Dataset Information

Smoking, Genetic Predisposition, and Colorectal Cancer Risk.

ABSTRACT:

Introduction

Smoking and genetic predisposition are established risk factors for colorectal cancer (CRC). We aimed to assess and compare their individual and joint impact on CRC risk using the novel approach of genetic risk equivalent (GRE).

Methods

Data were extracted from the Darmkrebs: Chancen der Verhütung durch Screening study, a large population-based case-control study in Germany. A polygenic risk score (PRS) based on 140 CRC-related single nucleotide polymorphisms was derived to quantify genetic risk. Multiple logistic regression was used to estimate the individual and joint impact of smoking and PRS on CRC risk, and to quantify the smoking effect in terms of GRE, the corresponding effect conveyed by a defined difference in PRS percentiles.

Results

There were 5,086 patients with CRC and 4,120 controls included. Current smokers had a 48% higher risk of CRC than never smokers (adjusted odds ratio 1.48, 95% confidence interval 1.27-1.72). A PRS above the 90th percentile was significantly associated with a 3.6-, 4.3-, and 6.4-fold increased risk of CRC in never, former, and current smokers, respectively, when compared with a PRS below the 10th percentile in never smokers. The interaction between smoking and PRS on CRC risk did not reach statistical significance (P = 0.53). The effect of smoking was equivalent to the effect of having a 30 percentile higher level of PRS (GRE 30, 95% confidence interval 18-42).

Discussion

Both smoking and the PRS carry essentially independent CRC risk information, and their joint consideration provides powerful risk stratification. Abstinence from smoking can compensate for a substantial proportion of genetically determined CRC risk.

SUBMITTER: Chen X

PROVIDER: S-EPMC7925134 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Smoking, Genetic Predisposition, and Colorectal Cancer Risk.

Chen Xuechen X Jansen Lina L Guo Feng F Hoffmeister Michael M Chang-Claude Jenny J Brenner Hermann H

Clinical and translational gastroenterology 20210301 3

<h4>Introduction</h4>Smoking and genetic predisposition are established risk factors for colorectal cancer (CRC). We aimed to assess and compare their individual and joint impact on CRC risk using the novel approach of genetic risk equivalent (GRE).<h4>Methods</h4>Data were extracted from the Darmkrebs: Chancen der Verhütung durch Screening study, a large population-based case-control study in Germany. A polygenic risk score (PRS) based on 140 CRC-related single nucleotide polymorphisms was deri ...[more]

PMID: 33646204

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Project description:BackgroundAlthough observational epidemiological studies have found that smoking is positively associated with risk of rheumatoid arthritis (RA), assessing the causality of this relationship has remained elusive because conventional observational studies are susceptible to bias such as confounding and reverse causation. Here, we applied the Mendelian randomization (MR) approach to examine the potential causal relationship between smoking and risk of RA.MethodsSummary statistics data for RA were obtained from a meta-analysis of genome-wide association studies (GWAS), including 14,361 RA cases and 43,923 controls of European ancestry. The instrumental variables (IV) and the genetic association estimates for smoking initiation and lifetime smoking were obtained from a GWAS meta-analysis including 1,232,091 individuals and a GWAS of 462,690 individuals of European ancestry, respectively. MR analyses were performed using the inverse-variance weighted (IVW) method and supplemented with the weighted-median method. Potential pleiotropy was assessed using the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression. Sensitivity analyses were further performed to test the robustness of the association.ResultsWe found that compared with never smokers, genetic predisposition to smoking initiation was positively associated with risk of RA (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15-1.52, P = 9.17 × 10-5 using the IVW method). Similarly, genetically predicted lifetime smoking was associated with an increased risk of RA (OR = 1.55, 95% CI = 1.13-2.14, P = 0.007). Sensitivity analyses using alternative MR methods and different sets of IVs produced similar results, suggesting the robustness of our findings.ConclusionsThese results provide support for a causal association between smoking and increased risk of RA. Further studies are warranted to explain the underlying mechanisms of smoking in the development of RA.

Project description:BackgroundPlant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk.MethodsThis prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model.ResultsOver a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81-0.96) and 0.91 (95% CI, 0.84-0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males.ConclusionsOur results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.

Dataset Information

Smoking, Genetic Predisposition, and Colorectal Cancer Risk.

Introduction

Methods

Results

Discussion

Publications

Smoking, Genetic Predisposition, and Colorectal Cancer Risk.

Similar Datasets

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