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Article: Colorectal Cancer Study of Austria (CORSA): A Population-Based Multicenter Study

Gsur, Andrea / Baierl, Andreas / Brezina, Stefanie

Biology. 2021 July 28, v. 10, no. 8

2021

Abstract: The Colorectal cancer Study of Austria (CORSA) is comprised more than 13,500 newly diagnosed colorectal cancer (CRC) patients, patients with high- and low-risk adenomas as well as population-based controls. The recruitment for the CORSA biobank is ... ...

Abstract	The Colorectal cancer Study of Austria (CORSA) is comprised more than 13,500 newly diagnosed colorectal cancer (CRC) patients, patients with high- and low-risk adenomas as well as population-based controls. The recruitment for the CORSA biobank is performed in close cooperation with the invited two-stage CRC screening project “Burgenland PREvention trial of colorectal Disease with ImmunologiCal Testing” (B-PREDICT). Annually, more than 150,000 inhabitants of the Austrian federal state Burgenland aged between 40 and 80 are invited to participate using FIT-tests as an initial screening. FIT-positive tested participants are offered a diagnostic colonoscopy and are asked to take part in CORSA, sign a written informed consent, complete questionnaires concerning dietary and lifestyle habits and provide an ethylenediaminetetraacetic acid (EDTA) blood sample as well as a stool sample. Additional CRC cases have been recruited at four hospitals in Vienna and a hospital in lower Austria. A major strength of CORSA is the population-based controls who are FIT-positive and colonoscopy-confirmed to be free of polyps and/or CRC.
Keywords	EDTA (chelating agent) ; blood sampling ; colonoscopy ; colorectal neoplasms ; feces ; hospitals ; lifestyle ; Austria
Language	English
Dates of publication	2021-0728
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10080722
Database	NAL-Catalogue (AGRICOLA)

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Article: Colorectal Cancer Study of Austria (CORSA): A Population-Based Multicenter Study.

Gsur, Andrea / Baierl, Andreas / Brezina, Stefanie

Biology

2021 Volume 10, Issue 8

Abstract	The Colorectal cancer Study of Austria (CORSA) is comprised more than 13,500 newly diagnosed colorectal cancer (CRC) patients, patients with high- and low-risk adenomas as well as population-based controls. The recruitment for the CORSA biobank is performed in close cooperation with the invited two-stage CRC screening project "Burgenland PREvention trial of colorectal Disease with ImmunologiCal Testing" (B-PREDICT). Annually, more than 150,000 inhabitants of the Austrian federal state Burgenland aged between 40 and 80 are invited to participate using FIT-tests as an initial screening. FIT-positive tested participants are offered a diagnostic colonoscopy and are asked to take part in CORSA, sign a written informed consent, complete questionnaires concerning dietary and lifestyle habits and provide an ethylenediaminetetraacetic acid (EDTA) blood sample as well as a stool sample. Additional CRC cases have been recruited at four hospitals in Vienna and a hospital in lower Austria. A major strength of CORSA is the population-based controls who are FIT-positive and colonoscopy-confirmed to be free of polyps and/or CRC.
Language	English
Publishing date	2021-07-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10080722
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Article ; Online: Evaluation of the "Burgenland PREvention trial of colorectal cancer Disease with ImmunologiCal Testing" (B-PREDICT)-a population-based colorectal cancer screening program.

Brezina, Stefanie / Leeb, Gernot / Baierl, Andreas / Gräf, Evelyn / Hackl, Monika / Hofer, Philipp / Lang, Harald / Klein, Michaela / Mach, Karl / Schwarzer, Remy / Wlassits, Wilhelm / Püspök, Andreas / Gsur, Andrea

BMC gastroenterology

2024 Volume 24, Issue 1, Page(s) 149

Abstract: Background: The colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B- ... ...

