Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut

Kyoung Mu Lee, Dalsu Baris, Yawei Zhang, H. Dean Hosgood, Idan Menashe, Meredith Yeager, Shelia Hoar Zahm, Sophia S. Wang, Mark P. Purdue, Stephen Chanock, Tongzhang Zheng, Nathaniel Rothman, Qing Lan

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Abstract

In light of the relationship between immune system dysregulation and multiple myeloma (MM) risk, we investigated whether genetic variation in 92 immune function genes among 77 gene regions are associated with MM susceptibility in a population-based case-control study (108 cases and 482 controls) conducted among Caucasian women in Connecticut. Tagging single-nucleotide polymorphisms (SNPs; N = 870) were selected using a pairwise linkage-disequilibrium based algorithm. Odds ratios (ORs) and 95% confidence intervals (CIs) for SNP genotypes were estimated using unconditional logistic regression. Tests of association for gene regions were conducted using the minP test. We applied the false discovery rate (FDR) method to the minP test results as a means of controlling for multiple comparisons. The CD4 gene region located on 12p13-q13 (minP 5 0.0009), had an FDR value <0.1. In this region, a total of six tag SNPs in two genes (CD4 and LAG3) were significantly associated with MM risk (Ptrend<0.05), with the strongest association observed for the CD4 variant rs11064392 (ORAG/GG = 2.53, 95% CI = 1.59-4.02). Our findings suggest that genetic variation in CD4 may influence susceptibility to MM. Additional studies are needed to replicate these findings and, more generally, to explore the manner in which genes and receptors may influence the pathogenesis of this poorly understood malignancy.

Original languageEnglish (US)
Pages (from-to)560-563
Number of pages4
JournalAmerican Journal of Hematology
Volume85
Issue number8
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Lee, K. M., Baris, D., Zhang, Y., Hosgood, H. D., Menashe, I., Yeager, M., Zahm, S. H., Wang, S. S., Purdue, M. P., Chanock, S., Zheng, T., Rothman, N., & Lan, Q. (2010). Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut. American Journal of Hematology, 85(8), 560-563. https://doi.org/10.1002/ajh.21760