Exogenous estrogen and the risk of biliary tract cancer – a population-based study in a cohort of Swedish men treated for prostate cancer

Abstract

Background: To assess the role of exogenous estrogen in the etiology of biliary tract cancer, a nationwide population-based cohort study in Sweden was performed. Methods: The study included all men in Sweden with prostate cancer diagnosed in 1961-2008. Due to treatment standards, patients diagnosed in 1961-1980 were considered more exposed to estrogen, while those diagnosed in 1981-2008 were regarded less exposed. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated to estimate the risk of biliary tract cancer in cohort members compared to the corresponding Swedish male population. Results: After 849 307 person-years of follow-up in 203 131 prostate cancer patients, there were 41 incident gallbladder cancers and 36 cancers of the extra-hepatic bile ducts. In overall, there were no apparent differences in the risk of gallbladder cancer or bile duct cancer between patients diagnosed in 1961 -1980 and patients diagnosed in 1981 . However, in patients diagnosed in 1961 -1980, there was a statistically non-significant increased risk of gallbladder cancer (SIR 1.34; 95% CI 0.71-2.29) and extra-hepatic bile duct cancer (SIR 1.20; 95% CI 0.55-2.28)45 years of follow-up after the prostate cancer diagnosis. No such association was found for patients diagnosed in 1981-2008. Sensitivity analyses excluding prostate cancer patients exposed to potential confounding factors did not change the SIRs. Conclusions: Long exposure to high doses of exogenous estrogen might increase the risk of biliary tract cancer. However, any potential excess risk of bile duct cancer resulted by prolonged exposure to high doses of exogenous estrogen seems to be small.

Effects of Hydro-alcoholic Extract of Pumpkin Seeds on Oogenesis Pathway, Liver, and Kidney of Female Rats : The Effects of hydro-alcoholic extract of pumpkin

“…Infection, inflammation, and removal of gallbladder are more common in women taking oral estrogen, probably due to its hepatic effects. Estrogens enhance biliary cholesterol secretion and saturation, increase cholesterol in bile, and decrease gallbladder movement through the increase of crystallization in the bile (41)(42)(43).…”

“…Moreover, it can cause the excretion of excessive serum phosphorus in the urine. It is essential to know the amount of phosphorus and calcium intake to evaluate the effect of pumpkin seeds on the kidney since phosphorous precipitation in the kidneys can cause renal dysfunction (43). Therefore, future studies should investigate the effect of pumpkin seed extract on phosphorus and calcium intake and compare the results in adult and immature groups.…”

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

“…Increasing evidence has shown that gallbladder cancer is closely related to oestrogen. High levels of endogenous oestrogen and acquisition of exogenous oestrogen are all shown to exert a critical role on the incidence and prognosis of GBC . While ER signalling seems to be vital for gallbladder cancer, attention has not been paid to the current clinical treatment .…”

Increased ETV4 expression correlates with estrogen-enhanced proliferation and invasiveness of cholangiocarcinoma cells

“…Estrogen has been reported to stimulate proliferation of cholangiocytes and has been considered a factor in the pathogenesis of biliary tree disorders [ 17 – 21 ]. Other studies have suggested that bile duct obstruction is a cause of the high levels of serum estrogen in CCA patients and is a consequence of impairment of enzymes which convert estrogen metabolites [ 8 – 10 ].…”

“…Estrogen receptors (ERs) are found in normal biliary epithelial cells, and their expression is increased in CCA cells [ 9 , 17 ]. Moreover, exogenous estrogens have been considered a risk factor in the carcinogenesis of biliary tree cancer [ 21 ]. Thus E2 is a multifunctional hormone, making the identification of intermediate intracellular molecules involved in estrogen associated tumorigenesis challenging.…”