Evaluation of significant genome-wide association studies risk - SNPs in young breast cancer patients.

Michael Rath ,Ann H Partridge,Penelope Miron,Lidia Schapira,Steven E Come,Laura C Collins,Huili Li,Qiyuan Li,Kathryn J Ruddy,Mark Pomerantz,Bryce G Larson,Rulla M Tamimi,Sara Lindström,Alexander Miron,Hilde Vardeh,Elena F Brachtel ,Ji Heui Seo ,Matthew L Freedman ,Meghan E Meyer,Virginia F Borges ,Anne E Dowton

doi:10.1371/journal.pone.0216997

Abstract

PurposeGenome-wide-association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with an increased risk of breast cancer. Most of these studies were conducted primarily in postmenopausal breast cancer patients. Therefore, we set out to assess whether or not these breast cancer variants are also associated with an elevated risk of breast cancer in young premenopausal patients.MethodsIn 451 women of European ancestry who had prospectively enrolled in a longitudinal cohort study for women diagnosed with breast cancer at or under age 40, we genotyped 44 SNPs that were previously associated with breast cancer risk. A control group was comprised of 1142 postmenopausal healthy women from the Nurses’ Health Study (NHS). We assessed if the frequencies of the adequately genotyped SNPs differed significantly (p≤0.05) between the cohort of young breast cancer patients and postmenopausal controls, and then we corrected for multiple testing.ResultsGenotyping of the controls or cases was inadequate for comparisons between the groups for seven of the 44 SNPs. 9 of the remaining 37 were associated with breast cancer risk in young women with a p-value <0.05: rs10510102, rs1219648, rs13387042, rs1876206, rs2936870, rs2981579, rs3734805, rs3803662 and rs4973768. The directions of these associations were consistent with those in postmenopausal women. However, after correction for multiple testing (Benjamini Hochberg) none of the results remained statistically significant.ConclusionAfter correction for multiple testing, none of the alleles for postmenopausal breast cancer were clearly associated with risk of premenopausal breast cancer in this relatively small study.

Highlights

Each year, more than 10 000 women are diagnosed with breast cancer before the age of 40 in the United States alone [1, 2], and breast cancer is the most common cause of cancer-related death in women of this age [3]
In 451 women of European ancestry who had prospectively enrolled in a longitudinal cohort study for women diagnosed with breast cancer at or under age 40, we genotyped 44 single nucleotide polymorphisms (SNPs) that were previously associated with breast cancer risk
We assessed if the frequencies of the adequately genotyped SNPs differed significantly (p 0.05) between the cohort of young breast cancer patients and postmenopausal controls, and we corrected for multiple testing

Summary

Introduction

More than 10 000 women are diagnosed with breast cancer before the age of 40 in the United States alone [1, 2], and breast cancer is the most common cause of cancer-related death in women of this age [3]. Genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with an increased risk for the development of breast cancer in mostly postmenopausal patients [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25] Because most of these GWAS did not include a substantial number of women who were diagnosed with cancer while premenopausal, it has been unclear if the risk alleles discovered in postmenopausal women predispose to breast cancer at a young age. This study confirmed previous associations between increased breast cancer risk and SNPs in CASP8, TOX3 and ESR1

Methods

Results

Conclusion