ALBERT

Description: Hodgkin lymphoma (HL) is derived from germinal center B-lymphocytes, has a peak incidence in adolescents and young adults (AYA) in developed countries and results in substantial treatment-related late effects. We previously identified a SNP (rs1860661G) in the TCF3 gene, inversely associated with HL risk, that is also mutated in tumor cells. The protein encoded by TCF3 is responsible for maintaining the B-cell program, which is downregulated in HRS cells; therefore higher expression levels may be protective.1 DNA methylation is associated with repression of gene expression and may thereby play a role in HL pathogenesis. We extracted DNA from blood samples obtained from HL survivors and their unaffected monozygotic MZ twins (4 female and 5 male twin pairs discordant for AYA HL). Average age at blood draw was 62 years, and average time since diagnosis of the case was 34 years. We also extracted DNA from blood samples from 25 unaffected MZ twin pairs as control pairs. DNAs were bisulfite converted and DNA methylation quantified using the Illumina Infinium HumanMethylation27 BeadChip array, which scores methylation levels as β values. We compared average DNA methylation β value differences at the TCF3 locus cg16524139 (near rs1860661) in HL survivors and their unaffected co-twins using a paired t-test. We also examined the TCF3 germline genotype by DNA methylation level rank in HL-discordant pairs. We also computed DNA methylation age, a global measure of physiological aging, using a validated algorithm2 and compared the result in the HL survivor to that of each corresponding unaffected co-twin using a paired t-test. We found a small but significantly higher DNA methylation level at the TCF3 locus in HL survivors compared to their unaffected co-twins (p=0.05), but no difference between the members of healthy MZ twin pairs (p=0.81). The protective allele (G) was more prevalent in the 6 pairs with higher DNA methylation level in HL survivors (33%), compared to the 3 pairs with higher levels in unaffected co-twins (17%). This pattern would be expected if methylation at the cg16524139 were to diminish TCF3 expression related to a protective rs1860661G variant. HL survivors had an average DNA methylation age of 64.1 years compared to 61.3 years in their unaffected MZ co-twins (p=0.04). Differential DNA methylation in HL survivors and their unaffected twins suggests a role for DNA methylation in HL, possibly as a result of treatment or disease. 1. Cozen W, Timofeeva MN, Li D, Diepstra A, Hazelett D, Delahaye-Sourdeix M, et al.: A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus. Nat Comm 25:3856. doi: 10.1038/ ncomms 4856, 2014 2. Horvath S: DNA methylation age of human tissues and cell types. Genome Biol, 14:R115 doi:10.1186/gb-2013-14-10-r115, 2013. Disclosures No relevant conflicts of interest to declare.

Description: Multiple myeloma (MM) is 2-3 times more common among African-Americans compared to non-Hispanic whites. The 2-3-fold increased risk among family members of cases suggests a genetic contribution to risk. Genome-wide association studies (GWAS) in populations of European ancestry have identified seven novel risk loci at 2p23.3 (rs6746082), 3q26.2 (rs10936599), 3p22.1 (rs1052501), 6p21.32 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077) and 22q13.1 (rs877529) (Broderick, et al. Nat Genet, 2011, Chubb, et al. Nat Genet, 2013), three of which were replicated in another European series (Martino et al., Br J Haematol, 2012). Here we examined the index signals and conducted fine-mapping for each locus in a case-control study of 1,049 multiple myeloma cases and 7,084 controls of African ancestry to identify better markers of risk and novel independent loci in seven previously reported regions in this high risk population. Incident cases were recruited from 10 clinical centers and SEER cancer registries from 2011 to 2013 and genotyped using the Illumina HumanCore GWAS array. Control data were obtained from previous genome-wide studies of breast and prostate cancer, genotyped using the Illumina 1M-Duo in 4425 male controls from the African Ancestry Prostate Cancer Consortium (consisting of 14 independent studies) and 2632 female controls from a breast cancer GWAS of African-American women (consisting of 9 independent studies). Imputation to 1000 Genomes (March 2012 release) was conducted for regions around six of the previously identified single nucleotide polymorphisms [SNPs] (the HLA region harboring rs2285803 is still being imputed, results will be presented). A case-control analysis of SNPs/indels 〉1% frequency within 250 kb of each index variant was conducted using unconditional multivariable logistic regression adjusting for age, sex and five leading principal components. Region-specific alpha levels were determined through permutation tests. The minimum alpha level across the six regions was α=0.002. All previously reported risk variants were common in African-Americans (minor allele frequency [MAF] 〉0.05). For five of the six SNPs, we had ≥94% power to detect the same effect observed in non-Hispanic whites, and 64% power for the less common variant rs10936599 (MAF=0.07). We observed directionally consistent effects (odds ratio [OR]〉1) for the six risk variants tested, with three replicating at p≤0.05 (7p15.3, p=1.4x10-7; 17p11.2, p=0.05; 22q13.1, p=0.02). For three of the six regions, we observed better markers of risk in African-Americans that were correlated with the index SNP in Europeans (7p15.3, rs56333627, p=1.5x10-5, r2=0.89; 17p11.2, rs34562254, p=2.9x10-3, r2=0.90; 22q13.1, rs2092410, p=1.1x10-4 r2=.71). The missense variant identified in the 17p11.2 region (rs34562254, Pro251Leu) is located in TNFRSF13B, which encodes the protein TACI, a B cell surface receptor which plays a role in B cell maturation, apoptosis and antibody production by inducing activation of transcription factors including NFAT and NFκβ. In addition, there is evidence suggesting that TACI is involved in MM pathogenesis. Our results demonstrate that many of the risk loci for MM found in European ancestry populations are also risk loci in men and women of African ancestry and that by fine-mapping, we are able to identify variants that better capture risk in populations of African ancestry. Disclosures Terebelo: Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

