scholarly journals A microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Janhavi R. Raut ◽  
Ben Schöttker ◽  
Bernd Holleczek ◽  
Feng Guo ◽  
Megha Bhardwaj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Prediction ◽  
Risk Score ◽  
Characteristic Curve ◽  
Predictive Ability ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Polygenic Scores

AbstractCirculating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

Abstract 881: Benchmarking genome-wide polygenic risk score development techniques in colorectal cancer risk prediction

2021 ◽  
Author(s):  
Minta Thomas ◽  
Lori C Sakoda ◽  
Jeffrey K Lee ◽  
Mark A Jenkins ◽  
Andrea Burnett-Hartman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Risk Score ◽  
Colorectal Cancer Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

scholarly journals Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mireia Obón-Santacana ◽  
Anna Díez-Villanueva ◽  
Maria Henar Alonso ◽  
Gemma Ibáñez-Sanz ◽  
Elisabet Guinó ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
General Population ◽  
Screening Program ◽  
Characteristic Curve ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Predictive Values ◽  
Polygenic Risk ◽  
Crc Screening

Abstract Background Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. Methods A PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation. Results The overall PRS range was 110–156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (ORD10vsD1 1.92, 95% CI 1.22–3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53–0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48–0.57). Conclusions PRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce.

scholarly journals Relative contributions of family history and a polygenic risk score on COPD and related outcomes: COPDGene and ECLIPSE studies

2020 ◽  
Vol 7 (1) ◽  
pp. e000755
Author(s):  
Matthew Moll ◽  
Sharon M. Lutz ◽  
Auyon J. Ghosh ◽  
Phuwanat Sakornsakolpat ◽  
Craig P. Hersh ◽  
...  
Keyword(s):  
Family History ◽  
Risk Score ◽  
Characteristic Curve ◽  
Significant Proportion ◽  
Chronic Obstructive ◽  
Polygenic Risk Score ◽  
Positive Interaction ◽  
Polygenic Risk ◽  
Mediation Analyses ◽  
The Impact

IntroductionFamily history is a risk factor for chronic obstructive pulmonary disease (COPD). We previously developed a COPD risk score from genome-wide genetic markers (Polygenic Risk Score, PRS). Whether the PRS and family history provide complementary or redundant information for predicting COPD and related outcomes is unknown.MethodsWe assessed the predictive capacity of family history and PRS on COPD and COPD-related outcomes in non-Hispanic white (NHW) and African American (AA) subjects from COPDGene and ECLIPSE studies. We also performed interaction and mediation analyses.ResultsIn COPDGene, family history and PRS were significantly associated with COPD in a single model (PFamHx <0.0001; PPRS<0.0001). Similar trends were seen in ECLIPSE. The area under the receiver operator characteristic curve for a model containing family history and PRS was significantly higher than a model with PRS (p=0.00035) in NHWs and a model with family history (p<0.0001) alone in NHWs and AAs. Both family history and PRS were significantly associated with measures of quantitative emphysema and airway thickness. There was a weakly positive interaction between family history and the PRS under the additive, but not multiplicative scale in NHWs (relative excess risk due to interaction=0.48, p=0.04). Mediation analyses found that a significant proportion of the effect of family history on COPD was mediated through PRS in NHWs (16.5%, 95% CI 9.4% to 24.3%), but not AAs.ConclusionFamily history and the PRS provide complementary information for predicting COPD and related outcomes. Future studies can address the impact of obtaining both measures in clinical practice.

Anorectal Malformations and the Risk of Colorectal Cancer—Is Early Routine Endoscopic Screening Indicated?

2020 ◽  
Author(s):  
Anna Svenningsson ◽  
Anna Gunnarsdottir ◽  
Tomas Wester
Keyword(s):  
Colorectal Cancer ◽  
Early Adulthood ◽  
Anorectal Malformations ◽  
Population Based ◽  
Observational Period ◽  
Endoscopic Screening ◽  
Medical Birth Register ◽  
National Patient ◽  
And Gender

Abstract Introduction Colorectal cancer (CRC) has been reported in early adulthood in patients with anorectal malformation (ARM), and therefore, the need of endoscopic controls has been discussed. The aim of this study was to assess the risk of CRC in patients with ARM. Materials and Methods This was a nationwide population-based study with data from Swedish national health care registers. All patients diagnosed with ARM born in Sweden between 1964 and 1999 were identified in the National Patient Register. The same group was followed up in the Swedish Cancer Register from birth to December 31, 2014, for occurrences of CRC. Five age- and gender-matched individuals randomly selected from the Medical Birth Register served as controls for each ARM patient born between 1973 and 1999. Results A total of 817 patients (474 males) with ARM were included and followed up from birth to the end of observational period. Time of follow-up ranged from 15 to 50 years (mean: 28 years). None of the patients was diagnosed with CRC during the observational period. One case of rectal cancer and one case of sigmoid cancer were detected among the 3,760 controls. Conclusion In our study, the risk of CRC in early adulthood in patients with ARM is low. Our result does not support routine endoscopic follow-up for patients with ARM during the first decade of life.

