Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia.
OBJECTIVE
Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity.


METHODS
The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63).


RESULTS
HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04).


CONCLUSIONS
Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.|Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.|Emerging Disease Epidemiology Unit, Institut Pasteur, Paris, France.
Yusuke
Y
Shimakawa
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.|Department of Hepatology, Imperial College London, London, UK.
Maud
M
Lemoine
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Christian
C
Bottomley
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.
Harr Freeya
HF
Njai
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.|The Gambia Hepatitis Intervention Study, IARC, c/o MRC Unit, The Gambia, Banjul, The Gambia.
Gibril
G
Ndow
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.
Abdoulie
A
Jatta
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.
Saydiba
S
Tamba
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.
Lamin
L
Bojang
Ministry of Health and Social Welfare, Banjul, The Gambia.
Makie
M
Taal
Edward Francis Small Teaching Hospital, The Gambia, Banjul, The Gambia.
Ousman
O
Nyan
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.|Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Umberto
U
D'Alessandro
Medical Research Council (MRC) Unit, The Gambia, Banjul, The Gambia.|The Gambia Hepatitis Intervention Study, IARC, c/o MRC Unit, The Gambia, Banjul, The Gambia.
Ramou
R
Njie
Department of Hepatology, Imperial College London, London, UK.
Mark
M
Thursz
International Agency for Research on Cancer (IARC), Lyon, France.
Andrew J
AJ
Hall
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001722:Birth Order; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D002353:Carrier State / Q000453:epidemiology* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D017325:Hepatitis B Vaccines / Q000627:therapeutic use; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000453:epidemiology* / Q000635:transmission; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008113:Liver Neoplasms / Q000453:epidemiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012307:Risk Factors
D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines
Africa; Hepatitis B; birth order; carcinoma; hepatocellular; infectious disease transmission; vertical