Description: Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 × 10−10), rs204999 (P = 1.44 × 10−9), and rs2858870 (P = 1.69 × 10−8). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 × 10−10). rs204999 and rs2858870 were weakly correlated (r2 = 0.257), and the remaining pairs of SNPs were not correlated (r2 〈 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 × 10−6; GAATC, OR = 0.4, P = 1.16 × 10−4). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology.

Description: Background: Persons of African ancestry (AA) have a 2-3-fold higher risk of multiple myeloma (MM) than persons of European ancestry (EA). Like other B-cell malignancies, genome-wide association scans (GWAS) have identified MM risk variants in the HLA region in persons of EA. We conducted a case-control analysis with data from the National Marrow Donor Program (NMDP)1comprising MM patients typed for bone marrow transplant to donor controls matched by race-ethnicity, and found associations between specific HLA alleles/haplotypes and MM risk that varied by race and ethnicity. To confirm our results and identify additional novel signals, we have now investigated associations between HLA alleles and haplotypes and MM risk in the African American Multiple Myeloma Study (AAMMS) Cohort. Methods: The source of subjects was the AAMMS, in which AA MM patients were identified from 10 cancer centers and 4 Surveillance, Epidemiology and End-Results (SEER) Program cancer registries in order to identify genetic risk factors for MM among AAs. A GWAS was conducted using the Illumina Human Core BeadChip array on DNA samples from 1,305 AA MM patients in the AAMMS comparing results to those from 7,078 AA controls with GWAS data generated from the Illumina 1MDuo2. The major histocompatibility complex (MHC) region single nucleotide polymorphisms (SNPs) were imputed to classical HLA variants using HIBAG. Unconditional logistic regression was used to estimate HLA associations, adjusting for sex, age and the first 2 principal components. P-values were adjusted for false discovery rate (FDR) for each locus group. Results: We did not identify any single HLA alleles associated with MM risk among AAs. However, several B*07:02-containing haplotypes were associated with MM risk (odds ratios [OR] ranging from 2.38 to 2.64 and FDR P-values ranging from 1.43 x 10-6 to 3.57 x 10-8). We found associations between MM risk and genotypes containing DRB3*02:02, including DRB3*02:02~DRB1*11:01+ DRB3*02:02~DRB1*11:01 (OR=1.93, PFDR= 9.36 x 10-5) similar to those observed in the NMDP study1. Novel findings included associations between MM risk and HLA Class I haplotypes B*53:01+ B*57:01 (OR=1.94, PFDR= 0.003) and C04:01~B*53:01+C*06:02~B*57:01 (OR=1.96, PFDR= 0.0050). Results from an ongoing meta-analysis between the two data sets (one based on an imputed GWAS and one based on NMDP HLA typing) will be presented. Conclusions: This study is the second to examine HLA alleles and risk of MM among AA's and is by far the largest. We confirmed a previously observed association between an HLA Class II DRB3 variant and MM risk and confirmed an association with B*07 haplotypes previously observed among EAs1. We also identified novel associations between other HLA Class I haplotypes and MM risk in AA's. Because HLA is highly polymorphic, many HLA alleles are rare variants for which genetic associations are difficult to detect without very large sample sizes. Further investigation with large sample sizes will be necessary to refine these associations in order to better identify the underlying causal alleles and determine the functional significance of these HLA associations. 1Beksac M, Gragert L, Fingerson S, et al.: HLA polymorphism and risk of multiple myeloma.Leukemia. 2016 Jul 27. doi: 10.1038/leu.2016.199. 2Rand KA, Song C, Hwang AE, et al. Genetic susceptibility markers of multiple myeloma in African-Americans. Abstract # 2030, 56th Annual American Society of Hematology Meeting, San Francisco, California, 2014. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Nooka:Spectrum, Novartis, Onyx pharmaceuticals: Consultancy. Zonder:Pharmacyclics: Other: DSMC membership; Prothena: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Lonial:BMS: Consultancy; Novartis: Consultancy; Millenium: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Merck: Consultancy; Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Onyx: Consultancy; Janssen: Consultancy; Onyx: Consultancy.

