Transmission of HLA-DP variants from parents to children with B-cell precursor acute lymphoblastic leukemia: Log-linear analysis using the case-parent design

Malcolm Taylor, Tracy L. Bergemann, Adiba Hussain, Pamela D. Thompson, Logan Spector

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) is usually initiated in utero and is thought to progress to overt leukemia under the influence of delayed exposure to a common infection. Based on the hypothesis that polymorphic HLA-DP variants can restrict T-cell responses to infection, we previously compared DP supertype frequencies in BCP ALL patients with that of unrelated newborn controls. We reported that the DP2 supertype was associated with susceptibility, whereas DP1 was associated with protection. However, the association of genetic variants in children with early-onset diseases such as ALL may be a proxy for parental effects. Here we examine whether maternal DP1 and DP2 are associated with BCP ALL by fitting log-linear models in a combined series of family triads (both parents and case child) and dyads (1 parent and case child; n = 571) in comparison with similar models in non-BCP leukemia (n = 198). We report no evidence of maternal DP1 or DP2 associations with BCP ALL, but we did identify suggestive evidence of maternal undertransmission of the infrequent supertypes DP11 and DP15. Although these results require confirmation, they suggest that DP11 and DP15 may be protective or that there is transmission ratio distortion of these supertypes in BCP ALL.

Original languageEnglish (US)
Pages (from-to)897-903
Number of pages7
JournalHuman Immunology
Volume72
Issue number10
DOIs
StatePublished - Oct 2011

Bibliographical note

Funding Information:
This study was funded by grants from the Kay Kendall Leukaemia Fund (M Taylor). We are indebted to the children and families who took part in the UKCCS for enabling us to carry out this work. We thank Ms. J. Simpson and Professor E. Roman at the LRF Epidemiology and Genetics Unit, University of York, for providing diagnostic and other patient information. We are grateful to M. D. Robinson, Dr. C. Watson, Dr. D. A. Gokhale, and S. P. Dearden for sample processing and DPB1 typing. The UKCCS was sponsored and administered by the UK Coordinating Committee on Cancer Research and has been conducted by 12 teams of investigators (10 clinical and epidemiologic and 2 biologic) based in university departments, hospitals, research institutes, and the Scottish health service. The work is coordinated by a Management Committee and in Scotland by a Steering Group. It is supported by the UKCCS Group, consisting of pediatric oncologists, and by the National Radiological Protection Board. Funding has been provided by a consortium of statutory bodies, cancer charities, and industrial sponsors. A complete list of UKCCS investigators is given in UK Childhood Cancer Study Investigators, The United Kingdom Childhood Cancer Study: objectives, materials and methods (Br. J. Cancer 2000;82:1073–102).

Keywords

  • Childhood bcp ALL
  • HLA-DP supertype
  • Log-linear modeling
  • Maternal response
  • Parental transmission

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