Abstract	Background: The colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B-PREDICT was compared with the opportunistic screening colonoscopy (OPP-COL), performed in course of the nationwide screening program. Methods: Within B-PREDICT all residents of the Austrian federal state Burgenland, aged between 40 and 80 are annually invited to FIT testing. All individuals who underwent initial colonoscopy in Burgenland between 01/2003 and 12/2014, were included in this study. Individuals from the FIT-triggered invited screening program B-PREDICT were compared with those from the non-FIT triggered OPP-COL. Results: 15 133 individuals from B-PREDICT were compared to 10 045 individuals with OPP-COL. CRC detection rates were 1.34% (CI-95%, [1.15; 1.52]) in B-PREDICT compared to 0.54% in OPP-COL (95%-CI, [0.39; 0.68] p < 0.001). The decrease in the age standardized incidence rates of CRC was more pronounced in the population screened with FIT than in the general population screened with colonoscopy. Changes in incidence rates per year were -4.4% (95%-CI, [-5.1; -3.7]) vs. -1.8% (95%-CI, [-1.9; -1.6] p < 0.001). Conclusions: B-PREDICT shows a two-fold higher detection rate of CRC as well as HRA compared to OPP-COL.
MeSH term(s)	Humans ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/prevention & control ; Colorectal Neoplasms/epidemiology ; Colonoscopy/statistics & numerical data ; Early Detection of Cancer/methods ; Early Detection of Cancer/statistics & numerical data ; Male ; Middle Aged ; Aged ; Female ; Occult Blood ; Adult ; Austria/epidemiology ; Aged, 80 and over ; Incidence ; Mass Screening/methods ; Immunologic Tests/methods ; Feces/chemistry
Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Journal Article ; Evaluation Study
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-024-03242-7
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Article ; Online: Genome-wide association study of germline copy number variations reveals an association with prostate cancer aggressiveness.

Brezina, Stefanie / Feigl, Moritz / Gumpenberger, Tanja / Staudinger, Ricarda / Baierl, Andreas / Gsur, Andrea

Mutagenesis

2020 Volume 35, Issue 3, Page(s) 283–290

Abstract: Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and ...

Abstract	Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may help to guide clinical treatment decisions and reduce overtreatment. Previous research on genetic variations in prostate cancer has shown that germline copy number variations as well as somatic copy number alterations are commonly present in cancer patients, altering a greater portion of the cancer genome than any other type of genetic variation. To investigate the effect of germline copy number variations on cancer aggressiveness we have compared genome-wide screening data from genomic DNA isolated from the blood of 120 patients with aggressive prostate cancer, 231 patients with non-aggressive prostate cancer and 87 controls with benign prostatic hyperplasia from the Prostate Cancer Study of Austria biobank using the Affymetrix SNP 6.0 array. We could show that patients with an aggressive form of prostate cancer had a higher frequency of copy number variations [mean count of copy number segments (CNS) = 12.9, median count of CNS = 9] compared to patients with non-aggressive prostate cancer (mean count of CNS = 10.4, median count of CNS = 8) or control patients diagnosed with benign prostatic hyperplasia (mean count of CNS = 9.3, median count of CNS = 8). In general, we observed that copy number gain is a rarer event, compared to copy number loss within all three patient groups. Furthermore, we could show a significant effect of copy number losses located on chromosomes 8, 9 and 10 on prostate cancer aggressiveness (P = 0.040, P = 0.037 and P = 0.005, respectively). Applying a cross-validation analysis yielded an area under the curve of 0.63. Our study reports promising findings suggesting that copy number losses might play an important role in the establishment of novel biomarkers to predict prostate cancer aggressiveness at the time of diagnosis. Such markers could be used to facilitate risk stratification to reduce overtreatment of prostate cancer patients.
MeSH term(s)	Aged ; Austria ; Chromosomes, Human ; DNA Copy Number Variations ; Genetic Predisposition to Disease ; Genome, Human ; Genome-Wide Association Study ; Germ Cells/pathology ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/congenital ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; ROC Curve
Language	English
Publishing date	2020-04-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632903-2
ISSN	1464-3804 ; 0267-8357
ISSN (online)	1464-3804
ISSN	0267-8357
DOI	10.1093/mutage/geaa010
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Article ; Online: Using fecal immmunochemical cartridges for gut microbiome analysis within a colorectal cancer screening program.

