Reproductive factors in the etiology of hepatocellular carcinoma. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Data from a hospital-based case-control study conducted in four developing countries were analyzed to evaluate the role of reproductive factors in the etiology of liver cancer. Eighty-three patients newly diagnosed with primary liver cancer and 596 matched controls between the ages of 15 and 56 years completed study interviews. The relative risk of hepatocellular carcinoma was elevated significantly in women of high gravidity, an association that was attributable to the effects of full-term pregnancies. The adjusted relative-risk estimate in women who had ever had a full-term pregnancy was 1.6 (95 percent confidence interval = 0.6-4.1), and risk increased directly with the number of full-term pregnancies (P for trend = 0.03), rising to 3.8 among women with seven or more births compared to women with one to two births. Induced abortions and a history of miscarriage were unrelated to risk. These findings were unchanged after adjustment for a history of jaundice, lifetime number of sexual partners, or age at first sexual intercourse--variables which may be related to hepatitis B virus (HBV) exposure. Serum samples to determine HBV status were not collected, however, and it is not known whether the observed associations are independent of prior HBV infection.