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Summary Background Cancer survival varies widely between countries. The CONCORD study provides survival estimates for 1·9 million adults (aged 15–99 years) diagnosed with a first, primary, invasive cancer of the breast (women), colon, rectum, or prostate during 1990–94 and followed up to 1999, by use of individual tumour records from 101 population-based cancer registries in 31 countries on five continents. This is, to our knowledge, the first worldwide analysis of cancer survival, with standard quality-control procedures and identical analytic methods for all datasets. Methods To compensate for wide international differences in general population (background) mortality by age, sex, country, region, calendar period, and (in the USA) ethnic origin, we estimated relative survival, the ratio of survival noted in the patients with cancer, and the survival that would have been expected had they been subject only to the background mortality rates. 2800 life tables were constructed. Survival estimates were also adjusted for differences in the age structure of populations of patients with cancer. Findings Global variation in cancer survival was very wide. 5-year relative survival for breast, colorectal, and prostate cancer was generally higher in North America, Australia, Japan, and northern, western, and southern Europe, and lower in Algeria, Brazil, and eastern Europe. CONCORD has provided the first opportunity to estimate cancer survival in 11 states in USA covered by the National Program of Cancer Registries (NPCR), and the study covers 42% of the US population, four-fold more than previously available. Cancer survival in black men and women was systematically and substantially lower than in white men and women in all 16 states and six metropolitan areas included. Relative survival for all ethnicities combined was 2–4% lower in states covered by NPCR than in areas covered by the Surveillance Epidemiology and End Results (SEER) Program. Age-standardised relative survival by use of the appropriate race-specific and state-specific life tables was up to 2% lower for breast cancer and up to 5% lower for prostate cancer than with the census-derived national life tables used by the SEER Program. These differences in population coverage and analytical method have both contributed to the survival deficit noted between Europe and the USA, from which only SEER data have been available until now. Interpretation Until now, direct comparisons of cancer survival between high-income and low-income countries have not generally been available. The information provided here might therefore be a useful stimulus for change. The findings should eventually facilitate joint assessment of international trends in incidence, survival, and mortality as indicators of cancer control. Funding Centers for Disease Control and Prevention (Atlanta, GA, USA), Department of Health (London, UK), Cancer Research UK (London, UK).

© 2015 Allemani et al. Open Access article distributed under the terms of CC BY. Background Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. Methods Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. Interpretation International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. Funding Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR 5 2.50; 95% CI 5 2.02-3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR 5 1.61; 95% CI 5 1.13-2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels. © 2014 UICC.

Background The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case-control studies conducted in regions with differing Background risks of esophageal cancer. Methods We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case-control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided. ResultsWe found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P =. 023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P

Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the eff ectiveness of health systems, and to inform global policy on cancer control. Methods Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15–99 years) and 75 000 children (age 0–14 years) diagnosed with cancer during 1995–2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005–09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15–19% in North America, and as low as 7–9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10–20% between 1995–99 and 2005–09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995–99 and 2005–09 have generally been slight. For women diagnosed with ovarian cancer in 2005–09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005–09 was high (54–58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18–23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major defi ciencies in the management of a largely curable disease. Interpretation International comparison of survival trends reveals very wide diff erences that are likely to be attributable to diff erences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems This work was funded by the Canadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer Institute New South Wales, Cancer Research UK (C1336/A16148), US Centers for Disease Control and Prevention (CDC; 12FED03123, ACO12036), Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, and the University of Kentucky (3049024672-12-568)

Background: Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype. Methods: We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center. Results: Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester). Conclusions: Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics. Copyright © 2014 by Lippincott Williams & Wilkins.

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case-control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene-environment interactions. Objectives: The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene-environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods: By September 2012, CLIC included 22 studies (recruitment period: 1962-present) from 12 countries, totaling approximately 31. 000 cases and 50. 000 controls. Of these, 19 case-control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child-parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions: CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene-environment interactions and associations among specific leukemia subtypes in different ethnic groups. © 2013 Elsevier Ltd.

Positive associations have been reported between the measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth - weight-for-gestational-age and proportion of optimal birth weight (POBW) - were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI: 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one-standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI: 0.77, 0.95), respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin-like growth factors. © 2013 UICC.

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but\ud it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility\ud of automatically retrieving information from the medical literature and leveraging this information in GWAS.\ud Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts,\ud and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the\ud phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can\ud subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We\ud initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and\ud subsequently applied it in a two-phase GWAS of oral cancer.\ud Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the\ud oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the\ud ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (perrare-allele\ud log additive p-value [ptrend] = 2.561023\ud ). The combined OR for having one additional rare allele was 0.83 (95% CI:\ud 0.76–0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall\ud UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper\ud aerodigestive tract (UADT), but no additional association signal was found.\ud Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical\ud literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/\ud lld/gwas/service/config).

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p trend < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p trend = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p trend = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p trend < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97). © 2011 Springer Science+Business Media B.V.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case - control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P het) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10 -6) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P het = 6 × 10-4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations.©2011 AACR.

Background Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers.

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3, 800 aerodigestive cancer cases and 5, 200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.