Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk

Chen, Xuechen; Li, Hengjing; Guo, Feng; Hoffmeister, Michael; Brenner, Hermann

doi:10.1016/j.eclinm.2022.101460

Cited by 24 publications

(19 citation statements)

References 34 publications

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“…Details of the lifestyle factors assessed in the DACHS study have been described in recent studies 11,[13][14][15][16] . Briefly, highly detailed information on current and prior smoking behavior, including years of initiation and cessation and amounts of smoking, was obtained from each participant and used to calculate pack-years for current smokers and former smokers (defined as people who had ever smoked and had ceased for at least 2 years).…”

Section: Data Collectionmentioning

confidence: 99%

“…The concept of GRE was developed in analogy with the well-established concept of risk and rate advancement periods 28 . Details on the calculation of GREs and 95% confidence intervals (CIs) for GREs have been published recently [11][12][13][14] . Briefly, consider an analysis based on a multivariable logistic regression:…”

Section: Derivation Of the Genetic Risk Equivalentmentioning

confidence: 99%

“…Therefore, whether and to what extent lifestyle factors interact with genetic risk, and to what extent increased polygenic risk can be offset by a healthy lifestyle, must crucially be demonstrated. Comparisons between the effects of individual lifestyle factors and polygenic risk have recently been conducted with the genetic risk equivalent (GRE), a novel metric to enhance effective risk communication in cancer preventive efforts [11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

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The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer

Chen

Ding

et al. 2022

Cancer Biol Med

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Objective: We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer (CRC) risk, to support effective risk communication for cancer prevention. Methods: A healthy lifestyle score (HLS) was derived from 5 lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body adiposity. The association of lifestyle and polygenic risk score (PRS) (based on 140 CRC-associated risk loci) with CRC risk was assessed with multiple logistic regression and compared through the genetic risk equivalent (GRE), a novel approach providing an estimate of the effects of adherence to a healthy lifestyle in terms of percentile differences in PRS. Results: A higher HLS was associated with lower CRC risk (4,844 cases, 3,964 controls). Those adhering to all 5 healthy lifestyle factors had a 62% (95% CI 54%–68%) lower CRC risk than those adhering to ≤ 2 healthy lifestyle factors. The estimated effect of adherence to all 5 compared with ≤ 2 healthy lifestyle factors was as strong as the effect of having a 79 percentile (GRE 79, 95% CI 61–97) lower PRS. The association between a healthy lifestyle and CRC risk was independent of PRS level but was particularly pronounced among those with a family history of CRC in ≥ 1 first-degree relative (P-interaction = 0.0013). Conclusions: A healthy lifestyle was strongly inversely associated with CRC risk. The large GRE indicated that CRC risk determined by polygenic risk may be offset to a substantial extent by adherence to a healthy lifestyle.

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Section: Data Collectionmentioning

confidence: 99%

Section: Derivation Of the Genetic Risk Equivalentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer

Chen

Ding

et al. 2022

Cancer Biol Med

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“…Epidemiology studies have observed significant correlations between long‐term use of antibiotic and risk of colorectal neoplasm 9‐11 . Studies investigating potentially modifiable risk factors for EOCRC have, however, focused on lifestyle factors and exposures occurring during adolescence and/or early adulthood and found associations with several factors such as obesity 12,13 and alcohol consumption 14 . There is thus limited evidence evaluating the effects of LRAU during early life on the risk of early‐onset colorectal neoplasm.…”

Section: Introductionmentioning

confidence: 99%

Association between antibiotic use during early life and early‐onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes

Jiang,

Boakye,

Sun

et al. 2023

Intl Journal of Cancer

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Early‐onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early‐life factors and EOCRC risk, with a particular focus on long‐term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC‐related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early‐onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early‐life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early‐onset CRC (OR = 1.48, 95% CI = 1.01‐2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17‐1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early‐onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79‐1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16‐2.64, P = .008, for TT genotype; Pinteraction = .089). Our study suggested that LRAU during early life is associated with increased risk of early‐onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome‐related pathway underlying colorectal carcinogenesis, are warranted.

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“…While the causes of these ‘sporadic’ EOCRC remain poorly understood, generational shifts in environment, lifestyle, and dietary habits have been strongly implicated [ 10 ]. For example, a recent study has provided evidence that moderate to high consumption of alcohol is associated with a greater risk of EOCRC than late onset CRC [ 11 ]. However, approximately one fifth of patients with EOCRC are affected by a hereditary cancer syndrome [ 4 ], which is about four times greater than the rates of these syndromes in CRC across all ages.…”

Section: Introductionmentioning

confidence: 99%

Insights into Early Onset Colorectal Cancer through Analysis of Normal Colon Organoids of Familial Adenomatous Polyposis Patients

Devall

Eaton

Ali

et al. 2022

Cancers

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Early onset colorectal cancer (EOCRC) rates have increased in recent decades. While lowering the recommended age for routine colonoscopies to 45 may reduce this burden, such measures do not address those who develop CRC before that age. Additional measures are needed to identify individuals at-risk for CRC. To better define transcriptomic events that precede the development of CRC, we performed RNA-sequencing analysis in colon organoids derived from seven healthy and six familial adenomatous polyposis (FAP) patients. This led to the identification of 2635 significant differentially expressed genes (FDR < 0.05). Through secondary analysis of publicly available datasets, we found that these genes were enriched for significant genes also present in FAP CRC and non-hereditary CRC datasets, including a subset that were unique to EOCRC. By exposing FAP colon organoids to a three-day ethanol treatment, we found that two EOCRC-relevant genes were also targets of CRC related lifestyle factors. Our data provides unique insight into the potential, early mechanisms of CRC development in colon epithelial cells, which may provide biomarkers for patient monitoring. We also show how modifiable lifestyle factors may further alter genes relevant to EOCRC, adding weight to the hypothesis that such factors represent an important contributor to increased EOCRC incidence.

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Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk

Cited by 24 publications

References 34 publications

The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer

The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer

Association between antibiotic use during early life and early‐onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes

Insights into Early Onset Colorectal Cancer through Analysis of Normal Colon Organoids of Familial Adenomatous Polyposis Patients

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