Birth Order, Sibship Size, Childhood Environment and Immune-Related Disorders, and Risk of Lymphoma in Lymphoid Cancer Families

Abstract

Background: Familial aggregation of lymphoid cancers and immune-related disorders suggests a role for genetic susceptibility; however, few studies examine environmental factors. According to the hygiene hypothesis, adult-onset immune-related diseases may be a consequence of reduced childhood infectious exposures and aberrant immune development. In a cohort of 196 multiple-case lymphoid cancer families, we analyzed environmental factors related to the hygiene hypothesis.

Methods: Family structure, childhood environment, and immune-related disorders were examined among 196 lymphoid cancer families, in relation to risk of lymphoid cancer. We report on 450 lymphoid cancer cases and 1,018 unaffected siblings using logistic regression models with generalized estimating equations to estimate ORs and 95% confidence intervals (CI) for association.

Results: The risk of lymphoma tended to decrease with later birth order (OR = 0.83; 95% CI, 0.78-0.89) and larger sibship size (OR = 0.82; 95% CI, 0.79-0.85). High maternal education, above average family income during childhood, allergies (OR = 2.25; 95% CI, 1.44-3.51), and tonsillectomy (OR = 1.78; 95% CI, 1.14-2.78) were independent risk factors for lymphoma. Familial lymphoid cancer cases were more likely to report environment (OR = 1.90; 95% CI, 1.21-2.98) and drug (OR = 2.30; 95% CI, 1.41-3.73) allergies.

Conclusions: These associations underscore the complex etiology of familial lymphoma. To our knowledge, this is the largest multiple-case family-based study that supports the hygiene hypothesis contributing to lymphoid cancer risk.

Impact: Understanding the mechanism by which environmental and lifestyle factors affect lymphoid cancer risk may advance cancer prevention, even in the familial context.