期刊
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
卷 22, 期 2, 页码 295-307出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-12-1122
关键词
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资金
- NIH [K07-CA-140360, R25-CA-87949]
- NIH (NCI) [U01-AI-035040]
- NIH (UCLA CFAR) [P30-AI-028697, R01-CA-057152, R01-CA-121195, R01-CA-168482]
- NIH (UCLA Older Americans Independence Center) [P30-AG-02874]
- National Institute of Allergy and Infectious Diseases
- National Cancer Institute [UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041]
- James B. Pendleton Charitable Trust
- McCarthy Family Foundation
Background: CXCL13 and CXCR5 are a chemokine and receptor pair whose interaction is critical for naive B-cell trafficking and activation within germinal centers. We sought to determine whether CXCL13 levels are elevated before HIV-associated non-Hodgkin B-cell lymphoma (AIDS-NHL), and whether polymorphisms in CXCL13 or CXCR5 are associated with AIDS-NHL risk and CXCL13 levels in a large cohort of HIV-infected men. Methods: CXCL13 levels were measured in sera from 179 AIDS-NHL cases and 179 controls at three time-points. TagSNPs in CXCL13 (n = 16) and CXCR5 (n = 11) were genotyped in 183 AIDS-NHL cases and 533 controls. OR and 95% confidence intervals (CI) for the associations between one unit increase in log CXCL13 levels and AIDS-NHL, as well as tagSNP genotypes and AIDS-NHL, were computed using logistic regression. Mixed linear regression was used to estimate mean ratios (MR) for the association between tagSNPs and CXCL13 levels. Results: CXCL13 levels were elevated for more than 3 years (OR = 3.24; 95% CI = 1.90-5.54), 1 to 3 years (OR = 3.39; 95% CI = 1.94-5.94), and 0 to 1 year (OR = 3.94; 95% CI = 1.98-7.81) before an AIDS-NHL diagnosis. The minor allele of CXCL13 rs355689 was associated with reduced AIDS-NHL risk (ORTCvsTT = 0.65; 95% CI = 0.45-0.96) and reduced CXCL13 levels (MRCCvsTT = 0.82; 95% CI = 0.68-0.99). The minor allele of CXCR5 rs630923 was associated with increased CXCL13 levels (MRAAvsTT = 2.40; 95% CI = 1.43-4.50). Conclusions: CXCL13 levels were elevated preceding an AIDS-NHL diagnosis, genetic variation in CXCL13 may contribute to AIDS-NHL risk, and CXCL13 levels may be associated with genetic variation in CXCL13 and CXCR5. Impact: CXCL13 may serve as a biomarker for early AIDS-NHL detection. Cancer Epidemiol Biomarkers Prev; 22(2); 295-307. (c) 2012 AACR.
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