Association Between Educational Attainment and the Risk of Gynecological Malignancies: A Mediation Mendelian...

Gynecological malignancies are a significant burden for women, yet the causal link between educational attainment and gynecological cancer risk, along with the mediators, remains unclear. Therefore, the mendelian randomization method was employed to investigate the association between educational attainment and endometrial cancer, ovarian cancer, cervical cancer, and vulvar cancer, and quantified the proportion of the relationship potentially mediated by intermediate risk factors.

Genetic variants (single nucleotide polymorphisms) were employed as tools, primarily employing the inverse-variance weighted method, supplemented by four other sensi-tivity methods. Mediation proportion (β₁×β₂/β) was calculated via bootstrapped 95% confidence interval.

Higher educational attainment (per SD) was associated with reduced risk of endometrial cancer (OR 0.71, 0.61-0.83), ovarian cancer (OR 0.84, 0.73-0.97), and cervical cancer (OR 0.60, 0.38-0.95). Education causally influenced 18 potential mediators. Body mass index (OR 1.89; 95% CI: 1.69-2.11), body fat percentage (OR 2.11; 95% CI: 1.48-3.00), age at menopause (OR 1.23; 95% CI: 1.10-1.38), fasting insulin (OR 2.07; 95% CI: 1.13-3.83), testosterone (OR 1.58; 95% CI: 1.38-1.82), and sex hormone-binding globulin (OR 0.83; 95% CI: 0.75-0.91) causally influenced endometrial cancer, explaining 42.23%, 41.67%, -11.05%, 35.84%, 8.80%, and 9.82% of education's total effect, respectively. Body mass index (OR 1.12; 95% CI: 1.02-1.24) and age at menopause (OR 1.12; 95% CI: 1.02-1.24) also had causal effects on ovarian cancer, mediating 15.16% and -12.03% of education's effect.

The mendelian randomization analysis reveals the potential causal mechanisms underlying the association between education and the risk of endometrial cancer and ovarian cancer. Interventions targeting obesity (body mass index and body fat percentage), age at menopause, fasting insulin, testosterone, and SHBG may reduce the incidence of endometrial cancer associated with lower educational levels. For ovarian cancer, intervention strategies targeting body mass index and age at menopause could be key to help prevent ovarian cancer. These public health interventions could help mitigate health disparities caused by social inequality.