Reproductive Factors and the Risk of Hepatocellular Carcinoma in Women

The relationship between reproductive factors and the risk of primary liver cancer was analyzed using data of a case-control study conducted in Northern Italy between 1984 and 1991 on 79 women with histologically or serologically confirmed hepatocellular carcinoma and 344 controls in hospital for a wide spectrum of acute, non-neoplastic diseases. The multivariate relative risk (RR) for parous vs. nulliparous women was 2.6 (95% confidence interval (CI) 1.2 to 5.8), and the risk increased with parity from 2.1 for 1, to 2.6 for 2, to 3.2 for 3, to 3.5 for 4 or more births (chi 2(1) trend = 6.49, p = 0.01). The relative risks were above unity, though not significantly, in women reporting spontaneous (RR = 1.3) and induced (RR = 1.6) abortions, and there was a significant trend in risk with total number of abortions. An apparent inverse trend in risk with age and first birth was accounted for by parity. No relationship emerged with age at menarche, at menopause or other menstrual factors. The association between parity and hepatocellular carcinoma was, if anything, more marked at older ages, since the RR was 1.6 (95% CI 0.5 to 4.6) below age 60, and 4.8 (95% CI 1.3 to 18.1) at age 60 or over. This observation has relevant public-health implications, since in developed countries primary liver cancer is extremely rare among young women, but not at older ages. The association between parity and hepatocellular carcinoma is similar to that described for combined oral contraceptives, again confirming that the impact of contraceptives on the risk of several neoplasms is similar to that of pregnancy.