In premenopausal women (N = 1157), current smoking was associated with lower CA125 (− 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5–10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. This evidence concerns the gene MUC16 and ovarian cancer.