Brezina, Stefanie / Borkovec, Martin / Baierl, Andreas / Bastian, Fabienne / Futschik, Andreas / Gasche, Nikolaus / Gruenberger, Thomas / Hallas, Michael / Jannsen, Christian / Leeb, Gernot / Lutz, Rebecca / Sladek, Barbara / Gsur, Andrea

Gut microbes

2023 Volume 15, Issue 1, Page(s) 2176119

Abstract: The colorectal cancer (CRC) screening program B-PREDICT is an invited two-stage screening project using a fecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. Since the gut microbiome likely plays ...

Abstract	The colorectal cancer (CRC) screening program B-PREDICT is an invited two-stage screening project using a fecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. Since the gut microbiome likely plays a role in the etiology of CRC, microbiome-based biomarkers in combination with FIT could be a promising tool for optimizing CRC screening. Therefore, we evaluated the usability of FIT cartridges for microbiome analysis and compared it to Stool Collection and Preservation Tubes. Corresponding FIT cartridges as well as Stool Collection and Preservation Tubes were collected from participants of the B-PREDICT screening program to perform 16S rRNA gene sequencing. We calculated intraclass correlation coefficients (ICCs) based on center log ratio transformed abundances and used ALDEx2 to test for significantly differential abundant taxa between the two sample types. Additionally, FIT and Stool Collection and Preservation Tube triplicate samples were obtained from volunteers to estimate variance components of microbial abundances. FIT and Preservation Tube samples produce highly similar microbiome profiles which cluster according to subject. Significant differences between the two sample types can be found for abundances of some bacterial taxa (e.g. 33 genera) but are minor compared to the differences between the subjects. Analysis of triplicate samples revealed slightly worse repeatability of results for FIT than for Preservation Tube samples. Our findings indicate that FIT cartridges are appropriate for gut microbiome analysis nested within CRC screening programs.
MeSH term(s)	Humans ; Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Early Detection of Cancer/methods ; Microbiota ; Colorectal Neoplasms/diagnosis ; Feces/microbiology
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2023.2176119
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Article ; Online: Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial

Trejo, Mario Jesus / Batai, Ken / Chen, Yuliang / Brezina, Stefanie / Chow, H-H Sherry / Ellis, Nathan / Lance, Peter / Hsu, Chiu-Hsieh / Pogreba-Brown, Kristen / Bishop, Maria / Gsur, Andrea / Jacobs, Elizabeth T.

Nutrition and Cancer. 2022 Dec. 13, v. 75, no. 1 p.143-153

2022

Abstract: Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic ... ...

Abstract	Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10⁻⁶) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10⁻⁶) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/β-catenin pathway leading to colorectal neoplasia. Trial Registration number: NCT00078897 (ClinicalTrials.gov).
Keywords	adenoma ; carcinogenesis ; case-control studies ; chemoprevention ; colorectal neoplasms ; genome-wide association study ; introns ; nutrition ; regression analysis ; risk ; selenium ; Austria
Language	English
Dates of publication	2022-1213
Size	p. 143-153.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	424433-3
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2022.2096910
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1496: Show issues

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Article ; Online: Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

Nutrition and cancer

2022 Volume 75, Issue 1, Page(s) 143–153

Abstract	Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of
MeSH term(s)	Humans ; Genome-Wide Association Study ; Case-Control Studies ; Selenium ; Adenoma/genetics ; Adenoma/prevention & control ; Colorectal Neoplasms/pathology ; Risk Factors ; Colonoscopy
Chemical Substances	Selenium (H6241UJ22B)
Language	English
Publishing date	2022-07-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	424433-3
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2022.2096910
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Article: Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas.