Description: Introduction African-American ethnicity, male sex, older age and obesity are accepted risk factors for multiple myeloma (MM). Obesity early in life is a risk factor for many cancers, including MM; most studies have focused on populations of European origin. African-Americans have a higher prevalence of obesity than other populations, and may have a distinct genetic contribution to this condition. We established a multi-center collaborative study to investigate possible explanations for the excess risk of MM among African-Americans. The aim of the present case-case analysis was to determine whether body mass index (BMI) was associated with risk factors and clinical characteristics at presentation in African-American MM patients. Methods Patients diagnosed with active MM since January 1, 2009 were recruited from nine outpatient centers and three Surveillance, Epidemiology, End-Results Program (SEER) population-based cancer registries. Information on weight and height at 20 years of age and at 5 years prior to diagnosis was obtained from questionnaires. Clinical information collected included age at diagnosis, stage, percent plasmacytosis on bone marrow biopsy, β2 microglobulin level, Ig serotype, light vs. heavy chain disease, and presence of lytic bone lesions. BMI (ht/wt2) was categorized into 3 levels (normal 30) according to World Health Organization standard. The Pearson chi-square test was used to test the association between BMI category, and risk factors and clinical characteristics. Mean ages at diagnosis across BMI categories were compared using linear regression and a t-test for trend calculated. Results To date, 1,044 African-American MM patients have been enrolled and of those, 1,014 provided a DNA sample. At present, 970 patients have completed a questionnaire, clinical records have been abstracted for 823 patients, and 509 patients have some information on gender, age at diagnosis, weight, height and clinical characteristics.The mean age at diagnosis was 59. Increasing BMI at age 20 was associated with younger age at diagnosis (p= 0.0004), whereas BMI at 5 years prior to diagnosis was not associated with age at diagnosis (p=0.9477). Among men, mean age at diagnosis decreased with increasing BMI at age 20 (p= 0.0125) (Table 1a) and at 5 years prior to diagnosis (p=0.0252) (Table 1b). Among women, the trend was signficant at age 20 (p=0.0018) (Table 1a) but not at 5 years prior to diagnosis (p= 0.7094) (Table 1b). Increasing BMI was not significantly associated with any other clinical characteristics. Conclusion/Discussion In a large collection of African-American MM patients, we observed a strong association between increasing BMI at age 20 and younger age at diagnosis. A similar trend was observed in men only at 5 years prior to diagnosis, consistent with previous reports. Obesity is one of the few known potentially modifiable risk factors for MM. Younger age at diagnosis reflects an earlier accumulation of either or both genetic and environmental risk factors. Obesity at an early age may influence MM risk through shared biological pathways such as interleukin-6 and insulin-like growth factor, by contributing to chronic B-cell activation, thereby increasing susceptibilty for MM later in life. The significance of the gender difference for the association closer to diagnosis is unclear and requires additional study. Disclosures: Terebelo: Amgen: Honoraria; Millennium: Honoraria. Mehta:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Zonder:Skyline: Consultancy. Orlowski:Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millennium: The Takeda Oncology Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Resverlogix: Research Funding; Array Biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Membership on an entity’s Board of Directors or advisory committees. Lonial:Celgene Corporation: Consultancy; Millennium: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.

