Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut.
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 = 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 (P(trend)<0.05), with the strongest association observed for the CD4 variant rs11064392 (OR(AG/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.
Lee
Kyoung-Mu
KM
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. kmlee92@snu.ac.kr
Baris
Dalsu
D
Zhang
Yawei
Y
Hosgood
H Dean
HD
Menashe
Idan
I
Yeager
Meredith
M
Zahm
Shelia Hoar
SH
Wang
Sophia S
SS
Purdue
Mark P
MP
Chanock
Stephen
S
Zheng
Tongzhang
T
Rothman
Nathaniel
N
Lan
Qing
Q
D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D015704:CD4 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003237:Connecticut / Q000453:epidemiology; D005260:Female; D005802:Genes, MHC Class II; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D015704:CD4 Antigens; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human