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Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis.

Publication ,  Journal Article
Zhai, X; Gao, J; Hu, Z; Tang, J; Qin, J; Wang, S; Wang, X; Jin, G; Liu, J; Chen, W; Chen, F; Wang, X; Wei, Q; Shen, H
Published in: BMC Cancer
May 25, 2006

BACKGROUND: Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk. METHODS: To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population. RESULTS: We found that the distribution of TS3'-UTR (1494del6) genotype frequencies were significantly different between the cases and controls (P = 0.026). Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35-0.97) but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82-1.46). Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks. CONCLUSION: These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings.

Duke Scholars

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

May 25, 2006

Volume

6

Start / End Page

138

Location

England

Related Subject Headings

  • Thymidylate Synthase
  • Thymidine
  • Tandem Repeat Sequences
  • Sequence Deletion
  • Reproductive History
  • Postmenopause
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Mutagenesis, Insertional
  • Middle Aged
 

Citation

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Zhai, X., Gao, J., Hu, Z., Tang, J., Qin, J., Wang, S., … Shen, H. (2006). Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis. BMC Cancer, 6, 138. https://doi.org/10.1186/1471-2407-6-138
Zhai, Xiangjun, Jun Gao, Zhibin Hu, Jinhai Tang, Jianwei Qin, Shui Wang, Xuechen Wang, et al. “Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis.BMC Cancer 6 (May 25, 2006): 138. https://doi.org/10.1186/1471-2407-6-138.
Zhai, Xiangjun, et al. “Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis.BMC Cancer, vol. 6, May 2006, p. 138. Pubmed, doi:10.1186/1471-2407-6-138.
Zhai X, Gao J, Hu Z, Tang J, Qin J, Wang S, Wang X, Jin G, Liu J, Chen W, Chen F, Wei Q, Shen H. Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis. BMC Cancer. 2006 May 25;6:138.

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

May 25, 2006

Volume

6

Start / End Page

138

Location

England

Related Subject Headings

  • Thymidylate Synthase
  • Thymidine
  • Tandem Repeat Sequences
  • Sequence Deletion
  • Reproductive History
  • Postmenopause
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Mutagenesis, Insertional
  • Middle Aged