Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA.
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
J Invest Dermatol. 2018 Mar;138(3):557-561. doi: 10.1016/j.jid.2017.09.034. Epub 2017 Oct 17.
Genome-wide association studies have identified genetic loci associated with cutaneous squamous cell carcinoma (cSCC) risk, but single-nucleotide polymorphism associations with cSCC invasiveness have not been investigated. We examined associations between cSCC invasiveness and 23 reported single-nucleotide polymorphisms among 67,833 non-Hispanic white subjects. Additionally, we performed a genome-wide scan and identified one SNP with significantly different frequencies in 5,724 subjects with at least one invasive tumor and 1,943 subjects with in situ tumors only. We then compared genotype frequencies among the invasive and in situ groups with those of 60,166 control subjects. The genome-wide scan identified that the T allele in single-nucleotide polymorphism rs41269979 in the class II human leukocyte antigen region was more frequent in the invasive than the in situ group (P = 4.93 × 10). Single-nucleotide polymorphisms in five of the 23 previously associated loci showed odds ratio heterogeneity between the in situ and invasive groups: rs447510 in HLA-DQA1 (P = 2.93 × 10), rs12203592 in IRF4 (P = 3.94 × 10), rs1805007 in MC1R (P = 7.71 × 10), and two SNPs in DEF8 (rs4268748, P = 1.09 × 10 and rs8063761, P = 1.40 × 10). These findings may provide new insight into the genetic basis of cSCC invasiveness and may help identify individuals at higher risk for developing clinically aggressive cSCC.
全基因组关联研究已经确定了与皮肤鳞状细胞癌 (cSCC) 风险相关的遗传位点，但尚未研究单核苷酸多态性与 cSCC 侵袭性的关系。我们检查了 67833 名非西班牙裔白人受试者中 23 个已报道的单核苷酸多态性与 cSCC 侵袭性之间的关联。此外，我们进行了全基因组扫描，在至少有一个侵袭性肿瘤的 5724 名受试者和仅有原位肿瘤的 1943 名受试者中发现了一个 SNP 频率有显著差异。然后，我们将侵袭性和原位组的基因型频率与 60166 名对照受试者的进行了比较。全基因组扫描发现，位于 II 类人白细胞抗原区域的单核苷酸多态性 rs41269979 中的 T 等位基因在侵袭性组中比在原位组中更为常见 (P = 4.93×10)。在 23 个先前与 rs447510 相关的位点中，有 5 个单核苷酸多态性在原位和侵袭性组之间显示出比值比异质性：HLA-DQA1 中的 rs12203592 (P = 2.93×10)、IRF4 中的 rs1805007 (P = 3.94×10)、MC1R 中的 rs1805007 (P = 7.71×10)，以及 DEF8 中的两个 SNPs(rs4268748，P = 1.09×10 和 rs8063761，P = 1.40×10)。这些发现可能为 cSCC 侵袭性的遗传基础提供新的见解，并可能有助于识别出患有侵袭性 cSCC 的风险较高的个体。
