TY - JOUR
T1 - Body site-specific genetic effects influence naevus count distribution in women
AU - Visconti, Alessia
AU - Ribero, Simone
AU - Sanna, Marianna
AU - Spector, Timothy D
AU - Bataille, Veronique
AU - Falchi, Mario
N1 - This article is protected by copyright. All rights reserved.
PY - 2019/8/12
Y1 - 2019/8/12
N2 - Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (P=8.5x10-5 ), showing that a high naevus count on this site persists from childhood throughout life. Then, using data from 3,232 twins, we observed, in women, the lowest naevus count heritability on the trunk (26%), and the highest on the lower limbs (69%). Finally, we showed that, in 2,864 women, six genomic loci previously associated with both naevus count and melanoma risk (IRF4, DOCK8, MTAP, 9q31.2, KITLG, and PLA2G6) have an effect on naevus count that is body site-specific, but whose effect sizes are predominantly stronger on the lower limbs. Sex-specific genetic influence on naevus count at different sites may explain differences in site-specific melanoma incidence as well as prognosis between sexes. This article is protected by copyright. All rights reserved.
AB - Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (P=8.5x10-5 ), showing that a high naevus count on this site persists from childhood throughout life. Then, using data from 3,232 twins, we observed, in women, the lowest naevus count heritability on the trunk (26%), and the highest on the lower limbs (69%). Finally, we showed that, in 2,864 women, six genomic loci previously associated with both naevus count and melanoma risk (IRF4, DOCK8, MTAP, 9q31.2, KITLG, and PLA2G6) have an effect on naevus count that is body site-specific, but whose effect sizes are predominantly stronger on the lower limbs. Sex-specific genetic influence on naevus count at different sites may explain differences in site-specific melanoma incidence as well as prognosis between sexes. This article is protected by copyright. All rights reserved.
KW - Candidate Gene Association Study
KW - heredity
KW - lower extremity
KW - melanoma
KW - naevus
UR - http://www.scopus.com/inward/record.url?scp=85071045125&partnerID=8YFLogxK
U2 - 10.1111/pcmr.12820
DO - 10.1111/pcmr.12820
M3 - Article
C2 - 31403758
SN - 1755-1471
JO - Pigment cell & melanoma research
JF - Pigment cell & melanoma research
ER -