© 2005 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Birth Order, Atopy, and Risk of Non-Hodgkin Lymphoma
Affiliations of authors: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia (AEG, CMV); School of Public Health, The University of Sydney, Sydney, Australia (AK, BKA)
Correspondence to: Andrew E. Grulich, MBBS, MSc, PhD, University of New South Wales, National Center in HIV Epidemiology and Clinical Research, Level 2, 376 Victoria St., Darlinghurst, NSW 2010 Australia (e-mail: agrulich{at}nchecr.unsw.edu.au).
We recently reported (1) that early birth order is associated with a reduced risk of non-Hodgkin lymphoma (NHL). Although birth order reflects the number of older siblings, Kemp et al. suggest that examination of younger sibling numbers and birth intervals may provide insights into the timing and mechanism of the risk reduction. In a case–control study (2), these researchers found that increased exposure to younger siblings was associated with a reduced risk of multiple sclerosis (MS). In addition, because high Epstein-Barr Virus (EBV) antibody patterns were associated with exposure to younger siblings among the control subjects, they suggested that exposure to infection with EBV through younger siblings may decrease the risk of MS (2).
To assess whether a similar mechanism may operate for NHL, we have now evaluated our data for possible associations of NHL with numbers of older and younger siblings. We had asked participants about 1) their birth order and 2) how many siblings and other children regularly lived in the same household during childhood. For the analysis, we assumed that all children living in the same household were siblings because we could not distinguish siblings from other children living in the same household. We did not collect data on birth intervals.
As expected from our results on birth order (1), these analyses showed a statistically significant trend of increasing risk of NHL with increasing number of older siblings. The trend was not affected by adjustment for number of younger siblings. In addition, having younger siblings was not associated with NHL risk (Table 1).
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Thus, our results do not support the hypothesis that exposure to younger siblings influences NHL risk. Early childhood exposure to common, specific infective agents such as EBV is only one of the possible explanations for risk of NHL increasing with later birth order. It may not be infection with specific pathogens that is most important but rather the effects of very early commensal infection on the developing immune system (3). Our article (1) described very similar reductions in risk of NHL in only and other first-born children. A first born is effectively an only child until the birth of his or her first sibling. Taken together, the similarity of the risk reduction for both first-born and only children and the absence of an effect of exposure to younger siblings support the hypothesis that it is the presence of an exposure in infancy or very early childhood that increases the risk of NHL.
REFERENCES
(1) Grulich AE, Vajdic CM, Kaldor JM, Hughes AM, Kricker A, Fritschi L, et al. Birth order, atopy, and risk of non-Hodgkin lymphoma. J Natl Cancer Inst 2005;97:587–94.
(2) Ponsonby AL, van der Mei I, Dwyer T, Blizzard L, Taylor B, Kemp A, et al. Exposure to infant siblings during early life and risk of multiple sclerosis. JAMA 2005;293:463–9.
(3) Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 2001;1:69–75.[CrossRef][Medline]
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J Natl Cancer Inst 2005 97: 1475.
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