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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5522-5523. 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 Scott, K. Articles by Allan, J. M. Search for Related Content PubMed Articles by Scott, K. Articles by Allan, J. M. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE RAG1 and BRCA2 polymorphisms in non-Hodgkin lymphoma To the editor: A recent Blood paper by Hill et al1 suggested a link between the risk of developing non-Hodgkin lymphoma (NHL) and polymorphic variations in several genes involved in DNA strand break induction and DNA repair pathways. We examined 2 of these polymorphisms where Hill et al reported statistically significant associations, in the Recombination-activating 1 (RAG1) gene (K820R; odds ratio [OR] = 2.7 [AA vs GG], 95% confidence interval [CI], 1.4-5.0) and the Breast cancer 2 (BRCA2) gene (N372H; OR = 1.5 [AA vs CC], 95% CI, 1.0-2.1), in a United Kingdom case-control study of lymphoma. Local ethical approval was obtained for this research. Informed consent was obtained in accordance with the Declaration of Helsinki. A total of 741 white patients with NHL and 806 white control participants randomly selected from population registers were recruited as part of a lymphoma case-control study conducted in parts of north and southwest England.2 Our study participants consented to give a blood sample, and represented 67% of patients with incident NHL aged 16 to 69 years in the study area and 66% of the control participants who were contacted successfully. We genotyped the participants' DNA while blinded to case-control status using TaqMan SNP genotyping assays (Applied Biosystems, Warrington, United Kingdom) and ABI PRISM 7000 software (Applied Biosystems). To assess the reliability of the Taqman assays, 20 samples were randomly selected for direct DNA sequencing: concordance with TaqMan was 100% for both polymorphisms. Among our control population, RAG1 K820R and BRCA2 N372H were in Hardy-Weinberg equilibrium, and the distributions of variants were consistent with those reported by Hill et al and the cancer genome anatomy project SNP500 cancer database.3 Unmatched statistical analyses to estimate ORs and 95% CIs were conducted using unconditional logistic regression adjusting for age and sex,4 and the likelihood ratio test was used to test for interactions. We observed a modest but nonsignificant decrease in risk of NHL with BRCA2 N372H AC and CC variants compared with the AA variant, and no evidence of any association between NHL and the RAG1 K820R polymorphism (Table 1). Risks for B-cell lymphoma, and the 2 major diagnostic subgroups of diffuse large B-cell lymphoma and follicular lymphoma (data not shown), were similar to those for total NHL for both variants, while risk estimates were elevated for T-cell lymphoma, but were not significant (Table 1). Risks were generally similar among men and women, and varied little by age (data not shown). However, for T-cell lymphoma, men who carried at least 1 copy of the BRCA2 N372H C allele had a significantly increased risk (OR = 2.30, 95% CI, 1.08-4.87 based on 23 patients and 194 control participants with the C allele compared with 11 patients and 208 control participants), while women were at decreased risk (OR = 0.43, 95% CI, 0.17-1.06 based on 7 patients and 176 control participants with the C allele compared with 17 patients and 179 control participants) (test for interaction: 2 = 8.42, P = .004). View this table: [in this window] [in a new window]   Table 1. Number of patients and control participants, adjusted ORs, and 95% CIs for BRCA2 N372H and RAG1 K820R by immunophenotype   Our data suggest that there is little association between NHL and either of these 2 polymorphisms. However, we cannot exclude the possibility of an association, and further investigation is required using larger datasets to elucidate the role of these polymorphisms in determining the risk of developing NHL. Authorship Correspondence: Kathryn Scott, Department of Biology, University of York, York. United Kingdom YO10 5YW; e-mail: KS27{at}YORK.AC.UK Conflict-of-interest disclosure: The authors declare no competing financial interests. Kathryn Scott, Peter J. Adamson, Sharon L. Barrans, Lisa J. Worrillow, Eleanor V. Willett, and James M. Allan References Hill DA, Wang SS, Cerhan JR, et al. Risk of Non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes. Blood 2006; 108:3161–3167.[Abstract/Free Full Text] Willett EV, Smith AG, Dovey GJ, et al. Tobacco and alcohol consumption and the risk of non-Hodgkin lymphoma. Cancer Causes Control 2004; 15:771–780.[CrossRef][Medline] [Order article via Infotrieve] National Cancer Institute. Cancer Genome Anatomy Project SNP500 Cancer Database. Available at: http://snp500cancer.nci.nih.gov. Accessed June 2006. Breslow NE and Day NE. Classical methods of analysis of matched data. Statistical methods in cancer research: the analysis of case-control studies volume 1. 1980;Lyon International Agency for Research in Cancer162–189. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: NHL and genomic variability in RAG1 and BRCA2 Deirdre A. Hill, Sophia Wang, Patricia Hartge, and Nathaniel Rothman Blood 2007 109: 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 Scott, K. Articles by Allan, J. M. Search for Related Content PubMed Articles by Scott, K. Articles by Allan, J. M. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?

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