Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients.

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07-5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45-2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.

Alcohol, tobacco, and marijuana consumption is associated with increased odds of same-day substance co- and tri-use.

BACKGROUND: Little is known about event-level patterns of marijuana co- or tri-use with alcohol and tobacco. Thus, the study goal was to examine patterns of same-day alcohol, cigarette, and marijuana co- and tri-use at the individual level in non-treatment-seeking alcohol users. METHODS: Participants (N = 551) completed an in-person interview for alcohol, cigarette, and marijuana use over the previous 30 days, and the event-level substance use patterns of n = 179 participants who reported using each of these substances at least once per month were analyzed. RESULTS: The use of alcohol, marijuana, or cigarettes independently increased the probability of subsequent, simultaneous co-use of one of the two remaining substances. The co-use of alcohol with cigarettes and marijuana with cigarettes produced generally additive effects on the odds of same day tri-use of marijuana and alcohol, respectively. Conversely, the co-use of alcohol and marijuana produced sub-additive effects on likelihood of cigarette use. Sex moderated several of the observed patterns of co- and tri-use: the relationship between alcohol or cigarette use predicting marijuana co-use was stronger in men, whereas the observed additive relationships between drug co-use leading to tri-use was stronger in women. CONCLUSIONS: The presented results may aid in the understanding of how simultaneous co-use of marijuana with alcohol and/or tobacco relates to the etiology, maintenance, and treatment of comorbid and trimorbid substance use disorder. Replication and extension of the results in treatment seeking populations using more fine-grained analysis approaches, e.g. ecological momentary assessment, is needed.

The CRHR1 gene, trauma exposure, and alcoholism risk: a test of G × E effects.

The corticotropin-releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. On the basis of the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and single-nucleotide polymorphisms (SNPs) in predicting the risk for alcoholism. Phenotypic data on 2533 non-related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment genome-wide association study. Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes/SNPs and adulthood traumatic stress exposure in predicting alcoholism risk. Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (P = 0.029) and two haplotypes in the distal block 2 (P = 0.026, 0.042) that showed nominally significant (corrected P < 0.025) genotype × traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (P = 0.019) and rs242924 (P = 0.019). In block 2, rs17689966 (P = 0.018) showed significant and rs173365 (P = 0.026) showed nominally significant, gene × environment (G × E) effects on alcoholism status. This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci.