domingo, 1 de abril de 2018

Genetic Risk Score is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population. - PubMed - NCBI

2018 Mar 21. pii: S0016-5085(18)30337-8. doi: 10.1053/j.gastro.2018.03.030. [Epub ahead of print]

Genetic Risk Score is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population.

Weigl K1, Thomsen H2, Balavarca Y3, Hellwege JN4, Shrubsole MJ5, Brenner H6.

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Abstract

BACKGROUND & AIMS:

The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population.

METHODS:

We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search. We obtained genetic data from 1043 participants (50-79 years old) in a screening colonoscopy study in Germany, recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non-advanced adenomas, and 500 without neoplasms). Each participant was assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced neoplasms and non-advanced adenoma according to GRS was calculated by multiple logistic regression. Risk advancement periods were calculated. We replicated our findings using data from a subset of the Tennessee Colorectal Polyp Study.

RESULTS:

An increased GRS was associated with higher prevalence of advanced neoplasms, but not non-advanced adenomas. Participants in the middle and upper tertile of GRSs had a 2.2-fold and 2.7-fold increase in risk, respectively, of advanced neoplasms compared to those in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% CI, 0.76-1.57) for non-advanced adenoma in the middle tertile and 1.05 (95% CI, 0.70-1.55) for non-advanced adenoma in the upper tertile. The ORs were largest for proximal advanced neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85-6.82) and the upper tertile (OR, 3.61; 95% CI 1.84-7.10). The risk advancement period for medium vs low GRS was 13.4 years (95% CI 4.8-22.0) and for high vs low GRS was 17.5 years (95% CI, 7.8-27.3).

CONCLUSIONS:

In a genetic analysis of participants in a CRC screening study in Germany, an increased GRS (based on CRC-associated SNPs) was associated with increased prevalence of advanced neoplasms. These findings might be used in defining risk-adapted screening ages.