Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

Suleeporn Sangrajrang, Yasunori Sato, Hiromi Sakamoto, Sumiko Ohnami, Nan M. Laird, Thiravud Khuhaprema, Paul Brennan, Paolo Boffetta, Teruhiko Yoshida

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82 Citations (Scopus)

Abstract

Estrogen and its metabolites are believed to play important roles in breast cancer, and its determinants include both genetic and lifestyle factors. The objective of the study is to investigate the association of breast cancer risk in Thailand with genetic polymorphisms in several genes involved in estrogen synthesis and metabolism. Five hundred and seventy patients with histopathologically confirmed breast cancer and 497 controls were included in the present study. Forty single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2, CYP1B1, CYP17, CYP19, CYP2C9, CYP2C19, AhR, ESR1, PGR, ERRG, COMT, HSD17B1, HSD17B2, EPHX1 and NQO1 genes were genotyped. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression, which suggested an altered risk for the following SNPs [gene, odds ratio (OR) and 95% confidence interval are shown]: heterozygote carriers of rs4917623 [CYP2C19, OR = 1.38 (1.04-1.84)], rs2066853 [AhR, OR = 1.34 (1.02-1.76)] and rs1857407 [ERRG, (OR = 0.72 (0.55-0.96)]; homozygote carriers of rs762551 [CYP1A2, OR = 2.75 (1.47-5.14)], rs4917623 [CYP2C19, OR = 1.48 (1.00-2.19) and rs945453 [ERRG, OR = 1.66 (1.04-2.65)]. In addition, a stratified analysis by menopausal status indicated that the association of the CYP1A2 (rs762551) and CYP17 (rs743572) polymorphisms with breast cancer risk were mainly evident in premenopausal, while ERRG (rs1857407) was significant in postmenopausal women. These findings suggest that CYP1A2, CYP2C19, AhR, ERRG and CYP17 polymorphisms may play an important role in estrogen metabolism and modify individual susceptibility to breast cancer in Thai women.

Original languageEnglish
Pages (from-to)837-843
Number of pages7
JournalInternational Journal of Cancer
Volume125
Issue number4
DOIs
Publication statusPublished - 2009 Aug 15
Externally publishedYes

Keywords

  • Breast cancer
  • Estrogen metabolizing enzyme
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Sangrajrang, S., Sato, Y., Sakamoto, H., Ohnami, S., Laird, N. M., Khuhaprema, T., Brennan, P., Boffetta, P., & Yoshida, T. (2009). Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women. International Journal of Cancer, 125(4), 837-843. https://doi.org/10.1002/ijc.24434