Working Paper Brief Report Version 1 This version is not peer-reviewed

IgG Mediates the Inverse Association between Age at Menarche and Breast Cancer

Version 1 : Received: 29 October 2019 / Approved: 31 October 2019 / Online: 31 October 2019 (04:29:28 CET)

How to cite: Lu, M.; Shen, X.; Chen, X.; Liu, B. IgG Mediates the Inverse Association between Age at Menarche and Breast Cancer. Preprints 2019, 2019100361 Lu, M.; Shen, X.; Chen, X.; Liu, B. IgG Mediates the Inverse Association between Age at Menarche and Breast Cancer. Preprints 2019, 2019100361

Abstract

Early menarche is well known as a risk factor for breast cancer (BC), hallmarks of antibodies were reported to be involved in the carcinogenesis and development of BC. However, whether the antibodies mediate the association between early menarche and BC is unknown. Based on the public summary statistics from large-scale genome-wide association studies in European ancestry individuals, polygenic risk score analyses were used to investigate the role of immunoglobulins (IgA, IgM, IgG) in the association between age at menarche (AAM) and BC. The inverse association between AAM and BC was replicated in our study, effect on BC [log odds ratio, log (OR)] was equal to -0.059 per standard deviation (SD) of AAM (P=1.35×10-20). Regarding the three types of immunoglobulins, only the path via IgG is consistent with the inverse association between AAM and BC. The effect [log(OR)]) on IgG was 0.34 (P=1.47×10-9) per SD increase of AAM, and 1 unit increase of IgG was associated with lower BC risk [log(OR)=-0.14, P=0.002]. The effect of 1 SD increase of AAM on BMI was -0.024 (P=0.019), but increase in BMI was not significantly associated with BC risk [log(OR)=-0.75, P=0.128]. Our study suggestes that IgG mediates the inverse association between AAM and BC.

Subject Areas

age at menarche; breast cancer; immunoglobulins; polygenic risk score

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