Description: Both Hodgkin lymphoma (HL) and asthma are associated with relative isolation from early childhood infectious exposures (hygiene hypothesis) and a T-helper-2 (Th2)-skewed immune response. To test the hypothesis that there is some component of shared genetic etiology between HL and asthma, we examined the genetic overlap in data from genome-wide association study (GWAS) meta-analyses of the two diseases conducted in populations of European ancestry. The HL GWAS meta-analysis consisted of 1,816 HL cases and 7,877 controls, and the asthma GWAS meta-analysis consisted of 2,088 asthma cases and 2,743 controls. The combined HL-asthma GWAS data resulted in 904,634 common single nucleotide polymorphisms (SNPs) genotyped with both arrays. We observed a total of 9 common SNPs associated with both HL and asthma at p

Description: Background Recent genome wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified several associations at both HLA and non-HLA loci. However, much of HL heritability remains unexplained. Methods To identify novel risk loci, we performed a meta-analysis of 3 HL GWAS including a total of 1,810 cases and 7,879 controls. Results were replicated in an independent set of 1,163 cases and 2,580 controls, for a total of 3,097 and 11,097 cases and controls combined, respectively. participants in discovery and replication stages were of European descent. quality control and imputation we conducted a meta-analysis addressing 1,004,829 variants (λ= 1.10, λ1000= 1.03). Associations between SNP genotypes and HL risk were evaluated under a log-additive model of inheritance adjusting for sex, study center and significant principal components to control for population stratification. We performed an analysis with all HL cases and then conducted stratified analyses by histological subtype (classical, nodular sclerosis and mixed cellularity), age at diagnosis (nodular sclerosis among those diagnosed at 15- 35 years in all studies, and those diagnosed at 35 and older years in the European Study only) and EBV tumor status (negative and positive). We then used a bioinformatic approach (FunciSNP) to identify potential functional variants associated with HD risk correlated with risk loci of interest. We extracted publically available ENCODE data on biofeatures to identify potential functional motifs associated with the index SNP or correlated SNPs. Finally, we measured expression levels of the two alternative mRNA transcripts in lymphoblastoid cell lines (LCLs) from 49 post-therapy HL patients and 25 unaffected controls. RT-PCR was carried out in triplicate. Relative expression levels were calculated relative to TBP as housekeeping gene. Linear models were used to assess correlation between genotype and TCF3expression levels. Results The meta-analysis identified a novel susceptibility variant at chromosome 19p13.3 (rs1860661) associated with HL risk (Odds Ratio [OR]= 0.78, P=2.0*10-8, I2=0%). variant is located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment. was also significantly associated with HL (OR= 0.85, P=0.002) in the replication series of 1,281 cases and 3,218 controls. the combined analysis consisting of the discovery and replication sets, rs1860661was strongly associated with HL (OR=0.81,=3.5*10-10), with no evidence of heterogeneity between contributing studies (Phom=0.41, I2=0%). The number of G alleles defined by rs1860661 was significantly associated with a reduced risk of each HL subtype except EBV positive HL. rs1860661 and two correlated SNPs, rs10413888 (r2=0.90) and rs8103453 (r2=0.89) identified by FunciSNP analysis map in or near marks of open chromatin and in DNAse hypersensitivity sites in TCF3 in CD20+ B cell lines., the protective minor alleles of these SNPs as defined by the G-G-G haplotype map to the binding sites for ZBTB7a (rs10413888 and rs1860661) and (rs8103453) transcription factors, likely improving the binding efficiency to the sites which may result in increased transcription rates of TCF3. TCF3 is encoded by two alternative transcripts (E12 and E47). Higher expression levels of TCF3-E47, whose transcription start site is located close to rs1860661, was associated with the rs1860661-G allele in controls (P=0.02), but not in HL patients (P=0.22). Conclusion/Discussion TCF3 is essential for the commitment of lymphoid progenitors to both B-cell and T-cell lineage development. A molecular and phenotypic hallmark of classical HL is the loss of the B-cell phenotype in HRS cells, including lack of demonstrable B-cell receptor and most B-cell specific markers such as CD19 or CD20. HRS cells have a low level of TCF3, particularly homodimers of the isoform E47, due to expression of the ABF-1 and ID2 inhibitors that bind to TCF3. Thus, higher TCF3 levels in HRS precursor cells may lead to enhanced retention of the B cell phenotype, thereby conferring a protective effect. These data suggest a link between the 19p13.3 locus including TCF3 and HL risk, indicating that TCF3 could be relevant to HL etiology and pathogenesis. Disclosures: Link: Genentech: Consultancy; Millenium: Consultancy; Pharmacyclics: Consultancy; Spectrum: Consultancy.

