Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC.
Keywords: birth weight; epidemiology; liver cancer; prospective study; sex dimorphism.
© 2015 UICC.