scholarly journals Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Author(s):  
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Early Onset ◽  
Low Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Pathogenic Variants ◽  
Predisposing Genes ◽  
The Mean ◽  
Early Onset Colorectal Cancer

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.

scholarly journals Validation of the Framingham hypertension risk score in a middle eastern population: Tehran lipid and glucose study (TLGS)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Koohi ◽  
Ewout W. Steyerberg ◽  
Leila Cheraghi ◽  
Alireza Abdshah ◽  
Fereidoun Azizi ◽  
...  
Keyword(s):  
Simple Model ◽  
Risk Score ◽  
Screening Tool ◽  
Middle Eastern ◽  
Predictive Ability ◽  
Eastern Population ◽  
Hypertension Risk ◽  
Graphical Comparison ◽  
Middle Eastern Population

Abstract Background The Framingham hypertension risk score is a well-known and simple model for predicting hypertension in adults. In the current study, we aimed to assess the predictive ability of this model in a Middle Eastern population. Methods We studied 5423 participants, aged 20–69 years, without hypertension, who participated in two consecutive examination cycles of the Tehran Lipid and Glucose Study (TLGS). We assessed discrimination based on Harrell’s concordance statistic (c-index) and calibration (graphical comparison of predicted vs. observed). We evaluated the original, recalibrated (for intercept and slope), and revised (for beta coefficients) models. Results Over the 3-year follow-up period, 319 participants developed hypertension. The Framingham hypertension risk score performed well in discriminating between individuals who developed hypertension and those who did not (c-index = 0.81, 95% CI: 0.79–0.83). Initially, there was a systematic underestimation of the original risk score (events predicted), which was readily corrected by a simple model revision. Conclusions The revised Framingham hypertension risk score can be used as a screening tool in public health and clinical practice to facilitate the targeting of preventive interventions in high-risk Middle Eastern people.

1134-P: Polygenic Risk Score of Type 2 Diabetes as a Predictive Factor for Macrovascular Complications: A Prospective Population-Based UK Biobank Study

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1134-P
Author(s):  
SANGHYUK JUNG ◽  
DOKYOON KIM ◽  
MANU SHIVAKUMAR ◽  
HONG-HEE WON ◽  
JAE-SEUNG YUN
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Predictive Factor ◽  
Population Based ◽  
Macrovascular Complications ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk

Initial participation as a predictor for continuous participation in population-based colorectal cancer screening

2017 ◽  
Vol 25 (3) ◽  
pp. 126-133 ◽  
Author(s):  
Deborah Saraste ◽  
Daniel J Öhman ◽  
Marika Sventelius ◽  
K Miriam Elfström ◽  
Johannes Blom ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Strong Predictor ◽  
Participation Rate ◽  
Occult Blood ◽  
Population Based ◽  
Faecal Occult Blood Testing ◽  
Faecal Occult

Objectives To assess patterns and probabilities of participation in multiple rounds of colorectal cancer screening. Methods All individuals who were invited to participate in population-based colorectal cancer screening in the Stockholm-Gotland region in Sweden between 1 January 2008 and 30 September 2015 were included in the study. Guaiac-based faecal occult blood testing was used. All individuals invited to the three first consecutive screening rounds were included in the analysis. Results There were 346,168 individuals eligible for invitation to screening. The average participation rate during the follow-up period was 60%. Eligible individuals could be invited 1–4 times, depending on age at first invitation. Of 48,959 individuals invited to the three first consecutive rounds of screening, 71% participated at least once, and 50% participated in all three rounds. Participation at first invitation was a predictor for participation in subsequent rounds, and the likelihood of continuous participation following participation in the first round was 84%. Of those who attended the first and second rounds, 93% also participated in the third round. Similar patterns of consistency were seen among non-participants. For individuals not participating in the first screening round, the likelihood of consistent non-participation was 71. Conclusions Participation in the first round of screening is a strong predictor for participation in subsequent rounds. Therefore, reducing barriers for initial participation is a key for achieving consistent participation over several rounds in organized colorectal cancer screening programmes.

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