DUSP1 promoter methylation in peripheral blood leukocyte is associated with triple-negative breast cancer risk

Sci Rep. 2017 Feb 21:7:43011. doi: 10.1038/srep43011.

Abstract

DNA methylation is one of the most common epigenetic alterations, providing important information regarding cancer risk and prognosis. A case-control study (423 breast cancer cases, 509 controls) and a case-only study (326 cases) were conducted to evaluate the association of DUSP1 promoter methylation with breast cancer risk and clinicopathological characteristics. No significant association between DUSP1 methylation in peripheral blood leukocyte (PBL) DNA and breast cancer risk was observed. DUSP1 methylation was significantly associated with ER/PR-negative status; in particular, triple-negative breast cancer patients showed the highest frequency of DUSP1 methylation in both tumour DNA and PBL DNA. Soybean intake was significantly correlated with methylated DUSP1 only in ER-negative (OR 2.978; 95% CI 1.245-7.124) and PR negative (OR 2.735; 95% CI 1.315-5.692) patients. Irregular menstruation was significantly associated with methylated DUSP1 only in ER-positive (OR 3.564; 95% CI 1.691-7.511) and PR-positive (OR 3.902, 95% CI 1.656-9.194) patients. Thus, DUSP1 methylation is a cancer-associated hypermethylation event that is closely linked with triple-negative status. Further investigations are warranted to confirm the association of environmental factors, including fruit and soybean intake, irregular menstruation, and ER/PR status, with DUSP1 methylation in breast tumour DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • DNA Methylation* / drug effects
  • DNA, Neoplasm / metabolism
  • Dual Specificity Phosphatase 1 / genetics*
  • Dual Specificity Phosphatase 1 / metabolism
  • Eating
  • Female
  • Humans
  • Leukocytes / cytology
  • Leukocytes / metabolism*
  • Logistic Models
  • Menstruation
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Promoter Regions, Genetic
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Risk
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • DNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1