A role for infection and toll-like receptor gene variation in childhood acute lymphoblastic leukaemia

Download files
Access & Terms of Use
open access
Copyright: Beckett, Sara
Altmetric
Abstract
Acute lymphoblastic leukaemia (ALL) is the most common cancer in children, yet little is known about risk factors for the disease. Although previous research has suggested that the development of childhood ALL may be related to exposure to infections during early childhood, this has not yet been investigated in an Australian population. Initial recognition of pathogens as they enter the human body is determined in part by the Toll-like receptor (TLR) family. Polymorphisms in TLR genes have been associated with disease risk, implicating TLR gene variants as having a role in the aetiology of childhood ALL. The aim of this thesis was to investigate the association between evidence for early childhood exposures to infection, polymorphisms in TLR genes, and risk of childhood ALL in an Australian population. “The Australian study of causes of acute lymphoblastic leukaemia in children” (Aus-ALL) is a population-based case-control study of childhood ALL conducted in Australia between 2003 and 2007. Cases included children aged <15 years diagnosed with ALL while controls were recruited by random digit dialling from the general population. Information on immunisation history, birth order, daycare attendance, and breastfeeding as well as DNA samples were collected. Attending daycare (OR=0.69; 95% CI=0.48-0.98, p=0.04), and having one or more older siblings (OR=0.71, 95% CI=0.55-0.93, p=0.01) were found to be associated with a reduced risk of childhood ALL. Breastfeeding appeared to be protective (OR=0.55, 95% CI: 0.36 – 0.86, p=0.008). No difference in childhood immunisation history was detected between cases and controls (p>0.05). In females, the TLR4 rs4986790 variant allele (OR=0.46, 95% CI: 0.21 – 0.99, p=0.046), and TLR8 rs3764880 variant allele (OR=0.65, 95% CI: 0.43 – 0.99, p=0.047) were associated with a reduced risk of childhood ALL. The decreased risk associated with TLR4 rs4986790 and TLR8 rs3764880 variants was more evident for females born first compared to those born later. No significant associations were found between TLR polymorphisms and risk of childhood ALL in males. This thesis presents findings supporting an aetiological role for early childhood exposures to infection in childhood ALL and provides the first evidence of an association between TLR gene polymorphisms and risk of childhood ALL.
Persistent link to this record
Link to Publisher Version
Link to Open Access Version
Additional Link
Author(s)
Beckett, Sara
Supervisor(s)
Ashton, Lesley
Milne, Elizabeth
Creator(s)
Editor(s)
Translator(s)
Curator(s)
Designer(s)
Arranger(s)
Composer(s)
Recordist(s)
Conference Proceedings Editor(s)
Other Contributor(s)
Corporate/Industry Contributor(s)
Publication Year
2015
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
Files
download public version.pdf 1.32 MB Adobe Portable Document Format
Related dataset(s)