Estrogen Receptor-β Gene Cytosine-Adenine (ESR2-CA) Repeat Polymorphism in Postmenopausal Colon Cancer

Int J Mol Sci. 2023 Feb 24;24(5):4502. doi: 10.3390/ijms24054502.

Abstract

The pathobiological role of estrogen is controversial in colorectal cancer. Cytosine-adenine (CA) repeat in the estrogen receptor (ER)-β gene (ESR2-CA) is a microsatellite, as well as representative of ESR2 polymorphism. Though its function is unknown, we previously showed that a shorter allele (germline) increased the risk of colon cancer in older women, whereas it decreased it in younger postmenopausal women. ESR2-CA and ER-β expressions were examined in cancerous (Ca) and non-cancerous (NonCa) tissue pairs from 114 postmenopausal women, and comparisons were made considering tissue types, age/locus, and the mismatch repair protein (MMR) status. ESR2-CA repeats <22/≥22 were designated as 'S'/'L', respectively, resulting in genotypes SS/nSS (=SL&LL). In NonCa, the rate of the SS genotype and ER-β expression level were significantly higher in right-sided cases of women ≥70 (≥70Rt) than in those in the others. A decreased ER-β expression in Ca compared with NonCa was observed in proficient-MMR, but not in deficient-MMR. In NonCa, but not in Ca, ER-β expression was significantly higher in SS than in nSS. ≥70Rt cases were characterized by NonCa with a high rate of SS genotype or high ER-β expression. The germline ESR2-CA genotype and resulting ER-β expression were considered to affect the clinical characteristics (age/locus/MMR status) of colon cancer, supporting our previous findings.

Keywords: ESR2-CA repeat polymorphism; age; colon cancer; estrogen; estrogen receptor-β; mismatch repair protein; postmenopausal women.

MeSH terms

  • Adenine
  • Aged
  • Colonic Neoplasms*
  • Cytosine
  • Estrogen Receptor beta / genetics
  • Female
  • Humans
  • Postmenopause
  • Receptors, Estrogen* / genetics

Substances

  • Receptors, Estrogen
  • Adenine
  • Cytosine
  • Estrogen Receptor beta
  • ESR2 protein, human