Gumpenberger, Tanja / Brezina, Stefanie / Keski-Rahkonen, Pekka / Baierl, Andreas / Robinot, Nivonirina / Leeb, Gernot / Habermann, Nina / Kok, Dieuwertje E G / Scalbert, Augustin / Ueland, Per-Magne / Ulrich, Cornelia M / Gsur, Andrea

Metabolites

2021 Volume 11, Issue 2

Abstract: Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely ... ...

Abstract	Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the "Metabolomic profiles throughout the continuum of colorectal cancer" (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the "Colorectal Cancer Study of Austria" (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.
Language	English
Publishing date	2021-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo11020119
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Article: The Immunome of Colon Cancer: Functional In Silico Analysis of Antigenic Proteins Deduced from IgG Microarray Profiling

Luna Coronell, Johana A / Sergelen, Khulan / Hofer, Philipp / Gyurján, István / Brezina, Stefanie / Hettegger, Peter / Leeb, Gernot / Mach, Karl / Gsur, Andrea / Weinhäusel, Andreas

Genomics, proteomics & bioinformatics. 2018 Feb., v. 16, no. 1

2018

Abstract: Characterization of the colon cancer immunome and its autoantibody signature from differentially-reactive antigens (DIRAGs) could provide insights into aberrant cellular mechanisms or enriched networks associated with diseases. The purpose of this study ... ...

Abstract	Characterization of the colon cancer immunome and its autoantibody signature from differentially-reactive antigens (DIRAGs) could provide insights into aberrant cellular mechanisms or enriched networks associated with diseases. The purpose of this study was to characterize the antibody profile of plasma samples from 32 colorectal cancer (CRC) patients and 32 controls using proteins isolated from 15,417 human cDNA expression clones on microarrays. 671 unique DIRAGs were identified and 632 were more highly reactive in CRC samples. Bioinformatics analyses reveal that compared to control samples, the immunoproteomic IgG profiling of CRC samples is mainly associated with cell death, survival, and proliferation pathways, especially proteins involved in EIF2 and mTOR signaling. Ribosomal proteins (e.g., RPL7, RPL22, and RPL27A) and CRC-related genes such as APC, AXIN1, E2F4, MSH2, PMS2, and TP53 were highly enriched. In addition, differential pathways were observed between the CRC and control samples. Furthermore, 103 DIRAGs were reported in the SEREX antigen database, demonstrating our ability to identify known and new reactive antigens. We also found an overlap of 7 antigens with 48 “CRC genes.” These data indicate that immunomics profiling on protein microarrays is able to reveal the complexity of immune responses in cancerous diseases and faithfully reflects the underlying pathology.
Keywords	antigens ; autoantibodies ; bioinformatics ; cell death ; colorectal neoplasms ; computer simulation ; databases ; genomics ; humans ; protein microarrays ; proteomics
Language	English
Dates of publication	2018-02
Size	p. 73-84.
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2240213-5
ISSN	2210-3244 ; 1672-0229
ISSN (online)	2210-3244
ISSN	1672-0229
DOI	10.1016/j.gpb.2017.10.002
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 6438: Show issues

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Article ; Online: Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis.

Culliford, Richard / Cornish, Alex J / Law, Philip J / Farrington, Susan M / Palin, Kimmo / Jenkins, Mark A / Casey, Graham / Hoffmeister, Michael / Brenner, Hermann / Chang-Claude, Jenny / Kirac, Iva / Maughan, Tim / Brezina, Stefanie / Gsur, Andrea / Cheadle, Jeremy P / Aaltonen, Lauri A / Dunlop, Malcom G / Houlston, Richard S

British journal of cancer

2021 Volume 124, Issue 6, Page(s) 1169–1174

Abstract: Background: Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we ... ...

Abstract	Background: Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods: We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (OR Results: No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (OR Conclusions: Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.
MeSH term(s)	Cholelithiasis/complications ; Cholelithiasis/epidemiology ; Cholelithiasis/genetics ; Colorectal Neoplasms/complications ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Prognosis ; Risk Factors ; United Kingdom/epidemiology
Language	English
Publishing date	2021-01-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-020-01211-x
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