Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Tumkur Sitaram, Raviprakash, Senior ResearcherORCID iD iconorcid.org/0000-0002-2391-5903
Alternative names
Publications (10 of 23) Show all publications
Tumkur Sitaram, R. & Ljungberg, B. (2024). Expression of HIF‑α and their association with clinicopathological parameters in clinical renal cell carcinoma. Upsala Journal of Medical Sciences, 129, Article ID e9407.
Open this publication in new window or tab >>Expression of HIF‑α and their association with clinicopathological parameters in clinical renal cell carcinoma
2024 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 129, article id e9407Article in journal (Refereed) Published
Abstract [en]

Objectives: This study aimed to assess the cellular localization and expression levels of hypoxia-inducible factor (HIF) -α proteins (specifically HIF-1α, HIF-2α, and HIF-3α) that play a role in the hypoxia pathway and to determine their correlation with clinicopathological parameters and patient survival in renal cell carcinoma (RCC).

Materials and methods: Tissue microarray (TMA) with cores from 150 clear cell RCCs and 31 non-ccRCC samples. HIF-1α, HIF-2α, and HIF-3α antibodies were used for immunohistochemistry (IHC) of TMA to evaluate the cellular localization and expression levels of HIF-α proteins, specifically in relation to the hypoxia pathway.

Results: The expression levels of the HIF-α proteins were higher in the nucleus than in the cytoplasm. Furthermore, the nuclear expression levels of all HIF-α proteins were significantly higher in clear cell RCC (ccRCC) than in non-ccRCC. Cytoplasmic HIF-3α expression was also higher in ccRCC than in non-ccRCC, whereas cytoplasmic HIF-1α and HIF-2α expression levels were similar between the different RCC types. In ccRCC, nuclear HIF-1α expression levels correlated with both nuclear HIF-2α and HIF-3α levels, whereas cytoplasmic HIF-3α expression levels were associated with HIF-1α only.In non-ccRCC, there was a positive correlation observed between nuclear HIF-1α and HIF-3α expression, but no correlation was found with HIF-2α. In patients with ccRCC, the nuclear expressions of HIF-1α and HIF-3α was significantly associated with cancer-specific survival (CSS) in univariate analysis. This association was no longer evident in multivariate analysis. Notably, there was no correlation observed between nuclear HIF-2α expression and CSS in these patients. In contrast, cytoplasmic expression levels showed no association with CSS.

Conclusion: The expression levels of the three primary HIF-α proteins were found to be higher in the nucleus than in the cytoplasm. Furthermore, the results indicated that HIF-3α and HIF-1α expression levels were significant univariate factors associated with CSS in patients with clear cell RCC. These results highlight the critical role that HIF-3α and HIF-1α play in the hypoxia pathway.

Place, publisher, year, edition, pages
Uppsala Medical Society, 2024
Keywords
renal cell carcinoma, ccRCC, non-ccRCC, HIF-1α, HIF-2α, HIF-3α, prognosis, tumor stage
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-223493 (URN)10.48101/ujms.v129.9407 (DOI)38571885 (PubMedID)2-s2.0-85190074794 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP19-976Lions Cancerforskningsfond i Norr, AMP20-1009
Available from: 2024-04-23 Created: 2024-04-23 Last updated: 2024-04-23Bibliographically approved
Sheng, N., Mårell, L., Tumkur Sitaram, R., Svensäter, G., Westerlund, A. & Strömberg, N. (2024). Human PRH1, PRH2 susceptibility and resistance and Streptococcus mutans virulence phenotypes specify different microbial profiles in caries. EBioMedicine, 101, Article ID 105001.
Open this publication in new window or tab >>Human PRH1, PRH2 susceptibility and resistance and Streptococcus mutans virulence phenotypes specify different microbial profiles in caries
Show others...
2024 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 101, article id 105001Article in journal (Refereed) Published
Abstract [en]

Background: Lifestyle- and sucrose-dependent polymicrobial ecological shifts are a primary cause of caries in populations with high caries prevalence. In populations with low prevalence, PRH1, PRH2 susceptibility and resistance phenotypes may interact with the Streptococcus mutans adhesin cariogenicity phenotype to affect caries progression, but studies are lacking on how these factors affect the microbial profile of caries.

Methods: We analysed how the residency and infection profiles of S. mutans adhesin (SpaP A/B/C and Cnm/Cbm) phenotypes and commensal streptococci and lactobacilli influenced caries progression in a prospective case–referent sample of 452 Swedish adolescents with high (P4a), moderate (P6), and low (P1) caries PRH1, PRH2 phenotypes. Isolates of S. mutans from participants were analysed for adhesin expression and glycosylation and in vitro and in situ mechanisms related to caries activity.

