Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children

TY - JOUR

T1 - Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children

AU - Zimmermann, Esther

AU - Berentzen, Tina L.

AU - Gamborg, Michael

AU - Sørensen, Thorkild I A

AU - Baker, Jennifer L.

N1 - © 2015 UICC.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - 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. What's new? How do prenatal factors influence cancer risk? This study investigated how birth weight correlates with incidence of liver cancer among a cohort of over 200,000 individuals born between 1936 and 1980. Low birth weight, they found, means a boost in liver cancer risk for both men and women. Only in women did they observe an association between high birth weight and liver cancer. Thus it seems that a sex-specific mechanism may spur the molecular processes that start one down the path to liver cancer.

AB - 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. What's new? How do prenatal factors influence cancer risk? This study investigated how birth weight correlates with incidence of liver cancer among a cohort of over 200,000 individuals born between 1936 and 1980. Low birth weight, they found, means a boost in liver cancer risk for both men and women. Only in women did they observe an association between high birth weight and liver cancer. Thus it seems that a sex-specific mechanism may spur the molecular processes that start one down the path to liver cancer.

U2 - 10.1002/ijc.29900

DO - 10.1002/ijc.29900

M3 - Journal article

C2 - 26506514

SN - 0020-7136

VL - 138

SP - 1410

EP - 1415

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 6

ER -