Abstract
Although cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is also increasing. cSCC has both a genetic and environmental etiology. Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10−42) within Hispanic/Latinos and with greater northern (P = 2.38 × 10−65) and western (P = 2.28 × 10−49) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.
Highlights
Cutaneous squamous cell carcinoma is one of the most common malignancies in individuals of European ancestry, the incidence of cutaneous squamous cell carcinoma (cSCC) in Hispanic/Latinos is increasing. cSCC has both a genetic and environmental etiology
We determine whether genetic ancestry associations are modified by sun exposure by considering actinic keratosis (AK) diagnosed by a physician as a clinical marker for chronic ultraviolet radiation (UVR) exposure and assessing whether observed genetic ancestry associations are comparable at sun-protected anatomical sites and with noncutaneous SCC
A greater risk of cSCC was associated with higher European ancestry among Hispanic/Latinos and northern and western European ancestry among non-Hispanic whites
Summary
Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is increasing. cSCC has both a genetic and environmental etiology. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10−42) within Hispanic/Latinos and with greater northern (P = 2.38 × 10−65) and western (P = 2.28 × 10−49) European ancestry within non-Hispanic whites These associations are significantly, but not completely, attenuated after considering skin pigmentationassociated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and nonHispanic whites, largely but not entirely mediated through its impact on skin pigmentation. We determine whether genetic ancestry associations are modified by sun exposure by considering actinic keratosis (AK) diagnosed by a physician as a clinical marker for chronic UVR exposure and assessing whether observed genetic ancestry associations are comparable at sun-protected anatomical sites and with noncutaneous SCC (ncSCC)
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