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 Blood, 5 November 2009, Vol. 114, No. 19, pp. 4014-4020.
Prepublished online as a Blood First Edition Paper on September 8, 2009; DOI 10.1182/blood-2009-03-209601.

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CLINICAL TRIALS AND OBSERVATIONS

A protective role for early oral exposures in the etiology of young adult Hodgkin lymphoma

Wendy Cozen1,2, Ann S. Hamilton1, Peng Zhao1, Muhammad T. Salam1, Dennis M. Deapen1, Bharat N. Nathwani2, Lawrence M. Weiss3, and Thomas M. Mack1,2

1 Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles; 2 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles; and 3 Department of Pathology, City of Hope National Medical Center, Duarte, CA

The pattern of adolescent/young adult Hodgkin lymphoma (YAHL) suggests causation by a relatively late infection with a common childhood virus, but no causal virus has been found. Susceptibility is heritable and linked to lower interleukin 12 (IL12) levels, which can also result from fewer fecal-oral microbial exposures early in life. We studied twin pairs discordant for YAHL to examine exposures capable of altering the IL12 response and T-helper type 1 (Th1)–Th2 balance. One hundred eighty-eight YAHL-discordant twin pairs from the International Twin Study returned questionnaires (70% response). Exposure history of YAHL case-twins was compared with that of their unaffected control-twins using conditional logistic regression for matched pairs to calculate odds ratios (ORs). Behaviors likely to produce oral exposure to microbes conveyed decreases in risk (univariable OR range = 0.2-0.5, P = .003-.11). Significant adjusted ORs were seen for appendectomy (OR = 4.3, P = .001), eczema (OR = 4.2, P = .025), smoking (OR = 2.2, P = .054), and relatively more frequent behaviors associated with oral exposures (OR = 0.1; P = .004). Kappa statistics for intrapair agreement were higher than 0.8 for each significant finding. Our observations support a protective role for increased early oral exposure to the microbiome, suggesting that factors associated with increased Th2 and decreased Th1 cytokines are etiologically relevant to YAHL.


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