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Standardization within the consortium Cancer consortia. Paolo Boffetta IARC. IARC-coordinated cancer consortia. INTERLYMPH >20 case-control studies of lymphoma ILCCO >40 case-control and cohort studies of lung cancer INHANCE ~20 case-control studies of head and neck cancer.
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Standardization within the consortiumCancer consortia Paolo Boffetta IARC
IARC-coordinated cancer consortia • INTERLYMPH • >20 case-control studies of lymphoma • ILCCO • >40 case-control and cohort studies of lung cancer • INHANCE • ~20 case-control studies of head and neck cancer
Characteristics of IARC cancer consortia • Emphasis on pooling of independently collected results • Coordinated generation of new data • Projects proposed and managed by working groups • Light central coordination • Expansion to low- and medium-resource countries
Data flow • No central facility for data management and analysis • A common database has accumulated starting with the initial pooled analyses and including more and more data • Contacts between people involved in subsequent analyses
Phenotype standardizationExample of InterLymph • Pathological and genetic heterogeneity • Background • reviews conducted within studies • need for network-wide review? • Pathology working group • epidemiology-oriented classification • hierarchical • limited review (5 • % of 10,000 cases)
Data flow - Steps • Collection of study protocols, questionnaires and other forms • posted on website • Data provided by PI • specific vs. free data format • Checking and cleaning of data • Pooled analysis • performed by working group • detailed preliminary results circulated among PI • test of heterogeneity among studies, sensitivity analyses
Pooled AnalysesHead & Neck Cancer SNP • 11 SNPs in metabolic genes, 7 in DNA repair genes • 10 case-control studies from the US and Europe • Request % undetermined and % concordance for quality controls from each study • Test for heterogeneity by: • Laboratory sources: genotyping method, source of DNA • Study characteristics: hospital vs. population-based, study period, sample size • Other: ethnicity, age, smoking, alcohol drinking, subsite • Standardization – adjust for variables that contribute to heterogeneity, present overall OR and stratified OR
Novel analysesImmunological SNP in InterLymph • Selection of a list of relevant SNP • 12 SNP related to immunological response • Analysis of DNA samples in five laboratories • four used Taqman • one used Pyrosequencing or allele-specific PCR • Quality control • 102 DNA samples from ethnically diverse individuals that previously had been sequenced and genotyped (SNP500Cancer project) • assays not in Hardy Weinberg Equilibrium (HWE) among controls were re-checked Rothman et al., submitted