LB34
Melanocytic naevus senescence: differential genetic influence on naevi with age
Daniel Glass1, Veronique Bataille1, Bernet Kato1, Massimo Mangino1, Mario Falchi1, Nicole Soranzo2, Panos Deloukas2, Nick Martin3, Tim Spector1, David Duffy3, Grant Montgomery3, Nick Hayward3
1King's College London, UK; 2Wellcome Trust Sanger Institute, Cambridge, UK; 3Queensland Institute of Medical Research, Brisbane, Australia
Background
Having large numbers of melanocytic naevi is the strongest risk factor for
melanoma. Recent genome wide association studies identified genes associated
with the development of melanocytic naevi. Naevi senesce, understanding the
genetics behind this senescence may lead to insight into melanoma biology.
Method
A genome wide association scan for melanocytic naevus count was undertaken
on 2200 Australian adolescent twins and their parents; to explore naevus
senescence using the Illumina 610K SNP array. Replication was on the same
platform in 1714 members of the Twins UK cohort, aged 18 79 to confirm age
related effects. The effect of naevus genes on melanoma risk was explored by a
further genome wide association within an Australian melanoma cohort.
Results
A gene on chromosome 6 is associated with higher naevus count in the
Australian adolescent twins (p=6 x 10-9); but associated with lower
naevus count in their parents. This age dependent effect was replicated in the
Twins UK cohort with young individuals homozygous for the risk allele having
significantly more naevi. Older individuals homozygous for the risk allele had
significantly fewer naevi (p<0.02). This gene was not associated with
melanoma risk within the Australian melanoma cohort.
Conclusion
We describe a gene on chromosome 6 associated with larger numbers of naevi
in youth but more rapid involution of melanocytic naevi with increasing age.
This gene may reflect the genetic influence on a particular naevus subtype with
high numbers of naevi with early senescence. These results help to unravel
genetic factors involved in melanocytic differentiation and may give further
clues towards the causation of melanoma as well as the relationship between
senescence and cancer.
References
[1]Falchi etal. Nature Genetics 41, 915 - 919 (2009)
