐temperature beverage drinking increases the risk of EC.
Abstract: Coffee, tea and mate may cause esophageal cancer (EC) by causing thermal injury to the esophageal mucosa. If so, the risk of EC attributable to thermal injury could be large in populations in which these beverages are commonly consumed. In addition, these drinks may cause or prevent EC via their chemical constituents. Therefore, a large number of epidemiologic studies have investigated the association of an indicator of amount or temperature of use of these drinks or other hot foods and beverages with risk of EC. We conducted a systematic review of these studies and report the results for amount and temperature of use separately. By searching PubMed and the ISI, we found 59 eligible studies. For coffee and tea, there was little evidence for an association between amount of use and EC risk; however, the majority of studies showed an increased risk of EC associated with higher drinking temperature which was statistically significant in most of them. For mate drinking, the number of studies was limited, but they consistently showed that EC risk increased with both amount consumed and temperature, and these 2 were independent risk factors. For other hot foods and drinks, over half of the studies showed statistically significant increased risks of EC associated with higher temperature of intake. Overall, the available results strongly suggest that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data and results should be reported by histological subtypes of EC.