A Danish nationwide study of risk factors associated with Type I and Type II endometrial cancer.

Objective: To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors.

Methods: Women with EC diagnosed during 2000-2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade.

Results: We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors.

Conclusions: Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.