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Breast Cancer Research and Treatment
Erschienen in: Breast Cancer Research and Treatment 2/2017

15.11.2016 | Epidemiology

Previous GWAS hits in relation to young-onset breast cancer

verfasst von: Min Shi, Katie M. O’Brien, Dale P. Sandler, Jack A. Taylor, Dmitri V. Zaykin, Clarice R. Weinberg

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

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Abstract

Purpose

Genome-wide association studies (GWAS) have identified dozens of single-nucleotide polymorphisms (SNPs) associated with breast cancer. Few studies focused on young-onset breast cancer, which exhibits etiologic and tumor-type differences from older-onset disease. Possible confounding by prenatal effects of the maternal genome has also not been considered.

Methods

Using a family-based design for breast cancer before age 50, we assessed the relationship between breast cancer and 77 GWAS-identified breast cancer risk SNPs. We estimated relative risks (RR) for inherited and maternally mediated genetic effects. We also used published RR estimates to calculate genetic risk scores and model joint effects.

Results

Seventeen of the candidate SNPs were nominally associated with young-onset breast cancer in our 1296 non-Hispanic white affected families (uncorrected p value <0.05). Top-ranked SNPs included rs3803662-A (TOX3, RR = 1.39; p = 7.0 × 10−6), rs12662670-G (ESR1, RR = 1.56; p = 5.7 × 10−4), rs2981579-A (FGFR2, RR = 1.24; p = 0.002), and rs999737-G (RAD51B, RR = 1.37; p = 0.003). No maternally mediated effects were found. A risk score based on all 77 SNPs indicated that their overall relationship to young-onset breast cancer risk was more than additive (additive-fit p = 2.2 × 10−7) and consistent with a multiplicative joint effect (multiplicative-fit p = 0.27). With the multiplicative formulation, the case sister’s genetic risk score exceeded that of her unaffected sister in 59% of families.

Conclusions

The results of this family-based study indicate that no effects of previously identified risk SNPs were explained by prenatal effects of maternal variants. Many of the known breast cancer risk variants were associated with young-onset breast cancer, with evidence that TOX3, ESR1, FGFR2, and RAD51B are important for young-onset disease.
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Metadaten
Titel
Previous GWAS hits in relation to young-onset breast cancer
verfasst von
Min Shi
Katie M. O’Brien
Dale P. Sandler
Jack A. Taylor
Dmitri V. Zaykin
Clarice R. Weinberg
Publikationsdatum
15.11.2016
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-4053-z

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