Effect of the Interaction Between Cadmium Exposure and CLOCK Gene Polymorphisms on Thyroid Cancer: a Case-Control Study in China

  • Qian Zhang
  • Chunxiao Jiang
  • Haibo Li
  • Chi Zhang
  • Huabing Wu
  • Fen HuangEmail author


The exposure to endocrine disruptors and the disruption of the circadian rhythms can both affect thyroid hormones, with results that are most likely carcinogenic in humans. The effects of cadmium (Cd) level and circadian-related single-nucleotide polymorphisms (SNPs) on thyroid cancer (TC) risk have rarely been reported. In this study, the associations of urine Cd, CLOCK gene polymorphisms, and TC risk were evaluated, in addition to the effect of the gene–environment interaction on TC risk. In this case-control study, 218 TC cases and 218 controls were enrolled. Cd in urinary samples was determined by atomic absorption spectrometry. Three SNPs (rs3805151, rs3805154, and rs78929565) were genotyped with an improved multiplex ligation detection reaction technique. The individuals with a high Cd level were 1.72-fold more likely to have TC (OR = 1.72, 95%CI 1.04–2.85), and a high Cd level was associated with higher tumor T stage and N stage (OR = 2.42, 95%CI 1.28–4.58; OR = 3.26, 95%CI 1.67–6.33, respectively). Individuals with TT genotype of rs78929565 had a 107 % increase in TC risk (OR = 2.07, 95%CI 1.00–4.29). Cases with CT genotype tended to have a higher AJCC stage (OR = 2.79, 95% CI 1.01–7.78). A significant interaction was detected between the rs78929565 variant and Cd exposure (p interaction = 0.04). The TT genotype carriers of rs78929565 with a high Cd level were more susceptible to thyroid cancer than the major homozygotes carriers who were exposed to a low cadmium level (OR = 2.66, 95%CI 1.07–6.59). These findings suggested that Cd exposure and the CLOCK variant genotypes were associated with TC risk and tumor severity. Individuals with minor allele of rs78929565 and higher Cd exposure had increased susceptibility to TC. Further studies are required to confirm these findings.


Cadmium Circadian rhythms Thyroid cancer CLOCK Polymorphism Gene–environment interaction 



We would like to thank all the subjects who participated in this research.

Authors’ Contributions

Study concept and design: Qian Zhang and Fen Huang. Acquisition of data: Qian Zhang, Huabing Wu. Analysis of data: Qian Zhang, Chunxiao Jiang and Haibo Li. Drafting and critical review of manuscript: Qian Zhang, Chunxiao Jiang, and Fen Huang

Funding Information

This work was supported by the Academic Aid Project for Top Talents (Professionals) in Colleges and Universities of Anhui Province (gxbjZD09) and the Project for Anhui Province Academic Technology Leader Reserve Candidates’ Academic Research Activities (2017H108).

Compliance with Ethical Standards

The present study was approved by the Anhui Medical University biomedical ethics committee. All subjects had written an informed consent form before participating in this study.

Conflict of Interest

The authors declare that there are no conflicts of interest.

Supplementary material

12011_2019_1904_MOESM1_ESM.pdf (64 kb)
Table S1 (PDF 64 kb)
12011_2019_1904_MOESM2_ESM.pdf (63 kb)
Table S2 (PDF 63 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 Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
  2. 2.Department of EpidemiologyCapital Institute of PediatricsBeijingChina
  3. 3.Central Laboratory of Preventive Medicine, School of Public HealthAnhui Medical UniversityHefeiChina
  4. 4.Laboratory for Environmental ToxicologyAnhui Medical UniversityHefeiChina

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