Sex- and tissue-specific effects of waterborne estrogen on estrogen receptor subtypes and E2-mediated gene expression in the reproductive axis of goldfish.

This research examined the gene expression profile of three goldfish estrogen receptor (ER) subtypes in multiple tissues in relation to mRNA levels of aromatase B and vitellogenin (VTG) following waterborne estrogen exposures. The protocol consisted of: i) adult male goldfish in late gonadal recrudescence exposed to 1 nM 17beta-estradiol (E2); ii) adult male and female goldfish in early sexual regression exposed to 1 nM E2 for 3, 6, 12 and 24h; and, iii) sexually mature, adult male goldfish exposed to 0.3 nM 17alpha-ethynylestradiol (EE2) for 24h. Liver produced the most consistent response with up-regulation of ERalpha in sexually regressed, mature and recrudescing males and in sexually regressed females. The dose and length of exposure, reproductive state and sex affected the auto-regulation of ERbeta1 by E2. ERbeta2 was not affected in any experiments suggesting it may not be auto-regulated by E2. Aromatase B and VTG gene expression were affected by E2, but also by other experimental conditions. EE2 induced liver ERalpha and VTG mRNA levels indicating that high environmental EE2 levels induce E2-mediated gene expression in a model teleost. These studies reveal a more complicated action of estrogenic compounds that has important implications on estrogenic endocrine disruptors in teleosts.

Risk of developing proximal versus distal colorectal cancer after a negative colonoscopy: a population-based study.

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) overall is reduced for up to 10 years after a negative colonoscopy. The objective of this research was to determine the incidence of proximal and distal CRC after a negative complete colonoscopy. METHODS: A cohort of Ontario residents aged 50 to 80 years who had a negative complete colonoscopy between January 1, 1992, and December 31, 1997, was identified by using linked administrative databases. Cohort members had no prior history of CRC, inflammatory bowel disease, or recent colonic resection. Each individual was followed up through December 31, 2005, and the relative rate (RR) of overall CRC, distal CRC, and proximal CRC was compared with the remaining Ontario population. RESULTS: A cohort of 110,402 individuals with a negative complete colonoscopy was identified. The RR of CRC overall and the RR of distal CRC remained significantly lower than the Ontario population. For example, at year 14 the RR of distal CRC was 0.21 (95% confidence interval, 0.05-0.36). The RR of proximal CRC was significantly lower than the Ontario population in half of the follow-up years, mainly after 7 years of follow-up. CONCLUSIONS: Over a 14-year follow-up period, negative complete colonoscopy was associated with a subsequent reduced incidence of CRC overall, and of incident CRC in the distal colon. However, the reduction in incidence of proximal CRC differed in magnitude and timing, and occurred in half the follow-up years, mainly after 7 years of follow-up. These results highlight an important limitation of colonoscopy in usual clinical practice.