Nathaniel Rothman

Fast track — ArticlesGenetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium

BACKGROUND Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). METHODS We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. FINDINGS The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083). INTERPRETATION Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.

Use and Reliability of Exposure Assessment Methods in Occupational Case–Control Studies in the General Population: Past, Present, and Future

Introduction Retrospective occupational exposure assessment has been challenging in case-control studies in the general population. We aimed to review (i) trends of different assessment methods used in the last 40 years and (ii) evidence of reliability for various assessment methods. Methods Two separate literature reviews were conducted. We first reviewed all general population cancer case-control studies published from 1975 to 2016 to summarize the exposure assessment approach used. For the second review, we systematically reviewed evidence of reliability for all methods observed in the first review. Results Among the 299 studies included in the first review, the most frequently used assessment methods were self-report/assessment (n = 143 studies), case-by-case expert assessment (n = 139), and job-exposure matrices (JEMs; n = 82). Usage trends for these methods remained relatively stable throughout the last four decades. Other approaches, such as the application of algorithms linking questionnaire responses to expert-assigned exposure estimates and modelling of exposure with historical measurement data, appeared in 21 studies that were published after 2000. The second review retrieved 34 comparison studies examining methodological reliability. Overall, we observed slightly higher median kappa agreement between exposure estimates from different expert assessors (~0.6) than between expert estimates and exposure estimates from self-reports (~0.5) or JEMs (~0.4). However, reported reliability measures were highly variable for different methods and agents. Limited evidence also indicates newer methods, such as assessment using algorithms and measurement-calibrated quantitative JEMs, may be as reliable as traditional methods. Conclusion The majority of current research assesses exposures in the population with similar methods as studies did decades ago. Though there is evidence for the development of newer approaches, more concerted effort is needed to better adopt exposure assessment methods with more transparency, reliability, and efficiency.