A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus

Jiali Han, Abrar A. Qureshi, Hongmei Nan, Jiangwen Zhang, Yiqing Song, Qun Guo, David J. Hunter

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Genome-wide association studies on pigmentary phenotypes provide a pool of candidate genetic markers for skin cancer risk. The SNPs identified from a genome-wide association study of natural hair color were assessed for associations with the risk of three types of skin cancer simultaneously in a nested case-control study within the Nurses' Health Study [218 melanoma, 285 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) cases, and 870 common controls]. Along with two known pigmentation loci, MC1R and OCA2, the IRF4 rs12203592 T allele was associated with an increased risk of each type of skin cancer (P value, 6.6 × 10-4 for melanoma, 7.0 × 10-7 for SCC, and 0.04 for BCC). This association was further replicated in additional samples (190 melanoma, 252 SCC, and 634 common controls). The P value in the replication set was 0.03 for melanoma and 4.2 × 10-3 for SCC. The risk of BCC was replicated in an independent set of 213 cases and 718 controls (P value, 0.02). The combined results showed that the association with SCC reached the genome-wide significance level [odds ratio (OR) for additive model=1.61, 95%CI, 1.36-1.91, P=3.2×10-8]. The OR was 1.49 for melanoma (95%CI, 1.23-1.80; P = 4.5 × 10-5), and 1.32 for BCC (95%CI, 1.11-1.57; P = 1.6×10-3). Given that the T allele was shown previously to be associated with increased expression of IRF4 locus, further studies are warranted to elucidate the role of the IRF4 gene in human pigmentation and skin cancer development.

Original languageEnglish (US)
Pages (from-to)1533-1539
Number of pages7
JournalCancer Research
Volume71
Issue number5
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Skin Neoplasms
Basal Cell Carcinoma
Squamous Cell Carcinoma
Melanoma
Genes
Genome-Wide Association Study
Pigmentation
Alleles
Odds Ratio
Hair Color
Genetic Markers
Single Nucleotide Polymorphism
Case-Control Studies
Nurses
interferon regulatory factor-4
Genome
Phenotype
Health

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus. / Han, Jiali; Qureshi, Abrar A.; Nan, Hongmei; Zhang, Jiangwen; Song, Yiqing; Guo, Qun; Hunter, David J.

In: Cancer Research, Vol. 71, No. 5, 01.03.2011, p. 1533-1539.

Research output: Contribution to journalArticle

Han, Jiali ; Qureshi, Abrar A. ; Nan, Hongmei ; Zhang, Jiangwen ; Song, Yiqing ; Guo, Qun ; Hunter, David J. / A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus. In: Cancer Research. 2011 ; Vol. 71, No. 5. pp. 1533-1539.
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abstract = "Genome-wide association studies on pigmentary phenotypes provide a pool of candidate genetic markers for skin cancer risk. The SNPs identified from a genome-wide association study of natural hair color were assessed for associations with the risk of three types of skin cancer simultaneously in a nested case-control study within the Nurses' Health Study [218 melanoma, 285 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) cases, and 870 common controls]. Along with two known pigmentation loci, MC1R and OCA2, the IRF4 rs12203592 T allele was associated with an increased risk of each type of skin cancer (P value, 6.6 × 10-4 for melanoma, 7.0 × 10-7 for SCC, and 0.04 for BCC). This association was further replicated in additional samples (190 melanoma, 252 SCC, and 634 common controls). The P value in the replication set was 0.03 for melanoma and 4.2 × 10-3 for SCC. The risk of BCC was replicated in an independent set of 213 cases and 718 controls (P value, 0.02). The combined results showed that the association with SCC reached the genome-wide significance level [odds ratio (OR) for additive model=1.61, 95{\%}CI, 1.36-1.91, P=3.2×10-8]. The OR was 1.49 for melanoma (95{\%}CI, 1.23-1.80; P = 4.5 × 10-5), and 1.32 for BCC (95{\%}CI, 1.11-1.57; P = 1.6×10-3). Given that the T allele was shown previously to be associated with increased expression of IRF4 locus, further studies are warranted to elucidate the role of the IRF4 gene in human pigmentation and skin cancer development.",
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