Findings: Among adolescents with the resistant (P1) phenotype, infection with S. mutans high-virulence phenotypes was required for caries progression. In contrast, with highly (P4a) or moderately (P6) susceptible phenotypes, caries developed from a broader polymicrobial flora that included moderately cariogenic oral commensal streptococci and lactobacilli and S. mutans phenotypes. High virulence involved unstable residency and fluctuating SpaP ABC, B-1, or Cnm expression/glycosylation phenotypes, whereas low/moderate virulence involved SpaP A phenotypes with stable residency. Adhesin phenotypes did not display changes in individual host residency but were paired within individuals and geographic regions.

Interpretation: These results suggest that receptor PRH1, PRH2 susceptibility and resistance and S. mutans adhesin virulence phenotypes specify different microbial profiles in caries. Funding: Swedish Research Council and funding bodies listed in the acknowledgement section.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Adhesion, Caries, Commensal pathogen, Host susceptibility, PRH1/PRH2, Streptococcus mutans
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-221645 (URN)10.1016/j.ebiom.2024.105001 (DOI)38364699 (PubMedID)2-s2.0-85185567071 (Scopus ID)
Funder
Swedish Research CouncilRegion VästerbottenSwedish Dental AssociationUmeå University
Available from: 2024-03-06 Created: 2024-03-06 Last updated: 2024-03-06Bibliographically approved
Tumkur Sitaram, R., Landström, M., Roos, G. & Ljungberg, B. (2021). Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status. Journal of Clinical Pathology, 74(4), 216-222
Open this publication in new window or tab >>Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status
2021 (English)In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 74, no 4, p. 216-222Article, review/survey (Refereed) Published
Abstract [en]

Renal cell carcinoma (RCC) includes diverse tumor types characterized by various genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, play a crucial role in the modification of signaling networks, tumor pathogenesis, and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe typesRCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of VHL gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including PTEN/PI3K/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signaling pathways directly or indirectly involved in ccRCC tumor progression, metastasis, angiogenesis, and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumor cells utilize alternate signaling pathways. This review compiles the state of knowledge about the PI3K/AKT signaling pathway confined to ccRCC and their cross-talks with VHL/HIF pathways.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2021
Keywords
ccRCC, PTEN, PI3K, VHL/HIF, signaling pathway
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:umu:diva-170709 (URN)10.1136/jclinpath-2020-206693 (DOI)000631874000007 ()32467322 (PubMedID)2-s2.0-85085755245 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP20- 1009
Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2023-09-05Bibliographically approved
Tumkur Sitaram, R., Landström, M., Roos, G. & Ljungberg, B. (2020). Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status. Clinical Oncology and Research, 3(3)
Open this publication in new window or tab >>Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status
2020 (English)In: Clinical Oncology and Research, ISSN 2613-4942, Vol. 3, no 3Article, review/survey (Refereed) Published
Abstract [en]

Renal cell carcinoma (RCC) encompasses various tumor types characterized by a variety of genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, can affect the signaling components and signaling networks, causing the modification of tumor pathogenesis and prognosis of RCC. The most prevalent RCC, clear cell RCC (ccRCC), is asymptomatic in the early stages, refractory to chemotherapy and radiation therapy, and has a poorer prognosis compared with the papillary and chromophobe ccRCC types. Loss of the VHL gene and upregulation of oxygen sensors, hypoxia-inducible factor alphas (HIF-α), which promote different growth factors, is a signature of sporadic ccRCC. The VHL-HIF-α and Wnt/β-catenin pathways are closely connected and contribute to the ontogeny of ccRCC. This review confines to ccRCC and the role of the Wnt/β-catenin signaling pathways and its crosstalk with VHL/HIF.

Keywords
ccRCC, VHL/HIF, Wnt/β-catenin signaling pathway
National Category
Cancer and Oncology
Research subject
Oncology; Urology
Identifiers
urn:nbn:se:umu:diva-170047 (URN)10.31487/j.COR.2020.03.09 (DOI)
Available from: 2020-04-23 Created: 2020-04-23 Last updated: 2020-04-27Bibliographically approved
Mallikarjuna, P., Tumkur Sitaram, R., Aripaka, K., Ljungberg, B. & Landström, M. (2019). Interactions between TGF-β type I receptor and hypoxia-inducible factor-alpha mediates a synergistic crosstalk leading to poor prognosis for patients with clear cell renal cell carcinoma. Cell Cycle, 18(17), 2141-2156
Open this publication in new window or tab >>Interactions between TGF-β type I receptor and hypoxia-inducible factor-alpha mediates a synergistic crosstalk leading to poor prognosis for patients with clear cell renal cell carcinoma
Show others...
2019 (English)In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 18, no 17, p. 2141-2156Article in journal (Refereed) Published
Abstract [en]

