Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset

Song, Nan; Shin, Aesun; Park, Ji Won; Kim, Jeongseon; Oh, Jae Hwan

doi:10.1038/srep40644

Cited by 22 publications

(27 citation statements)

References 45 publications

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“…In addition, we performed multivariable and univariate cox regression analysis to elucidate the relationship between risk score and other factors like sex, age of diagnosis and Dukes stage. It was shown that risk score was the most significant among other factors [P=0.005 (multivarible) and P=0.001 (univariable)], while age (P=0.016) and adjuvant radiation therapy (P=0.021) were univariable factors to prognosis as reported ( 19 , 20 ) ( Table V upper). These data suggested that the risk score could predict patient survival directly and independently.…”

Section: Resultsmentioning

confidence: 89%

A five‑gene based risk score with high prognostic value in colorectal cancer

Pan

Zhang

et al. 2017

Oncol Lett

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Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC. The GSE14333 dataset containing survival information was then introduced in order to screen and verify prognosis-associated genes. Of the 66 DEGs, the present study screened out 46 biomarkers closely associated to patient overall survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was demonstrated that these genes participated in multiple biological processes which were highly associated with cancer proliferation, drug-resistance and metastasis, thus further affecting patient survival. The five most important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium voltage-gated channel a subunit 9 were selected by a random survival forests algorithm, and were further made up to a linear risk score formula by multivariable cox regression. Finally, the present study tested and verified this risk score within three independent GEO datasets (GSE14333, GSE17536 and GSE29621), and observed that patients with a high risk score had a lower overall survival (P<0.05). Furthermore, this risk score was the most significant compared with other predicting factors including age and American Joint Committee on Cancer stage, in the model, and was able to predict patient survival independently and directly. The findings suggest that this survival associated DEGs-based risk score is a powerful and accurate prognostic tool and is promisingly implemented in a clinical setting.

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Section: Resultsmentioning

confidence: 89%

A five‑gene based risk score with high prognostic value in colorectal cancer

Pan

Zhang

et al. 2017

Oncol Lett

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“…This hospital-based case-control study was conducted by the Korean National Cancer Center (NCC), as previously described in detail [ 43 , 44 ]. Briefly, among 1,427 eligible colorectal cancer patients who had been histologically confirmed and had given informed consent to participate in the study between 2010 and 2013, 703 patients were included in the study after applying the following exclusion criteria: failure to contact (N=168), patient refusal to participate after the recruitment (N=189), and incomplete questionnaires and/or insufficient blood samples for genotyping (N=367).…”

Section: Methodsmentioning

confidence: 99%

“…At enrollment, face-to-face interviews were conducted by trained interviewers with colorectal cancer cases by using a structured written questionnaire. Controls were asked to complete a self-administered questionnaire and were called by interviewers to confirm the responses, as detailed elsewhere [ 43 , 44 ]. The questionnaire collected general and lifestyle information regarding family history of colorectal cancer, education level, marital status, and alcohol drinking, smoking, and regular exercise habits.…”

Section: Methodsmentioning

confidence: 99%

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

Song

Shin

et al. 2018

Oncotarget

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BackgroundGenome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted.ResultsHigher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; ptrend<0.01). SNP rs6687758 near the DUSP10 gene at 1q41 had a statistically significant interaction with alcohol consumption in analyses of standardized drinks (p=4.6×10-3), although this did not surpass the corrected threshold for multiple testing. When stratified by alcohol consumption levels, in an additive model the risk of colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11).MethodsA total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms.ConclusionsOur results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer.

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“…The CRC patients were face-to-face interviewed by trained interviewers using a structured and written questionnaire (Additional file 1 ), which was also used in previous studies [ 11 – 13 ]. The original questionnaire written in Korean was developed based on questionnaires of the Korean National Health and Nutrition Examination survey (KNHANES) and the quality assurance and control of the national survey was described in elsewhere [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of interactions between common genetic variants and smoking on colorectal cancer

et al. 2017

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BackgroundAlthough genome-wide association studies (GWAS) have identified variants in approximately 40 susceptibility loci for colorectal cancer (CRC), there are few studies on the interactions between identified single-nucleotide polymorphisms (SNPs) and lifestyle risk factors. We evaluated whether smoking could modify associations between these genetic variants and CRC risk.MethodsA total of 703 CRC patients and 1406 healthy controls were included in this case-control study from the National Cancer Center in Korea. Thirty CRC susceptibility SNPs identified in previous GWAS were genotyped. A logistic regression model was used to examine associations between the SNPs and smoking behaviors by sex. The interaction was estimated by including an additional interaction term in the model.ResultsIn men, an increased CRC risk was observed for longer durations (OR>28 vs. ≤28years = 1.49 (95% CI = 1.11–1.98)), greater quantities (OR≥20 vs. <20cigarettes/day = 2.12 (1.61–2.79)), and longer pack-years of smoking (OR≥21 vs. <21pack-years = 1.78 (1.35–2.35)). In women, longer pack-years of smoking significantly increased CRC risk (OR≥5 vs. <5pack-years = 6.11 (1.10–34.00)). Moreover, there were significant interactions between smoking status and the polymorphisms rs1957636 at 14q22.3 (P interaction = 5.5 × 10−4) and rs4813802 at 20p12.3 (P interaction = 0.04) in men. Interactions between smoking status and the rs6687758 at 1q41 (P interaction = 0.03), duration and the rs174537 at 11q12.2 (P interaction = 0.05), and pack-years and the rs4813802 (P interaction = 0.04) were also found in women.ConclusionsAssociations between susceptibility SNPs and CRC risk may be modified by smoking behaviors, supporting the existence of gene-smoking interactions.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3886-0) contains supplementary material, which is available to authorized users.

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Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset

Cited by 22 publications

References 45 publications

A five‑gene based risk score with high prognostic value in colorectal cancer

A five‑gene based risk score with high prognostic value in colorectal cancer

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

Effects of interactions between common genetic variants and smoking on colorectal cancer

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