PO-064 Early birth order and increased risk of lymphoid cancers and allergies in lymphoid cancer families

Abstract

Introduction Lymphoid cancers are a heterogeneous group of neoplasms that arise from immune cells. Familial clustering of lymphoid cancers support a genetic contribution to cancer predisposition. Infectious diseases and some immune disorders have been associated with lymphoid cancers. The hygiene hypothesis proposes that a lower infectious burden during early life inhibits the immune system from maturing optimally, and may lead to disorders of the immune system. Material and methods We characterised atopic conditions in lymphoid affected sibships of 182 families with a history of lymphoid cancers. Early life data was collected from telephone interviews and questionnaires from multiple family members. When available, medical records, pathology slides and tissue blocks were used to confirm the lymphoid cancer diagnosis. Lymphoid cancers were classified according to the InterLymph hierarchical classification (Turner, 2010). A chi-squared test for a linear trend in proportions was performed on birth order data for lymphoid affected sibships. This test was also performed on birth order and allergies in lymphoid affected sibships. Results and discussions Within 182 families, 301 sibships had 392 lymphoid affected and 927 unaffected siblings. We observed an inverse relationship between birth order and risk of cancer for all lymphoid cancers collectively (p<0.0001), and separately for multiple myeloma (p=0.0015), non-Hodgkin lymphoma (p<0.0001) and individual B-cell subtypes including chronic lymphocytic leukaemia (p=0.0124), follicular (p=0.0217) and marginal zone lymphoma (p=0.0169). We also observed an inverse relationship between birth order and risk of allergies (p=0.0284), for both environmental allergies (p=0.0465) and multiple allergies (p=0.0114) in lymphoid affected individuals. Conclusion Early life exposures that are dependent on birth order may play a role in immune dysregulation and subsequent risk of multiple types of lymphoid cancers, as well as allergies. The familial nature of the cancers implies shared genetic and/or environmental factors. There is a need for further evaluation of lifestyle factors that may protect against lymphoid cancers even in the familial context.