Dataset Information

Head-to-Head Comparison of Family History of Colorectal Cancer and a Genetic Risk Score for Colorectal Cancer Risk Stratification.

ABSTRACT:

Objectives

Family history (FH) is associated with increased risk of colorectal cancer (CRC). We aimed to examine the potential for CRC risk stratification by known common genetic variants beyond FH in a large population-based case-control study from Germany.

Methods

Four thousand four hundred forty-seven cases and 3,480 controls recruited in 2003-2016 were included for whom comprehensive interview, medical, and genomic data were available. Associations with CRC risk were estimated from multiple logistic regression models for FH and a genetic risk score (GRS) based on 90 previously identified risk variants.

Results

CRC in a first-degree relative was associated with a 1.71-fold (95% confidence interval 1.47-2.00) increase in CRC risk. A higher risk increase (odds ratio 2.06, 95% confidence interval 1.78-2.39) was estimated for the GRS when it was dichotomized at a cutoff yielding the same positivity rate as FH among controls. Furthermore, the GRS provides substantial additional risk stratification in both people with and especially without FH. Equal or even slightly higher risks were observed for participants without FH with a GRS in the upper 20% compared with participants with FH with a GRS below median. The observed patterns were confirmed in a replication study.

Discussion

In contrast to common perception, known genetic variants do not primarily reflect some minor share of the familial excess risk of CRC, but rather reflect a substantial share of risk independent of FH.

SUBMITTER: Weigl K

PROVIDER: S-EPMC6970558 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Head-to-Head Comparison of Family History of Colorectal Cancer and a Genetic Risk Score for Colorectal Cancer Risk Stratification.

Weigl Korbinian K Hsu Li L Knebel Phillip P Hoffmeister Michael M Timofeeva Maria M Farrington Susan S Dunlop Malcolm M Brenner Hermann H

Clinical and translational gastroenterology 20191201 12

<h4>Objectives</h4>Family history (FH) is associated with increased risk of colorectal cancer (CRC). We aimed to examine the potential for CRC risk stratification by known common genetic variants beyond FH in a large population-based case-control study from Germany.<h4>Methods</h4>Four thousand four hundred forty-seven cases and 3,480 controls recruited in 2003-2016 were included for whom comprehensive interview, medical, and genomic data were available. Associations with CRC risk were estimated ...[more]

PMID: 31800541

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Project description:BackgroundPublished genetic risk scores for breast cancer (BC) so far have been based on a relatively small number of markers and are not necessarily using the full potential of large-scale Genome-Wide Association Studies. This study aimed to identify an efficient polygenic predictor for BC based on best available evidence and to assess its potential for personalized risk prediction and screening strategies.MethodsFour different genetic risk scores (two already published and two newly developed) and their combinations (metaGRS) were compared in the subsets of two population-based biobank cohorts: the UK Biobank (UKBB, 3157 BC cases, 43,827 controls) and Estonian Biobank (EstBB, 317 prevalent and 308 incident BC cases in 32,557 women). In addition, correlations between different genetic risk scores and their associations with BC risk factors were studied in both cohorts.ResultsThe metaGRS that combines two genetic risk scores (metaGRS2 - based on 75 and 898 Single Nucleotide Polymorphisms, respectively) had the strongest association with prevalent BC status in both cohorts. One standard deviation difference in the metaGRS2 corresponded to an Odds Ratio = 1.6 (95% CI 1.54 to 1.66, p = 9.7*10- 135) in the UK Biobank and accounting for family history marginally attenuated the effect (Odds Ratio = 1.58, 95% CI 1.53 to 1.64, p = 7.8*10- 129). In the EstBB cohort, the hazard ratio of incident BC for the women in the top 5% of the metaGRS2 compared to women in the lowest 50% was 4.2 (95% CI 2.8 to 6.2, p = 8.1*10- 13). The different GRSs were only moderately correlated with each other and were associated with different known predictors of BC. The classification of genetic risk for the same individual varied considerably depending on the chosen GRS.ConclusionsWe have shown that metaGRS2, that combined on the effects of more than 900 SNPs, provided best predictive ability for breast cancer in two different population-based cohorts. The strength of the effect of metaGRS2 indicates that the GRS could potentially be used to develop more efficient strategies for breast cancer screening for genotyped women.

Dataset Information

Head-to-Head Comparison of Family History of Colorectal Cancer and a Genetic Risk Score for Colorectal Cancer Risk Stratification.

Objectives

Methods

Results

Discussion

Publications

Head-to-Head Comparison of Family History of Colorectal Cancer and a Genetic Risk Score for Colorectal Cancer Risk Stratification.

Similar Datasets

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