scholarly journals Synergistic Effects of Genetic Variants of Glucose Homeostasis and Lifelong Exposures to Cigarette Smoking, Female Hormones, and Dietary Fat Intake on Primary Colorectal Cancer Development in African and Hispanic/Latino American Women

2021 ◽  
Vol 11 ◽  
Author(s):  
Su Yon Jung ◽  
Eric M. Sobel ◽  
Matteo Pellegrini ◽  
Herbert Yu ◽  
Jeanette C. Papp
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cigarette Smoking ◽  
Risk Prediction ◽  
Daily Intake ◽  
Female Hormones ◽  
Genome Wide ◽  
Genomic Study ◽  
Latino American ◽  
Long Lifetime

BackgroundDisparities in cancer genomic science exist among racial/ethnic minorities. Particularly, African American (AA) and Hispanic/Latino American (HA) women, the 2 largest minorities, are underrepresented in genetic/genome-wide studies for cancers and their risk factors. We conducted on AA and HA postmenopausal women a genomic study for insulin resistance (IR), the main biologic mechanism underlying colorectal cancer (CRC) carcinogenesis owing to obesity.MethodsWith 780 genome-wide IR-specific single-nucleotide polymorphisms (SNPs) among 4,692 AA and 1,986 HA women, we constructed a CRC-risk prediction model. Along with these SNPs, we incorporated CRC-associated lifestyles in the model of each group and detected the topmost influential genetic and lifestyle factors. Further, we estimated the attributable risk of the topmost risk factors shared by the groups to explore potential factors that differentiate CRC risk between these groups.ResultsIn both groups, we detected IR-SNPs in PCSK1 (in AA) and IFT172, GCKR, and NRBP1 (in HA) and risk lifestyles, including long lifetime exposures to cigarette smoking and endogenous female hormones and daily intake of polyunsaturated fatty acids (PFA), as the topmost predictive variables for CRC risk. Combinations of those top genetic- and lifestyle-markers synergistically increased CRC risk. Of those risk factors, dietary PFA intake and long lifetime exposure to female hormones may play a key role in mediating racial disparity of CRC incidence between AA and HA women.ConclusionsOur results may improve CRC risk prediction performance in those medically/scientifically underrepresented groups and lead to the development of genetically informed interventions for cancer prevention and therapeutic effort, thus contributing to reduced cancer disparities in those minority subpopulations.

scholarly journals Integrating genome-wide polygenic risk scores and non-genetic risk factors to develop and validate risk prediction models for colorectal cancer

2021 ◽  
Author(s):  
Sarah EW Briggs ◽  
Philip Law ◽  
James E East ◽  
Sarah Wordsworth ◽  
Malcolm Dunlop ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Risk Prediction ◽  
Genetic Risk ◽  
Prediction Models ◽  
Fold Increase ◽  
Risk Scores ◽  
Risk Prediction Models ◽  
Polygenic Risk ◽  
Genome Wide

Objective While population screening programs for cancer colorectal (CRC) have proven benefit, risk-stratified approaches may improve screening outcomes further. To date, genome-wide polygenic risk scores (PRS) for CRC have not been integrated with non-genetic risk factors. We aimed to evaluate several genome-wide approaches, and the benefit of adding PRS to the QCancer-10 (colorectal cancer) non-genetic risk model, to identify those at highest risk of CRC. Design Using UK Biobank we developed and compared six different PRS for CRC. The top-performing genome-wide and GWAS-significant PRS were then combined with QCancer-10 and performance compared to QCancer-10 alone. Results PRS derived using LDpred2 software performed best, with an odds-ratio per standard deviation of 1.58, and top age- and sex-adjusted C-statistic of 0.733 in logistic regression and 0.724 in Cox regression models in the Geographic Validation Cohort. Integrated QCancer-10+PRS models out-performed QCancer-10, with C-statistics of 0.730 and 0.693, and explained variation of 28.1% and 21.0% from QCancer-10+LDpred2 and QCancer-10 respectively in men; performance improvements in women were similar. Men in the top 20% of risk accounted for 47.6% of cases, and women 42.5% using QCancer-10+LDpred2 models, with a 3.49-fold increase in risk in men and 2.75-fold increase in women in the top 5% of risk, compared to average risk. Decision curve analysis showed that adding PRS to QCancer-10 improved net-benefit and interventions avoided across most probability thresholds. Conclusion Integrated QCancer-10+PRS models out-perform existing CRC risk prediction models. Evaluation of risk stratified screening using this approach in a bowel screening population could be warranted.

