INVESTIGATIVE REPORT
321
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Positive Association Between Vitamin D Serum Levels and Naevus Counts
Simone RIBERO 1 , 2 , Dan GLASS 1 , 3 , Massimo MANGINO 1 , Abraham AVIV 4 , Tim SPECTOR 1 and Veronique BATAILLE 1 , 5
1
Department of Twin Research & Genetic Epidemiology , King ’ s College London , St Thomas ’ campus , London , UK , 2 Department of Medical Sciences , Section of Dermatology , University of Turin , Italy , 3 Imperial College London , School of Medicine , London , UK , 4 Center of Human Development and Aging , Rutgers , The State University of New Jersey , New Jersey Medical School , Newark , USA , and 5 Department of Dermatology , West Herts NHS Trust , Herts , UK
Lower vitamin D serum levels are linked to increased melanoma risk and poorer survival . Naevus counts are associated with both melanoma risk and survival and to leucocyte telomere length . Vitamin D is also linked to telomere biology with higher levels of vitamin D in individuals with longer leucocyte telomere length despite adjusting for age . Using the TwinsUK data , we explored the association between naevus count , leucocyte telomere length and vitamin D serum levels . Increasing vitamin D levels were associated with increasing naevus count : serum levels were 73.3 nmol / l in individuals with less than 50 naevi compared to 78.8 nmol / l in individuals with more than 50 naevi ( p = 0.002 ). In the final regression model , using naevus count as a continuous variable , vitamin D remained associated with higher naevus counts despite adjustment for age , weight , height , season of sampling and twin relatedness ( p = 0.02 ). Further adjustment for leucocyte telomere length , decreased the magnitude of the association but it remained significant so leucocyte telomere length is not the sole driver of this association . Having large numbers of naevi is associated with higher vitamin D serum levels .
Key words : vitamin D ; melanoma ; naevus count ; 25 ( OH ) D . Accepted Nov 17 , 2016 ; Epub ahead of print Nov 21 , 2016 Acta Derm Venereol 2017 ; 97 : 321 – 324 .
Corr : Simone Ribero , MD , PhD , Department of Twin Research and Genetic Epidemiology , King ’ s College London , St Thomas ’ campus , Westminster Bridge Road , London , SE1 7EH , UK . E-mail : simone . ribero @ unito . it
Higher vitamin D ( 25 ( OH ) D ) levels have been shown to protect from melanoma and furthermore from melanoma recurrence ( 1 ). It is unclear whether 25 ( OH ) D serum levels are protective per se , or , are a proxy marker for other protective factors in melanoma ( 2 ). It is possible that higher 25 ( OH ) D is a reflection of healthier lifestyle which in turns confer some protection against cancer in general ( 3 ).
Twin studies have shown that naevus number is an heritable trait ( 4 ) and genome-wide association studies for melanoma and naevus counts have identified many SNPs explaining the genetic variation associated both with naevi number and melanoma risk ( 5 – 7 ). Naevus counts decrease with age . High naevus counts are also associated with longer leucocyte telomere length ( LTL ) despite adjusting for age which suggests that naevi number and size and senescence are linked ( 8 ).
Mounting evidence suggests that , in addition to its well described roles in skin , bone , and muscle physiology ( 9 ), 25 ( OH ) D acts as an inhibitor of the inflammatory response through several pathways . The inhibitory effect of vitamin D on the inflammatory response ( 10 ) also leads to a potential link between this vitamin and LTL biology ( 11 ), suggesting a potential role of 25 ( OH ) D in senescence ( 12 ). The relationship between vitamin D and melanoma is quite complex as many possible confounders may affect the significance of the association . It has been shown that both melanoma risk and melanoma recurrence may be increased in those with low vitamin D ( 13 – 15 ). The aim of this study was to look at the associations between number of naevi ( the strongest melanoma risk factor ) and 25 ( OH ) D serum levels .
METHODS
Ethics Committee approval for this study was obtained from the Guy ’ s and St Thomas Hospital NHS Trust , London . Subjects were not aware of the hypotheses being tested as they were part of a large study investigating many age-related diseases and traits for which informed written consent was obtained ( www . twinsuk . ac . uk ).
Three thousand five hundred and one consecutive women were recruited from the Twins UK Adult Twin Registry in London ( wwww . twinsuk . ac . uk ) between January 1995 and December 2003 . The twins involved in this study have previously been shown to be representative of the UK singleton population in general ( 16 ). All were adult females aged between 18 and 79 years of age .
Skin data
The validated protocol for naevus counts has previously been published elsewhere ( 17 ). In particular , a naevus was defined as a melanocytic lesion ≥ 2 mm in diameter to avoid any confusion with ephelides . Skin type was assessed according to the Fitzpatrick classification .
Vitamin D
Total 25 ( OH ) D levels were measured by radioimmunoassay using Diasorin RIA kit ( Diasorin , Minnesota , USA ) as previously described ( 10 ).
Leucocyte telomere length
DNA was extracted from isolated leukocytes after an overnight fast and the mean leukocyte terminal restriction fragment length
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2583 Acta Derm Venereol 2017 ; 97 : 321 – 324