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 1981-2008. 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) > 5 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.

Background

The strong female predominance of biliary tract cancer (BTC) may be related to reproductive factors. We aimed to clarify whether parity or age at first birth influence the risk of BTC.

Methods

This was a population-based, case-control study including Swedish female and male cases of cancer of the gallbladder (GBC), extra hepatic bile ducts (EHCC), or the ampulla of Vater (AVC) between 1960 and 2008. For each case, 10 age- and sex-matched controls were randomly selected. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders.

Results

In total, 1169 cases of GBC, 432 cases of EHCC and 295 cases of AVC were included. Multi- and nulliparous women and men had an increased risk of all tumor locations in the biliary tract compared to uniparous women and men, respectively. Whereas higher age at first birth was associated with a decreased risk of GBC in women, no such association was found in men. There were no clear differences in the risk of EHCC and AVC between women and men.

Conclusion

Sex hormones may play a role in the etiology of GBC. The associations between reproductive factors and EHCC and AVC are similar in women and men, which do not support the sex hormone hypothesis.