Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-25T14:12:08.159Z Has data issue: false hasContentIssue false

Linkage and Association Analysis of Radiation Damage Repair Genes XRCC3 and XRCC5 with Nevus Density in Adolescent Twins

Published online by Cambridge University Press:  21 February 2012

Gu Zhu
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
David L. Duffy
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
David R. Turner
Affiliation:
Department of Haematology and Genetic Pathology, School of Medicine, Flinders University of South Australia,Adelaide, Australia.
Kelly R. Ewen
Affiliation:
Australian Genome Research Facility, Melbourne, Australia.
Grant W. Montgomery
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
Nicholas G. Martin*
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia. [email protected]
*
*Address for correspondence: Dr N.G. Martin, Queensland Institute of Medical Research, Brisbane QLD 4029, Australia.

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

Type
Articles
Copyright
Copyright © Cambridge University Press 2003