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

Area of Science:

• Oncology
• Genetics
• Endocrinology

Background:

• The role of estrogen in colorectal cancer is debated.
• Estrogen receptor beta (ER-β) gene polymorphism (ESR2-CA) is a microsatellite with unknown function.
• Previous research linked shorter ESR2-CA alleles to altered colon cancer risk based on age.

Purpose of the Study:

• To investigate the pathobiological role of ESR2-CA genotype and ER-β expression in colorectal cancer.
• To analyze the association of ESR2-CA and ER-β with tissue type, age, and mismatch repair (MMR) protein status in postmenopausal women.

Main Methods:

• Examined ESR2-CA genotype and ER-β expression in cancerous (Ca) and non-cancerous (NonCa) tissues from 114 postmenopausal women.
• Categorized ESR2-CA alleles as 'S' (<22 repeats) and 'L' (≥22 repeats), forming SS, SL, and LL genotypes.
• Compared findings based on tissue type, age (≥70 vs. others), tumor location (right-sided), and MMR status (proficient vs. deficient).

Main Results:

• In non-cancerous tissue from women ≥70 years old, the SS genotype and higher ER-β expression were more frequent in right-sided tumors.
• ER-β expression was lower in cancerous tissue compared to non-cancerous tissue in proficient-MMR cases, but not in deficient-MMR cases.
• Non-cancerous tissue from SS genotype individuals showed higher ER-β expression than nSS genotypes, irrespective of cancer presence.

Conclusions:

• The germline ESR2-CA genotype and ER-β expression influence colon cancer characteristics, including age, tumor location, and MMR status.
• Findings support a role for ESR2-CA and ER-β in colon carcinogenesis, particularly in older women with right-sided tumors.
• The study highlights the interplay between genetic variations, hormone receptors, and molecular subtypes in colorectal cancer.