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Published in: Breast Cancer Research and Treatment 2/2020

01-01-2020 | Breast Cancer | Epidemiology

The synergistic effect between adult weight changes and CYP24A1 polymorphisms is associated with pre- and postmenopausal breast cancer risk

Authors: Shang Cao, Feiran Wei, Jinyi Zhou, Zheng Zhu, Wei Li, Ming Wu

Published in: Breast Cancer Research and Treatment | Issue 2/2020

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Abstract

Purpose

Vitamin D (VD) metabolism regulates adipose tissue, lipogenesis inflammation, and tumor growth. CYP24A1 is the key enzyme for metabolic inactivation of active VD (1,25(OH)2D3). We examined whether common germline single nucleotide polymorphisms (SNPs) in the CYP24A1 gene could affect the association between adult weight gain and breast cancer (BC) risk.

Methods

The population-based case–control study included 818 patients with primary BC and 935 residence and age matched healthy controls. We studied the relationships between CYP24A1 gene SNPs (rs2209314, rs2585428, rs2762941, rs3787555, rs4809959, rs73913757, rs912505, and rs927a650), adult weight change and BC risk. Gene–weight change interactions were analyzed.

Results

Neither of CYP24A1 gene SNPs was associated with BC risk in the study participants. However, we found consistent gene–weight interactions with increasing adult weight gain for CYP24A1rs2762941 (P-interaction = 0.0089) and CYP24A1rs927650 (P-interaction = 0.0283). Adult weight gain has a higher premenopausal BC risk with double variant T alleles of rs927650 compared to women carrying at least one wild-type C allele (OR for TT = 1.82, 95% CI 1.10–3.01; for CT = 0.93, 95% CI 0.76–1.14; for CC = 1.12 95% CI 0.93–1.35). Women with double wild-type A alleles were at a higher postmenopausal BC risk compared to those carrying at least one variant-type G allele (OR for AA = 1.51, 95% CI 1.29–1.76; for AG = 1.13, 95% CI 0.98–1.30; for GG = 1.22 95% CI 0.95–1.57). When stratified by CYP24A1 SNPs genotypes, weight gain in adulthood increased postmenopausal BC risk of women with homozygous allele compared to women with heterozygotes allele.

Conclusion

Significant interactions of weight change with CYP24A1 polymorphisms suggest CYP24A1 as a potential link between weight change and BC risk and the possibility that the impact of adult weight gain on postmenopausal BC risk may be enhanced by homozygous alleles of CYP24A1 SNPs.
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Metadata
Title
The synergistic effect between adult weight changes and CYP24A1 polymorphisms is associated with pre- and postmenopausal breast cancer risk
Authors
Shang Cao
Feiran Wei
Jinyi Zhou
Zheng Zhu
Wei Li
Ming Wu
Publication date
01-01-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05484-6

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