Assessment of Interactions Between 205 Breast Cancer Susceptibility Loci and 13 Established Risk Factors in Relation to Breast Cancer Risk, in the Breast Cancer Association Consortium

Pooja Middha Kapoor,Sara Lindstrom,Sabine Behrens,Xiaoliang Wang,Kyriaki Michailidou,Manjeet K. Bolla,Qin Wang,Joe Dennis,Alison M. Dunning,Paul D. P. Pharoah,Marjanka K. Schmidt,Peter Kraft,Montserrat Garcia-Closas,Douglas F. Easton,Roger L. Milne,Jenny Chang-Claude

International journal of epidemiology（2020）SCI 1区

Cited 27|Views54

Abstract

Abstract Background Previous gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions. Methods Analyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions. Results Noteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10–4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10–5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth. Conclusions Overall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

Translated text

Key words

Gene-environment interaction,breast cancer,single nucleotide polymorphism,epidemiology,risk factors,Europeans

Bibtex

AI Read Science

AI Summary

AI Summary is the key point extracted automatically understanding the full text of the paper, including the background, methods, results, conclusions, icons and other key content, so that you can get the outline of the paper at a glance.

Example

Background

Key content

Introduction

Methods

Results

Related work

Fund

Key content

Pretraining has recently greatly promoted the development of natural language processing (NLP)
We show that M6 outperforms the baselines in multimodal downstream tasks, and the large M6 with 10 parameters can reach a better performance
We propose a method called M6 that is able to process information of multiple modalities and perform both single-modal and cross-modal understanding and generation
The model is scaled to large model with 10 billion parameters with sophisticated deployment, and the 10 -parameter M6-large is the largest pretrained model in Chinese
Experimental results show that our proposed M6 outperforms the baseline in a number of downstream tasks concerning both single modality and multiple modalities We will continue the pretraining of extremely large models by increasing data to explore the limit of its performance

Try using models to generate summary,it takes about 60s

Must-Reading Tree

Example

Generate MRT to find the research sequence of this paper