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

  • Shang Cao
  • Feiran Wei
  • Jinyi Zhou
  • Zheng Zhu
  • Wei Li
  • Ming WuEmail author
Epidemiology

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.

Keywords

Breast cancer Weight change CYP24A1 Single nucleotide polymorphisms 

Notes

Acknowledgements

We appreciate all study participants for their contributions. We thank the entire data collection team. Incident breast cancer cases and controls for this study were collected by Wuxi Center for Disease Control, Jiangsu Center for Disease Control.

Funding

This study was supported by World Cancer Research Fund (2011/RFA/473).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the ethical committee of the Jiangsu Center for Disease Control and Prevention (Jiangsu, China).

Informed consent

All participants signed a written informed consent.

Supplementary material

10549_2019_5484_MOESM1_ESM.docx (32 kb)
Supplementary material 1 (DOCX 32 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Epidemiology and Health StatisticsSoutheast UniversityNanjingChina
  2. 2.Department of OncologySoutheast UniversityNanjingChina
  3. 3.Department of Chronic Disease ControlJiangsu Provincial Center for Disease Control and PreventionNanjingChina

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