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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5523. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hill, D. A. Articles by Rothman, N. Search for Related Content PubMed Articles by Hill, D. A. Articles by Rothman, N. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE NHL and genomic variability in RAG1 and BRCA2 Response: In the letter by Scott and colleagues in this issue of Blood, the authors failed to identify an association between RAG1 K820R or BRCA2 N372H variant alleles and risk of non-Hodgkin lymphoma (NHL), while we had observed a relationship in a previous study. Small differences in the ethnicity distribution between the 2 studies probably do not account for the discordant findings, as we did not detect risk estimate heterogeneity according to ethnicity. The 2 studies reported a similar gene variant prevalence among controls, which was also consistent with that seen in other populations.1,2 The similar prevalence suggests another potential explanation for the discrepancy: that small differences in control genotype prevalence, coupled with slightly larger differences in case genotype distributions (as in our studies) can create apparently spurious positive (or null) results. This highlights the possibility that sampling variability may play a major role in seemingly discordant findings. If a slightly different sample of our respective eligible participants had been enrolled, we might have had concordant results. Resolution of this issue in genetic association studies will require very large datasets and thousands of study participants to develop large-scale evidence for genotype-disease associations, as several authors have noted.3–5 Such initiatives are beyond the scope of most single investigations, and have led to the creation of consortia to address these questions, not only through standard meta-analyses, (which can be subject to publication bias), but by pooled analyses of individual-level data from both published and unpublished sources.6 Few results are yet available from these undertakings. The International Lymphoma Epidemiology Consortium (Interlymph), which includes related initiatives focused on other hematopoietic malignancies, is only one of many such consortia,7 and welcomes other investigators to join this collaborative effort. Authorship Correspondence: Deirdre A. Hill, Department of Internal Medicine, University of New Mexico School of Medicine, 1 University of New Mexico, Albuquerque, NM 87131-0001; email: dahill{at}salud.unm.edu. Conflict-of-interest disclosure: The authors declare no competing financial interests. Deirdre A. Hill, Sophia Wang, Patricia Hartge, and Nathaniel Rothman References Wu X, Gu J, Grossman HB, Amos CI, et al. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet 2006; 78:464–479.[CrossRef][Medline] [Order article via Infotrieve] http://snp500cancer.nci.nih.gov accessed 12/12/06. Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet 2003; 361:865–872.[CrossRef][Medline] [Order article via Infotrieve] Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N. Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 2004; 96:434–442.[Abstract/Free Full Text] Ioannidis JP, Trikalinos TA, Khoury MJ. Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases. Am J Epidemiol 2006; 164:609–614.[Abstract/Free Full Text] Ioannidis JP, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nat Genet 2006; 38:3–5.[CrossRef][Medline] [Order article via Infotrieve] Rothman N, Skibola CF, Wang SS, et al. Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. Lancet Oncol 2006; 7:27–38.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: RAG1 and BRCA2 polymorphisms in non-Hodgkin lymphoma Kathryn Scott, Peter J. Adamson, Sharon L. Barrans, Lisa J. Worrillow, Eleanor V. Willett, and James M. Allan Blood 2007 109: 5522-5523. [Full Text] [PDF] Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes Deirdre A. Hill, Sophia S. Wang, James R. Cerhan, Scott Davis, Wendy Cozen, Richard K. Severson, Patricia Hartge, Sholom Wacholder, Meredith Yeager, Stephen J. Chanock, and Nathaniel Rothman Blood 2006 108: 3161-3167. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hill, D. A. Articles by Rothman, N. Search for Related Content PubMed Articles by Hill, D. A. Articles by Rothman, N. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?

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