Abstract
Estrogen-mimicking chemicals, such as cadmium, may be associated with increased susceptibility to hormone-dependent cancers, though supporting data are sparse, particularly for endometrial cancer. The Health and Environmental Exposure Research (HEER) study worked with the Arkansas Central Cancer Registry, Iowa Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed with endometrial cancer who were willing to be contacted for participation in our case control study. Voter registration lists from Iowa and Missouri were used to randomly select similarly aged women as represented in the case population. Participants were interviewed by telephone to obtain information on known or suspected endometrial risk factors. Urine kits were sent to participants for home collection and returned for analysis. Our case-control study consisted of 631 incident cases of endometrial cancer diagnosed from January 2010 to October 2012 and 879 age-matched population-based controls, ages 18–81 years (mean age 65 years). We quantified cadmium amounts in urine and standardized these values through creatinine adjustment. Using data from all survey completers, we developed a multivariable model for endometrial cancer. Creatinine-adjusted cadmium concentration was added to this model. Odds ratio (OR) and 95% confidence intervals (CIs) for endometrial cancer were calculated. After multivariable adjustment, higher creatinine-adjusted cadmium exposure was associated with a statistically significant increase of endometrial cancer risk (OR: 1.22; 95% CI: 1.03–1.44). Our results provide evidence that cadmium may increase the risk of endometrial cancer, possibly through estrogenic effects.
Highlights
Cadmium is a toxic, bioaccumulating, non-essential, and highly persistent metal with a variety of adverse health effects
SAS for Windows v9.4 (SAS Institute Inc., Cary, NC, USA) was used. Of those approached by the cancer registries (n = 2597) for permission to send their names to our study for potential enrollment, 29% of the names (m = 749) were sent to the call center for interviewing
Of 711 eligible cases 89% (n = 631) completed an interview. In comparison to those who declined to pass their names to our study from the cancer registries, those who passed their names were more likely to be White (94% versus 90%) or married or living with partner (66% versus 55%) and less likely to be diagnosed with endometrioid carcinoma (International Classification of Diseases for Oncology: 8380) (74% versus 78%)
Summary
Cadmium is a toxic, bioaccumulating, non-essential, and highly persistent metal with a variety of adverse health effects. Ali and colleagues demonstrated that cadmium exposure in mice affected the height of the uterine luminal epithelium in a dose-dependent manner They suggested that the effects of cadmium exposure was through non-classical estrogen receptor signaling [19]. In 2008, Akesson et al reported a significant association between endometrial cancer and cadmium intake based on assignment of cadmium exposure levels from a food frequency questionnaire [1]. The Health and Environmental Exposure Research (HEER) study aimed to investigate the association between endometrial cancer risk from cadmium exposure after adjusting for confounders in a population-based case-control study using cases from the Arkansas, Iowa and Missouri state cancer registries and age-matched controls from voter registration lists
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