A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

Presence of Saccharomyces cerevisiae subsp. diastaticus in industry and nature and spoilage capacity of its vegetative cells and ascospores

Saccharomyces cerevisiae sub-species diastaticus (S. diastaticus) is the main fungal cause of spoilage of carbonated fermented beverages in the brewing industry. Here, prevalence of S. diastaticus in nature and breweries was assessed as well as the spoilage capacity of its vegetative cells and spores. S. diastaticus could only be enriched from 1 out of 136 bark and soil samples from the Netherlands, being the first described natural isolate of this yeast outside South America. On the other hand, it was identified by PCR and selective enrichment in 25 and 21 out of 54 biofilm samples from beer filling halls in Asia, Africa, Europe and North America. ITS sequencing revealed that S. cerevisiae (including S. diastaticus) represented <0.05% of fungal DNA in 17 out of 20 samples, while it represented 0.1, 2 and 32% in samples VH6, VH1 and VH3 respectively. Next, vegetative cells and ascospores of the natural S. diastaticus isolate MB523 were inoculated in a variety of beer products containing 0.0–5.0% alcohol (v/v). Ascospores spoiled all beer products, while vegetative cells did not grow in Radler lemon 0.0, Radler lime mint 0.0 and Radler lemon lime 0.0. Notably, vegetative cells could spoil these Radlers when they first had been grown in alcohol free beer either or not mixed with Radler lemon lime 0.0. Conversely, vegetative cells that had been grown in Radler lemon lime lost their spoilage potential of this beer product when they had grown in YPD medium for more than 24 h. In addition, it was shown that cells grown in alcohol free beer were more heat resistant than cells grown in YPD (D52 40 min and ≤ 10.3 min, respectively). Together, these data show that S. diastaticus is a less prevalent variant of S. cerevisiae in nature, while it accumulates in breweries in mixed biofilms. Data also show that both vegetative cells and spores can spoil all tested beer products, the latter cell type irrespective of its environmental history

Presence of Saccharomyces cerevisiae subsp. diastaticus in industry and nature and spoilage capacity of its vegetative cells and ascospores

Saccharomyces cerevisiae sub-species diastaticus (S. diastaticus) is the main fungal cause of spoilage of carbonated fermented beverages in the brewing industry. Here, prevalence of S. diastaticus in nature and breweries was assessed as well as the spoilage capacity of its vegetative cells and spores. S. diastaticus could only be enriched from 1 out of 136 bark and soil samples from the Netherlands, being the first described natural isolate of this yeast outside South America. On the other hand, it was identified by PCR and selective enrichment in 25 and 21 out of 54 biofilm samples from beer filling halls in Asia, Africa, Europe and North America. ITS sequencing revealed that S. cerevisiae (including S. diastaticus) represented <0.05% of fungal DNA in 17 out of 20 samples, while it represented 0.1, 2 and 32% in samples VH6, VH1 and VH3 respectively. Next, vegetative cells and ascospores of the natural S. diastaticus isolate MB523 were inoculated in a variety of beer products containing 0.0–5.0% alcohol (v/v). Ascospores spoiled all beer products, while vegetative cells did not grow in Radler lemon 0.0, Radler lime mint 0.0 and Radler lemon lime 0.0. Notably, vegetative cells could spoil these Radlers when they first had been grown in alcohol free beer either or not mixed with Radler lemon lime 0.0. Conversely, vegetative cells that had been grown in Radler lemon lime lost their spoilage potential of this beer product when they had grown in YPD medium for more than 24 h. In addition, it was shown that cells grown in alcohol free beer were more heat resistant than cells grown in YPD (D52 40 min and ≤ 10.3 min, respectively). Together, these data show that S. diastaticus is a less prevalent variant of S. cerevisiae in nature, while it accumulates in breweries in mixed biofilms. Data also show that both vegetative cells and spores can spoil all tested beer products, the latter cell type irrespective of its environmental history

Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition

Item does not contain fulltextBACKGROUND: Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. OBJECTIVE: We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. DESIGN: A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (alpha- and beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity. RESULTS: UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma beta-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC. CONCLUSIONS: Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC

Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.

Contains fulltext : 80627.pdf (publisher's version ) (Closed access)We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.

Contains fulltext : 71044.pdf (publisher's version ) (Closed access)We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7))

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene

European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene

Contains fulltext : 97884.pdf (publisher's version ) (Closed access)Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 x 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC