Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Montazeri, Zahra; Li, Xue; Nyiraneza, Christine; Ma, Xiangyu; Timofeeva, Maria; Svinti, Victoria; Meng, Xiangrui; He, Yazhou; Bo, Yacong; Morgan, Sam B.; Castellví–Bel, Sergi; Ruíz-Ponte, Clara; Fernández–Rozadilla, Ceres; Carracedo, Ángel; Castells, Antoni; Bishop, D. Timothy; Buchanan, Daniel D.; Jenkins, Mark A.; Keku, Temitope O.; Lindblom, Annika; Duijnhoven, Fränzel J.B. van; Wu, Anna H.; Farrington, Susan M.; Dunlop, Malcolm G.; Campbell, Harry; Τheodoratou, Evropi; Wang, Zheng; Little, Julian

doi:10.1136/gutjnl-2019-319313

Cited by 29 publications

(23 citation statements)

References 57 publications

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“…70-80% of cases of CRC occur sporadically and depend on risk factors that include history ulcerative colitis and Crohn's disease [ 2 ], but also constellation of modifiable environmental factors, more frequent in western countries, which include obesity, physical inactivity, poor diets, alcohol drinking, and smoking [ 3 ]. Approximately 25% of CRC patients have a positive family history of CRC, suggesting a specific contribution of inherited genetic factors [ 4 ]. Multiple whole-genome sequencing studies have been performed so far; however, only a small number of genetic variants have been successfully replicated in independent cohorts [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

Milanesi

Dobre

Bucuroiu

et al. 2020

Journal of Immunology Research

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microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC.

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Section: Introductionmentioning

confidence: 99%

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

Milanesi

Dobre

Bucuroiu

et al. 2020

Journal of Immunology Research

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“…We classified statistically significant associations that met the following criteria as ‘positive results’ [ 81 ]: (1) the P -value of Z-test is less than 0.05 in at least two gene models; (2) at the P -value level of 0.05, the FPRP is less than 0.2; (3) statistical power > 0.8; (4) I 2 < 50%. Considered as ‘less credible affirmation’ with lower threshold when the following conditions were met: (1) P -value <0.05 in at least one of the genetic models; (2) the statistical power was between 50 and 79% or FPRP > 0.2 or I 2 > 50%.…”

Section: Resultsmentioning

confidence: 99%

“…We classified statistically significant associations that met the following criteria as 'positive results' [81]: (1) the P-value of Z-test is less than 0.05 in at least two gene models; (2) at the P-value level of 0.05, the FPRP is less than 0.2;…”

Section: Credibility Of the Identified Genetic Associationsmentioning

confidence: 99%

Association between vitamin D receptorBsmI, FokI, andCdx2polymorphisms and osteoporosis risk: an updated meta-analysis

Chen

Zhu

et al. 2020

Bioscience Reports

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Background: Many studies have reported the association between vitamin D receptor (VDR) polymorphism and osteoporosis risk. However, their results were conflicting. Six previous meta-analyses have been published to analyze VDR BsmI, FokI, and Cdx2 polymorphisms on osteoporosis risk. However, they did not evaluate the reliability of statistically significant associations. Furthermore, a lot of new articles have been published on these themes, and therefore an updated meta-analysis was performed to further explore these issues. Objectives: To explore the association between VDR BsmI, FokI, and Cdx2 polymorphisms polymorphisms and osteoporosis risk. Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to evaluate the association between VDR BsmI, FokI, and Cdx2 polymorphisms and osteoporosis risk. To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) test and the Venice criteria. Results: Overall, statistically significantly increased osteoporosis risk was found in Indians and women for VDR FokI polymorphism. Statistically significantly decreased osteoporosis risk was found in West Asians for VDR BsmI polymorphism. However, when we performed an sensitivity analysis after excluding low quality and HWD studies, significantly decreased osteoporosis risk was only found in overall population for VDR BsmI polymorphism. Further, less-credible positive results were identified when we evaluated the credibility of positive results.</p> Conclusion: These positive findings should be interpreted with caution and indicate that significant association may most likely result from less-credible, rather than from true associations or biological factors on the VDR BsmI and FokI polymorphisms with osteoporosis risk.

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“…In recent years, an increasing number of susceptibility SNPs have been identified by genomewide association studies, which examine vast numbers of variants across the genome for associations with disease risk (16,17). Although each susceptibility SNP has a weak association with colorectal cancer risk, the cumulative association of many SNPs combined as a polygenic risk score (PRS) can result in a substantial risk gradient (in both directions) and is potentially an effective risk stratification method (14,18).…”

Section: Introductionmentioning

confidence: 99%

Ability of known colorectal cancer susceptibility SNPs to predict colorectal cancer risk: A cohort study within the UK Biobank

Gafni

Dite

Spaeth³

et al. 2021

Preprint

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Colorectal cancer risk stratification is crucial to improve screening and risk-reducing recommendations, and consequently do better than a one-size-fits-all screening regimen. Current screening guidelines in the UK, USA and Australia focus solely on family history and age for risk prediction, even though the vast majority of the population do not have any family history. We investigated adding a polygenic risk score based on 45 single-nucleotide polymorphisms to a family history model (combined model) to quantify how it improves the stratification and discriminatory performance of 10-year risk and full lifetime risk using a prospective population-based cohort within the UK Biobank. For both 10-year and full lifetime risk, the combined model had a wider risk distribution compared with family history alone, resulting in improved risk stratification of nearly 2-fold between the top and bottom risk quintiles of the full lifetime risk model. Importantly, the combined model can identify people (n=72,019) who do not have family history of colorectal cancer but have a predicted risk that is equivalent to having at least one affected first-degree relative (n=44,950). We also confirmed previous findings by showing that the combined full lifetime risk model significantly improves discriminatory accuracy compared with a simple family history model 0.673 (95% CI 0.664–0.682 versus 0.666 (95% CI 0.657–0.675), p=0.0065. Therefore, a combined polygenic risk score and first-degree family history model could be used to improve risk stratified population screening programs.

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Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Cited by 29 publications

References 57 publications

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

Association between vitamin D receptorBsmI, FokI, andCdx2polymorphisms and osteoporosis risk: an updated meta-analysis

Ability of known colorectal cancer susceptibility SNPs to predict colorectal cancer risk: A cohort study within the UK Biobank

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