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 prediction models for colorectal cancer: a systematic review

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Michele Sassano ◽  
Marco Mariani ◽  
Gianluigi Quaranta ◽  
Roberta Pastorino ◽  
Stefania Boccia
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Systematic Review ◽  
Prediction Model ◽  
Risk Prediction ◽  
Genetic Variants ◽  
Prediction Models ◽  
Risk Prediction Models ◽  
Discriminatory Accuracy ◽  
Traditional Risk Factors

Abstract Background Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. Methods We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. Results We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. Conclusions Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.

scholarly journals Genetic Risk Factors for Colorectal Cancer in Multiethnic Indonesians

2019 ◽  
Author(s):  
Irawan Yusuf ◽  
Upik A. Miskad ◽  
Ronald E. Lusikooy ◽  
Arham Arsyad ◽  
Akram Irwan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cancer Risk ◽  
Genome Wide Association Study ◽  
Risk Model ◽  
Bayesian Variable Selection ◽  
Colorectal Cancer Risk ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

AbstractPurposeColorectal cancer is a common cancer in Indonesia, yet it has been understudied. We conduct a genome-wide association study focused on evaluation and discovery of colorectal cancer risk factors in Indonesians.MethodsWe administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique.ResultsWe replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk.ConclusionsThis work helps characterize the relationship between variants in theSCL22A3,SCG5,GREM1, andSTXBP5-AS1genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

scholarly journals Genetic architectures of proximal and distal colorectal cancer are partly distinct

Gut ◽  
2021 ◽  
pp. gutjnl-2020-321534
Author(s):  
Jeroen R Huyghe ◽  
Tabitha A Harrison ◽  
Stephanie A Bien ◽  
Heather Hampel ◽  
Jane C Figueiredo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Drug Targets ◽  
Genome Wide Association Study ◽  
Proximal Colon ◽  
European Ancestry ◽  
Molecular Characteristics ◽  
Genome Wide ◽  
Mechanisms Of Carcinogenesis ◽  
Meta Analyses

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.ResultsWe identified 13 loci that reached genome-wide significance (p<5×10−8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.ConclusionGenetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

scholarly journals Association between known risk factors and colorectal cancer risk among Indigenous people participating in the Ontario Familial Colon Cancer Registry

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
S. Jamal ◽  
A.J. Sheppard ◽  
M. Cotterchio ◽  
S. Gallinger
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Colon Cancer ◽  
Risk Factor ◽  
Cancer Risk ◽  
Cigarette Smoking ◽  
Cancer Registry ◽  
Colorectal Cancer Risk ◽  
Indigenous Populations ◽  
Familial Colon Cancer

Introduction: Colorectal cancer is one of the most common cancers in Ontario and poses a high burden among many Indigenous populations. There are two aims for this short communication: (1) highlight colorectal risk factor findings from a population-based case-control study, (2) highlight trends and challenges of colorectal cancer research among Indigenous populations in Ontario.Methods: Prevalence of cigarette smoking, obesity, diet  and family history of colorectal cancer were estimated using the Indigenous identifier in the Ontario Familial Colon Cancer Registry (OFCCR) from 1999-2007 and then compared using age-adjusted odds ratio (with 95% confidence intervals) between cases and controls.Results: There were 66 Indigenous cases and 23 Indigenous controls. Cigarette smoking and obesity were higher in cases, but not statistically significant.Discussion and Conclusions: Findings were consistent with previous literature among Indigenous populations. Colorectal cancer risk factor and screening uptake information is limited among Indigenous populations; however, self-reported screening data suggest low colorectal screening uptake. Small sample size and poor Indigenous identification questions make it challenging to comprehensively understand cancer risk factors and burden in these populations.

scholarly journals Author Correction: Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Azmawati Mohammed Nawi ◽  
Siok Fong Chin ◽  
Luqman Mazlan ◽  
Rahman Jamal
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Trace Elements ◽  
Risk Prediction ◽  
Environmental Risk ◽  
Environmental Risk Factors ◽  
Serum Trace Elements

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