To investigate the significance of expression of HIF-1 alpha, HIF-2 alpha, and SNAIL1 proteins; and TGF-beta signaling pathway proteins in ccRCC, their relation with clinicopathological parameters and patient's survival were examined. We also investigated potential crosstalk between HIF-alpha and TGF-beta signaling pathway, including the TGF-beta type 1 receptor (ALK5-FL) and the intracellular domain of ALK5 (ALK5-ICD). Tissue samples from 154 ccRCC patients and comparable adjacent kidney cortex samples from 38 patients were analyzed for HIF-1 alpha/2 alpha, TGF-beta signaling components, and SNAIL1 proteins by immunoblot. Protein expression of HIF-1 alpha and HIF-2 alpha were significantly higher, while SNAIL1 had similar expression levels in ccRCC compared with the kidney cortex. HIF-2 alpha associated with poor cancer-specific survival, while HIF-1 alpha and SNAIL1 did not associate with survival. Moreover, HIF-2 alpha positively correlated with ALK5-ICD, pSMAD2/3, and PAI-1; HIF-1 alpha positively correlated with pSMAD2/3; SNAIL1 positively correlated with ALK5-FL, ALK5-ICD, pSMAD2/3, PAI-1, and HIF-2 alpha. Intriguingly, in vitro experiments performed under normoxic conditions revealed that ALK5 interacts with HIF-1 alpha and HIF-2 alpha, and promotes their expression and the expression of their target genes GLUT1 and CA9, in a VHL dependent manner. We found that ALK5 induces expression of HIF-1 alpha and HIF-2 alpha, through its kinase activity. Under hypoxic conditions, HIF-alpha proteins correlated with the activated TGF-beta signaling pathway. In conclusion, we reveal that ALK5 plays a pivotal role in synergistic crosstalk between TGF-beta signaling and hypoxia pathway, and that the interaction between ALK5 and HIF-alpha contributes to tumor progression.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
ALK5, clear cell renal cell carcinoma, HIF-α, SNAIL1, transforming growth factor-β
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-162654 (URN)10.1080/15384101.2019.1642069 (DOI)000478075700011 ()31339433 (PubMedID)2-s2.0-85070115115 (Scopus ID)
Available from: 2019-09-05 Created: 2019-09-05 Last updated: 2023-03-24Bibliographically approved
Laskar, R. S., Muller, D. C., Li, P., Machiela, M. J., Ye, Y., Gaborieau, V., . . . Scelo, G. (2019). Sex specific associations in genome wide association analysis of renal cell carcinoma. European Journal of Human Genetics, 27(10), 1589-1598
Open this publication in new window or tab >>Sex specific associations in genome wide association analysis of renal cell carcinoma
Show others...
2019 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 27, no 10, p. 1589-1598Article in journal (Refereed) Published
Abstract [en]

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-161383 (URN)10.1038/s41431-019-0455-9 (DOI)000485781600013 ()31231134 (PubMedID)2-s2.0-85068111474 (Scopus ID)
Available from: 2019-07-03 Created: 2019-07-03 Last updated: 2023-03-24Bibliographically approved
Johansson, M., Carreras-Torres, R., Scelo, G., Purdue, M. P., Mariosa, D., Muller, D. C., . . . Brennan, P. (2019). The influence of obesity-related factors in the etiology of renal cell carcinoma: A mendelian randomization study. PLoS Medicine, 16(1), Article ID e1002724.
Open this publication in new window or tab >>The influence of obesity-related factors in the etiology of renal cell carcinoma: A mendelian randomization study
Show others...
2019 (English)In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 16, no 1, article id e1002724Article in journal (Refereed) Published
Abstract [en]

Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.

Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.

Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

Place, publisher, year, edition, pages
Public Library of Science, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-155372 (URN)10.1371/journal.pmed.1002724 (DOI)000457349900005 ()30605491 (PubMedID)2-s2.0-85059499698 (Scopus ID)
Funder
NIH (National Institute of Health), R01 CA170298
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2022-10-31Bibliographically approved
Mallikarjuna, P., Tumkur Sitaram, R., Landström, M. & Ljungberg, B. (2018). VHL status regulates transforming growth factor-β signaling pathways in renal cell carcinoma. Oncotarget, 9(23), 16297-16310
Open this publication in new window or tab >>VHL status regulates transforming growth factor-β signaling pathways in renal cell carcinoma
2018 (English)In: Oncotarget, E-ISSN 1949-2553, Vol. 9, no 23, p. 16297-16310Article in journal (Refereed) Published
Abstract [en]

