1. Standardization within the consortium Cancer consortia Paolo Boffetta IARC

2. 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

3. 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

4. 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

5. Phenotype standardization Example 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)

6. 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

7. Pooled Analyses Head & 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

8. Novel analyses Immunological 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