Description: Introduction The 2-3 fold excess risk of multiple myeloma (MM) among family members of cases suggests a heritable contribution to risk. Recently, a genome-wide association study (GWAS) identified two genome-wide significant and one promising novel loci associated with multiple myeloma risk. To confirm these associations and identify additional novel risk loci, we performed a four-center, genome-wide association meta-analysis. Methods A fixed effects model was used for the meta-analysis which included a total of 1248 cases and 1485 controls, all of European descent, genotyped and analyzed at four separate centers with samples contributed by 10 studies. After quality control and imputation using the 1000 Genomes Project, the analysis included ∼9.5 million variants (λ=1.024). Associations between (single nucleotide polymorphisms) SNP genotypes and MM risk were evaluated under a log-additive model of inheritance, with each study adjusting for age, sex, and up to 10 principal components to control for population stratification. Promising results were replicated in an independent set of 1587 cases and 1770 controls using TaqMan, for a total of 2835 and 3255 cases and controls, respectively, in a combined meta-analysis. Results The discovery meta-analysis did not reveal any genome-wide significant associations (defined as p

Description: Introduction The etiology of multiple myeloma remains unknown, but some heritable contribution is suspected. Very few genetic risk markers have been reported in more than one study population. A nested analysis (72 cases, 144 controls) in the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts suggested a role in multiple myeloma susceptibility for single nucleotide polymorphisms (SNP) in the genes for the insulin receptor substrate type 1 (IRS1; rs17208470, rs1801278) and the interleukin (IL)-6 receptor (IL6R; rs6684439, rs7529229, rs2228145). The NHS and HPFS cohort members are predominantly of European origin; the present analysis further explored the IRS1 and IL6R loci in persons of European descent and in African Americans in a large pooled population comprised of five U.S. population-based studies. Methods We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) assuming a log-additive inheritance model and adjusting for age, sex, and study site. We performed all analyses separately in 824 participants of European origin (259 cases, 565 controls) and 298 African Americans (114 cases, 186 controls). We also calculated a risk allele score by summing all variant alleles across the five SNPs in the ∼95% of participants with no missing genotype data, and we used additional logistic regression models to estimate a race-specific multivariable OR and 95% CI for multiple myeloma risk per variant allele carried. All statistical tests were two-tailed and assumed an α-error of 0.05. Results In persons of European descent, at the locus rs17208470 (IRS1) we observed a statistically significant 42% increase in multiple myeloma risk per copy of the variant allele (OR, 95% CI: 1.42, 1.02-1.98; p=0.037). In IL6R, we observed a statistically significant association with multiple myeloma at rs6684439 (OR, 95% CI: 1.27, 1.01-1.58; p=0.037) and marginally significant associations with multiple myeloma at two loci: rs7529229 (1.24, 0.99-1.55, p=0.057) and rs2228145 (1.24, 0.99-1.55, p=0.056). The risk allele score analysis (240 cases, 532 controls of European origin with no missing genotype data) showed that the risk of multiple myeloma increased significantly by 11% per variant allele carried (OR, 95% CI per risk allele: 1.11, 1.03-1.19; p=0.008). In African Americans, two loci in IL6R, rs6684439 and rs7529229, showed suggestive non-significant associations with multiple myeloma risk (rs6684439, OR, 95% CI, p-value per copy of the minor allele: 1.37, 0.94-2.00, p=0.11; rs7529229: 1.39, 0.95-2.04, p=0.089). Neither SNP in IRS1 was associated with multiple myeloma in this group. The risk allele score analysis in African Americans (109 cases, 176 controls) suggested a 17% increase in multiple myeloma risk per variant allele carried (1.17, 0.99-1.38; p=0.067). Discussion Based on a priori hypotheses, we examined the association of five previously reported SNPs in IRS1 and IL6R with multiple myeloma in a larger series of persons of European descent than previously published, and for the first time, in African Americans. Both genes belong to biologic signaling pathways with important roles in multiple myeloma pathogenesis. In participants of European origin, SNPs in IRS1 and IL6R were at least marginally associated with multiple myeloma, and the risk of multiple myeloma increased significantly per risk allele carried. We observed slightly stronger ORs for the IL6R SNPs in African Americans, but no associations were statistically significant in that group, probably due to a lack of statistical power because of small numbers for this subgroup and/or because the true causal SNPs in these genes have differential linkage disequilibrium across racial groups. The nominally significant and suggestive associations that we observed are plausible and should be further evaluated in other large multi-ethnic studies of multiple myeloma susceptibility. Disclosures: Anderson: celgene: Consultancy; onyx: Consultancy; gilead: Consultancy; sanofi aventis: Consultancy; oncopep: Equity Ownership; acetylon: Equity Ownership.