Prenatal biochemical screening and a woman’s long-term risk of cancer: a population-based cohort study

Background — Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman’s subsequent risk of hormone-sensitive cancer.

Methods — This population-based cohort study included women aged 12-55 years who underwent prenatal screening between 11+0 and 20+6 weeks’ gestation, in Ontario, Canada, 1993-2011, where universal healthcare is available. The hazard ratio (HR) of newly diagnosed breast, ovarian, endometrial and thyroid cancer – arising at ≥ 21+0 weeks’ gestation or thereafter – was estimated in association with abnormally low (≤ 5th) or high (> 95th) percentile multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol (uE3), pregnancy-associated plasma protein A (PAPP-A) and dimeric inhibin-A (DIA).

Results — Among 677,247 pregnant women, followed for a median of 11.0 years (IQR 7.5-16.1), 7231 (1.07%) developed breast cancer, 515 (0.08%) ovarian cancer, 508 (0.08%) endometrial cancer and 4105 (0.61%) thyroid cancer. In multivariable adjusted models, abnormally high hCG > 95th percentile MoM was associated with a doubling in the risk of endometrial cancer (aHR 1.98, 95% CI 1.33-2.95), while abnormally low AFP ≤ 5th percentile MoM conferred a moderately greater risk of thyroid cancer (aHR 1.21, 95% CI 1.07-1.38). Abnormally low PAPP-A ≤ 5th percentile MoM was not significantly associated with breast cancer after multivariable adjustment (aHR 1.19, 95% CI 0.98-1.36).

Conclusion — Women with abnormally high levels of serum hCG or low AFP in early pregnancy may be at greater future risk of certain types of hormone-sensitive cancers.