Women with increased levels of cadmium, which mimics estrogen in the body, had a higher risk of endometrial cancer, according to a 5-year observational study published in PLOS One. Smoking increases cadmium levels, and the metal is found in certain foods such as shellfish.
“Endometrial cancer has been associated with estrogen exposure,” said lead author Jane A. McElroy, PhD, of the Missouri University School of Medicine, in a press release. “Because cadmium mimics estrogen, it may lead to an increased growth of the endometrium, contributing to an increased risk of endometrial cancer.”
The researchers identified 631 incident cases of endometrial cancer—from cancer registries in Arkansas, Iowa, and Missouri—diagnosed from 2010 to 2012. Among these, 86% had type I endometrial cancer, which are mostly endometrioid adenocarcinomas driven by hormonal mechanisms; and 14% had type II endometrial cancer, which are mostly clear cell or serous histology. For controls they included 879 healthy, age-matched women randomly selected from voter registration rolls in Missouri and Iowa (mean age, 65 years).
Participants completed a survey with over 200 questions on potential endometrial cancer risk factors. After the survey, they were sent kits for saliva and urine collection, which were analyzed for cadmium levels—498 patients with endometrial cancer (79%) and 545 controls (61%) returned urine specimens.
“When comparing the cadmium levels of the individuals with endometrial cancer to the control group, we found a statistically significant increased risk of the cancer associated with a woman’s cadmium levels,” McElroy said. “We found the rate of endometrial cancer incidence increased by 22% in individuals with increased cadmium levels.”
After multivariable adjustments, the researchers found that a doubling of cadmium exposure was associated with a significant increased endometrial cancer risk (odds ratio [OR], 1.22; 95% CI, 1.03–1.44).
“We all have cadmium present in our kidneys and livers, but smoking has been shown to more than double a person’s cadmium exposure,” McElroy said.
When the researchers excluded current smokers, the results remained significant (OR, 1.19; 95% CI, 1.01–1.41).
“To our knowledge, this is the first published report on cadmium exposure and endometrial cancer risk using urine as a biomarker for cadmium measurement,” they wrote. “Inconsistent observational studies using estimated cadmium exposure from self-reported dietary intake has brought the validity of food frequency questionnaires for cadmium estimation into question.”
The authors highlighted several limitations of their study, including low participation among women diagnosed with endometrial cancer (631 of 2,597 incident cases), as well as some case information that was self-reported and the possibility of selection and recall bias.
The researchers suggest that further studies use urinary cadmium as a biomarker.