The incidence rates and relative risks for colorectal cancer (CRC) are higher in men than women. Sex steroids may play a role in this gender-associated difference in CRC risk. The present study was conducted to explore the relationship of single nucleotide polymorphisms in steroid hormone signalling (ESR1, ESR2, PGR, NR1I2 and SHBG), phase I- and II-metabolizing enzyme (COMT, HSD17B1, CYP1A1, CYP17A1, CYP1A2, CYP1B1, CYP2C9, CYP3A4, CYP2C19 and GSTP1) and hormone transporter (ABCB1) genes with risk of CRC in German women and men, separately. Forty-seven putatively functional single nucleotide polymorphisms were genotyped in 1798 CRC cases (746 women, 1052 men) and 1810 controls (732 women, 1078 men) from the population-based DACHS study (South Germany). Significant allele dose-response associations were observed with ESR2_rs1255998, ESR2_rs928554, HSD17B1_rs605059 and ABCB1_rs2229109 in women (p trend = 0.004, 0.05, 0.03 and 0.05, respectively) and with ABCB1_rs1045642, ABCB1_rs9282564 and SHBG_rs6259 in men (p trend = 0.01, 0.03 and 0.02, respectively). The ESR2_rs1255998_G allele showed the most significant association with risk for CRC in women, with a per-allele OR of 0.68 (95% CI 0.52-0.88). This finding was replicated in an independent study from North Germany including 1076 female CRC cases and 1151 controls (OR = 0.84, 95% CI 0.71-1.04), yielding a per-allele OR of 0.80 (95% CI 0.69-0.93, p trend = 0.003) in the pooled sample. These findings implicate a role of ESR2 in the risk for developing colorectal cancer in women and suggest that HSD17B1, ABCB1 and SHBG genes may contribute to sex steroid-mediated effects on CRC development.
Type of Publication:
Journal article published