title: Birth order and risk of nasopharyngeal carcinoma in multiplex families from Taiwan.
abstract: A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden. zhiwei.liu@ki.se.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, Maryland.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Coghill
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Wan-Lun
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, Maryland.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Westat, 1600 Research Blvd, Rockville, Maryland.
authors.forename: Shelley
authors.initials: S
authors.lastname: Niwa
authors.affiliation: Westat, 1600 Research Blvd, Rockville, Maryland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Brotzman
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, Maryland.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001722:Birth Order; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence; D012306:Risk; D035781:Siblings; D013624:Taiwan / Q000453:epidemiology
keywords: Epstein-Barr virus; Taiwan; birth order; infant-contact; multiplex family; nasopharyngeal carcinoma