There's three studies on skin pigmentation and cancer in the latest Nature Genetics, and a commentary piece (see below) synthesizing the findings. One study is a whole genome association study for skin cancer, finding two SNPs on chromosome 20. Another is a candidate gene study looking at the association of variants in TYR and ASIP on skin cancer risk. Finally, another study finds an association of "new" variants in ASIP and TPCN2 with pigmentation among Icelanders and Dutch individuals. I think that the most interesting, but not necessarily surprising, thing here is how the associations with skin cancer risk differ between populations.
Nature Genetics 40, 817 - 818 (2008)
Abstract: Pigmentation traits are known risk factors for skin cancer. Now, three new studies provide insights into the genetic factors underlying these effects, and the results reveal a surprisingly complex picture of the relationship between pigmentation traits and disease risk.
ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma
Daniel F Gudbjartsson, Patrick Sulem et al.
Nature Genetics 40, 886 - 891 (2008)
Abstract: Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 10-9) and BCC (OR = 1.33, P = 1.2 10-6). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 10-7) and BCC (OR = 1.14, P = 6.1 10-4). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 10-4). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.Common sequence variants on 20q11.22 confer melanoma susceptibility
Kevin M Brown, et al.
Nature Genetics 40, 838 - 840 (2008)
Abstract: We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P less than 1 10-15). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.Two newly identified genetic determinants of pigmentation in Europeans
Patrick Sulem, et al.
Nature Genetics 40, 835 - 837 (2008)
Abstract: We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R.
1 comment:
This is very useful post about the Genetic role in skin pigmentaion and cancer problems. Althouhg some experts say that the autoimmunity is more involve in the pigmentation disease. But deep study like on this post shows that genes are the basic and factor causing such disease.
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