Journal Article

DKFZ-2019-00624

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The association between weight at birth and breast cancer risk revisited using Mendelian randomisation.

Kar, S. P. ; Andrulis, I. L. ; Brenner, H.DKFZ* ; Burgess, S. ; Chang-Claude, J.DKFZ* ; Considine, D. ; Dörk, T. ; Evans, D. G. R. ; Gago-Domínguez, M. ; Giles, G. G. ; Hartman, M. ; Huo, D. ; Kaaks, R.DKFZ* ; Li, J. ; Lophatananon, A. ; Margolin, S. ; Milne, R. L. ; Muir, K. R. ; Olsson, H. ; Punie, K. ; Radice, P. ; Simard, J. ; Tamimi, R. M. ; Van Nieuwenhuysen, E. ; Wendt, C. ; Zheng, W. ; Pharoah, P. D. P.

2019
Springer Science + Business Media B.V. Dordrecht [u.a.]

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Please use a persistent id in citations: doi:10.1007/s10654-019-00485-7

Abstract: Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 × 10-8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio = 0.86 per 500 g higher BW; 95% confidence interval 0.73-1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer, but we are unable to rule out an association between the non-genetically-determined component of BW and breast cancer. Thus, genetically-predicted higher BW was not associated with an increased risk of breast cancer in adult life in our MR study.

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Contributing Institute(s):

1. Klinische Epidemiologie und Alternsforschung (C070)
2. Präventive Onkologie (C120)
3. Epidemiologie von Krebserkrankungen (C020)
4. DKTK Heidelberg (L101)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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