domingo, 6 de noviembre de 2016

The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study. - PubMed - NCBI

The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study. - PubMed - NCBI

 2016 Oct 28. pii: jmedgenet-2016-104125. doi: 10.1136/jmedgenet-2016-104125. [Epub ahead of print]

The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study.

Evans DG1,2,3, Brentnall A4, Byers H2,3, Harkness E5, Stavrinos P2,3, Howell A1,6; FH-risk study Group, Newman WG2,3, Cuzick J4.

Abstract

BACKGROUND:

Breast cancer familial risk clinics offer screening and preventive strategies. While BRCA1/BRCA2 genetic testing provides important risk information for some women, panels of more common breast cancer risk genetic variants may have relevance to greater numbers of women with familial risk.

METHODS:

Three polygenic risk scores (PRS) based on 18 SNPs were investigated in a case-control study of women attending a familial risk clinic. PRS were derived from published general European population allele ORs and frequencies (18-SNPs (SNP18)). In women with BRCA1/BRCA2 mutations, 3 SNPs/13 SNPs, respectively, generated the PRS estimates. In total, 364 incident breast cancer cases (112 with BRCA1/2 mutations) were matched with 1605 controls (691 BRCA1/2) by age last mammogram and BRCA1/2 genetic test result. 87 women with cancer before attendance were also considered. Logistic regression was used to measure PRS performance through ORs per IQR and calibration of the observed to expected (O/E) logarithm relative risk when unadjusted and adjusted for phenotypic risk factors assessed by the Tyrer-Cuzick (TC) model.

RESULTS:

SNP18 was predictive for non-carriers of BRCA1/2 mutations (IQR OR 1.55, 95% CI 1.29 to 1.87, O/E 96%). Findings were unaffected by adjustment from TC (IQR OR 1.56, 95% CI 1.29 to 1.89) or when prior cancers were included (IQR OR 1.55, 95% CI 1.30 to 1.87). There was some evidence to support polygenic scores with weights for individuals with BRCA1/2 mutations (BRCA1 IQR OR 1.44, 95% CI 1.17 to 1.76; BRCA2 IQ OR 1.44, 95% CI 0.90 to 2.31).

CONCLUSIONS:

PRS may be used to refine risk assessment for women at increased familial risk who test negative/have low likelihood of BRCA1/2 mutations. They may alter the recommended prevention strategy for many women attending family history clinics.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

KEYWORDS:

BRCA1; BRCA2; Polygenic Risk Score (PRS); Single Nucleotide Polymorphisms (SNPs); familial breast cancer

PMID:
 
27794048
 
DOI:
 
10.1136/jmedgenet-2016-104125

[PubMed - as supplied by publisher]


Public Health Genomics Knowledge Base (v1.2)

Genomics & Health Impact Update banner with DNA in background



Last Posted: Nov-04-2016 2PM






Last Updated: Nov 04, 2016

CDC Resources with and image of DNA

Seletced Insights & Reviews with various images of researchers in labortory environments

Epidemiology with an image of a crowd of people with a double helix

Translational Research with two images of people talking to a genetic counselor and an image of a hand with wrapped sequecing around it

Evidence Synthesis with an image of sequencing and a double helix

Practice & Implementation with images of people taking to a doctor and a nurse examining a child

Relevant Resources

Publicado por en

No hay comentarios:

Publicar un comentario

Suscribirse a: Enviar comentarios (Atom)