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Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10−8) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10−7). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to

Canadian Institutes of Health Research, Grant/ Award Number: 81274; Huntsman Cancer Institute Pilot Funds; Leukemia Lymphoma Society, Grant/Award Number: 6067-09; the National Institute of Health/National Cancer Institute, Grant/Award Numbers: P30 CA016672, P30 CA042014, P30 CA13148, P50 CA186781, R01 CA107476, R01 CA134674, R01 CA168762, R01 CA186646, R01 CA235026, R21 CA155951, R25 CA092049, R25 CA47888, U54 CA118948; Utah Population Database, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah State Department of Health, University of Utah; VicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414; Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer Database; Mayo Clinic Cancer Center; University of Pisa and DKFZ, The authors thank all site investigators that contributed to the studies within the Multiple Myeloma Working Group (Interlymph Consortium), staff involved at each site and, most importantly, the study participants for their contributions that made our study possible. This work was partially supported by intramural funds of University of Pisa and DKFZ. This work was supported in part by the National Institute of Health/National Cancer Institute (R25 CA092049, P30 CA016672, R01 CA134674, P30 CA042014, R01 CA186646, R21 CA155951, U54 CA118948, P30 CA13148, R25 CA47888, R01 CA235026, R01 CA107476, R01 CA168762, P50 CA186781 and the NCI Intramural Research Program), Leukemia Lymphoma Society (6067-09), Huntsman Cancer Institute Pilot Funds, Utah PopulationDatabase, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah StateDepartment of Health, University of Utah, Canadian Institutes of Health Research (Grant number 81274), VicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council (Grants 209057, 396414, 1074383), Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer Database and the Mayo Clinic Cancer Center.Open Access funding enabled and organized by ProjektDEAL., The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions., Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10(-7) either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients., Canadian Institutes of Health Research (CIHR) 81274, Huntsman Cancer Institute Pilot Funds, Leukemia and Lymphoma Society 6067-09, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) P30 CA016672 P30 CA042014 P30 CA13148 P50 CA186781 R01 CA107476 R01 CA134674 R01 CA168762 R01 CA186646 R01 CA235026 R21 CA155951 R25 CA092049 R25 CA47888 U54 CA118948, Utah Population Database, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah State Department of Health, University of Utah, VicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council 1074383 209057 396414, Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer Database, Mayo Clinic Cancer Center, University of Pisa, Helmholtz Association

The epidemiologic evidence regarding the relationship between alcohol consumption and multiple myeloma (MM) risk remains limited and inconsistent, although recent studies suggest a potential protective effect. We prospectively investigated the risk of MM in relation to alcohol consumption frequency among 499,292 participants enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study in 1995-1996. A total of 1,312 MM cases were identified during follow-up through December 2011. Hazard ratios (HR) and 95% confidence intervals (CI) for categories of alcohol consumption relative to those defined as light drinkers (

Analgesics are the most commonly consumed drugs worldwide. Evidence that analgesics increase kidney cancer risk has been mixed. We investigated the association between renal cell carcinoma (RCC) and analgesic use in a large population-based case-control study and a post-trial observational cohort study. Findings were used to update a recent meta-analytic review. We analyzed data from 1,217 RCC cases and 1,235 controls in the US Kidney Cancer Study and 98,807 participants in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO: n = 137 RCCs). Self-reported acetaminophen, aspirin and nonsteroid anti-inflammatory drug (NSAID) use and duration information was assessed in relation to RCC. For the US Kidney Cancer Study, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. For PLCO, we computed hazard ratios (HRs) and 95%CIs using Cox regression. Among case-control participants, RCC risk was associated with over-the-counter acetaminophen use (OR = 1.35, 95%CI = 1.01-1.83). There was a positive trend with increasing duration (p-trend = 0.01), with a two-fold risk for use ≥10 years (OR = 2.01, 95%CI = 1.30-3.12). No association with prescription acetaminophen use was detected. In PLCO, acetaminophen use was also associated with increased RCC risk (HR = 1.68, 95%CI = 1.19-2.39), although elevated risk was absent among the few long-term users. No association with RCC risk was detected for aspirin or NSAIDs use in either study. An association between acetaminophen use and kidney cancer was supported by meta-analytic cohort (n = 4; summary relative risk = 1.34; 95%CI = 1.13-1.59; p-heterogeneity = 0.40) and case-control (n = 9, summary OR = 1.20; 95%CI = 1.01-1.42; p-heterogeneity = 0.05) findings. In brief, acetaminophen use may increase the risk of developing RCC.