To evaluate the role of pVHL in the regulation of TGF-β signaling pathways in clear cell renal cell carcinoma (ccRCC) as well as in non-ccRCC; the expression of pVHL, and the TGF-β pathway components and their association with clinicopathological parameters and patient’s survival were explored. Tissue samples from 143 ccRCC and 58 non-ccRCC patients were examined by immunoblot. ccRCC cell lines were utilized for mechanistic in-vitro studies. Expression levels of pVHL were significantly lower in ccRCC compared with non-ccRCC. Non-ccRCC and ccRCC pVHL-High expressed similar levels of pVHL. Expression of the TGF-β type I receptor (ALK5) and intra-cellular domain were significantly higher in ccRCC compared with non-ccRCC. In non-ccRCC, expressions of ALK5-FL, ALK5-ICD, pSMAD2/3, and PAI-1 had no association with clinicopathological parameters and survival. In ccRCC pVHL-Low, ALK5-FL, ALK5-ICD, pSMAD2/3, and PAI-1 were significantly related with tumor stage, size, and survival. In ccRCC pVHL-High, the expression of PAI-1 was associated with stage and survival. In-vitro studies revealed that pVHL interacted with ALK5 to downregulate its expression through K48-linked poly-ubiquitination and proteasomal degradation, thus negatively controlling TGF-β induced cancer cell invasiveness. The pVHL status controls the ALK5 and can thereby regulate the TGF-β pathway, aggressiveness of tumors, and survival of the ccRCC and non-ccRCC patients.

Place, publisher, year, edition, pages
Impact Journals, LLC, 2018
Keywords
ccRCC, non-ccRCC, ALK5, pVHL, TGF-β signaling
National Category
Cancer and Oncology Cell and Molecular Biology
Research subject
molecular cell biology; Cancer Epidemiology
Identifiers
urn:nbn:se:umu:diva-146504 (URN)10.18632/oncotarget.24631 (DOI)2-s2.0-85044474424 (Scopus ID)
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2024-01-17Bibliographically approved
Machiela, M. J., Hofmann, J. N., Carreras-Torres, R., Brown, K. M., Johansson, M., Wang, Z., . . . Purdue, M. P. (2017). Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma. European Urology, 72(5), 747-754
Open this publication in new window or tab >>Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma
Show others...
2017 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 5, p. 747-754Article in journal (Refereed) Published
Abstract [en]

Background: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.

Objective: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.

Design, setting, and participants: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.

Outcome measurements and statistical analysis: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.

Results and limitations: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR = 2.07 per predicted kilobase increase, 95% confidence interval [CI]: = 1.70-2.53, p < 0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R-2 > 0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR = 1.73, 95% CI = 1.36-2.21, p < 0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N = 5573, OR = 1.93, 95% CI = 1.50-2.49, p < 0.0001), papillary (N = 573, OR = 1.96, 95% CI = 1.01-3.81, p = 0.046), and chromophobe RCC (N = 203, OR = 2.37, 95% CI = 0.78-7.17, p = 0.13).

Conclusions: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.

Patient summary: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
renal cell carcinoma, telomere length, genetic variants, mendelian randomization, risk
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-142908 (URN)10.1016/j.eururo.2017.07.015 (DOI)000412685300027 ()28797570 (PubMedID)2-s2.0-85026873779 (Scopus ID)
Note

Correction to affiliations for authors Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, and Cezary Cybulski in a corrected list, DOI: 10.1016/j.eururo.2018.05.017

Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2023-03-24Bibliographically approved
Scelo, G., Purdue, M. P., Brown, K. M., Johansson, M., Wang, Z., Eckel-Passow, J. E., . . . Chanock, S. J. (2017). Genome-wide association study identifies multiple risk loci for renal cell carcinoma. Nature Communications, 8, Article ID 15724.
Open this publication in new window or tab >>Genome-wide association study identifies multiple risk loci for renal cell carcinoma
Show others...
2017 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 8, article id 15724Article in journal (Refereed) Published
Abstract [en]

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P = 3.1 x 10(-10)), 3p22.1 (rs67311347, P = 2.5 x 10(-8)), 3q26.2 (rs10936602, P = 8.8 x 10(-9)), 8p21.3 (rs2241261, P = 5.8 x 10(-9)), 10q24.33-q25.1 (rs11813268, P = 3.9 x 10(-8)), 11q22.3 (rs74911261, P = 2.1 x 10(-10)) and 14q24.2 (rs4903064, P = 2.2 x 10(-24)). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-137038 (URN)10.1038/ncomms15724 (DOI)000402963900001 ()2-s2.0-85030655065 (Scopus ID)
Available from: 2017-06-28 Created: 2017-06-28 Last updated: 2023-03-28Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2391-5903

Search in DiVA

Show all publications