Abstract A78: Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut

Abstract

Abstract A78 Background Increased risk of multiple myeloma has been observed among those who have a family history, suggesting a genetic component in multiple myeloma development. Also, a number of studies have shown that changes in immuoregulatory role of T cells may contribute to the development of multiple myeloma. Objective In light of the relationship between immune system dysregulation and multiple myeloma risk, we investigated whether genetic variation in 153 immune function genes are associated with multiple myeloma susceptibility in a population-based case-control study conducted among White Connecticut women. Methods Tagging single-nucleotide polymorphisms (SNPs; N=876) 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. Haplotype analyses among subjects were performed using the haplo.stat statistical package in the R program. Haplotype frequencies were estimated from genotype data using the expectation-maximization algorithm while at the same time excluding those with frequencies less than 1%, and were evaluated by the global score test. Results Six out of 75 gene regions were significantly (P<0.05) associated with multiple myeloma using the MinP test. However, only the PTMS-LAG3-CD4-GPR162-LEPREL gene region remained noteworthy after adjustment for multiple tests using the FDR method (minP=0.0018; noteworthy at a level of FDR control of 0.14). In this region, a total of six SNPs in two genes (CD4 and LAG3) were significantly associated with risk (Ptrend<0.05), with the strongest association observed for rs11064392 (ORAG/GG=2.53, 95% CI=1.59-4.02; Ptrend=0.0001). Haplotype analyses also supported an association with rs11064392. Conclusion Our findings suggest that genetic variation in CD4 may influence susceptibility to multiple myeloma. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A78.