Sibship size, birth order and risk of nasopharyngeal carcinoma and infectious mononucleosis: a nationwide study in Sweden.
The aetiology of nasopharyngeal carcinoma (NPC) remains enigmatic in endemic and non-endemic areas. Early-life infection with Epstein-Barr virus (EBV) may predispose to NPC development, whereas delayed primary infection with EBV may cause infectious mononucleosis (IM).



We used Swedish population and health registers to investigate whether potential indicators of early EBV infection, such as birth order, sibship size, maternal age and paternal age, are related to the subsequent risks for NPC and IM. We conducted two nested case-control studies, one for each health outcome, based on 251 NPC case patients, 11 314 IM case patients and five population control subjects per case matched by birth year and sex. We used conditional logistic regression modelling to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for NPC and IM.



The multivariate-adjusted ORs of developing NPC increased with number of siblings; the ORs associated with having one, two and three or more siblings, compared with none, were 1.59 (95% CI = 0.97, 2.62), 1.94 (95% CI = 1.17, 3.22), and 2.03 (95% CI = 1.23, 3.35), respectively (Ptrend = 0.006). This increased risk of NPC was explained mainly by having older rather than younger siblings. In contrast, lower risks of IM were observed among individuals with an increasing number of older siblings, younger siblings and total siblings.



Early-life social environment, possibly related to EBV infection, contributes to NPC pathogenesis in non-endemic areas. This hypothesis is further supported by the clearly contrasting findings between NPC and IM.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA zhiwei.liu@ki.se.
Zhiwei
Z
Liu
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Fang
F
Fang
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Ellen T
ET
Chang
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Hans-Olov
HO
Adami
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Exponent Inc., Health Sciences Practice, Menlo Park, CA, USA, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Weimin
W
Ye
D000293:Adolescent; D000328:Adult; D001722:Birth Order; D002277:Carcinoma / Q000453:epidemiology* / Q000473:pathology; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006801:Humans; D007244:Infectious Mononucleosis / Q000453:epidemiology*; D016015:Logistic Models; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000473:pathology; D010331:Paternal Age; D012042:Registries; D012307:Risk Factors; D035781:Siblings; D012931:Social Environment; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
Birth order; Epstein-Barr virus; Sweden; infectious mononucleosis; nasopharyngeal carcinoma; sibship size