Involvement of interleukin-10 promoter polymorphisms in nonmelanoma skin cancers-a case study in non-Caucasian skin cancer patients.
Interleukin 10 (IL-10) is a potent immunosuppressive cytokine, therefore elevated IL-10 expression has been implicated in inhibition of antitumor immune response. IL-10 gene promoter polymorphism has been shown to be involved in susceptibility to skin cancers, but there has been no report focusing on susceptibility to skin cancers among non-Caucasian populations. We enrolled 129 patients with skin cancers and 50 age- and sex-matched healthy controls between April 2004 and March 2007. Genomic DNA was extracted from patients' blood samples and IL-10 promoter polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism or direct sequencing. The distribution of the frequency of allele or haplotype of IL-10 gene promoter in Japanese was quite different from that of Europeans. No significant differences could be demonstrated in the frequency of allele or haplotype of IL-10 gene promoter between the patient group and the control group. However, the frequency of the low-IL-10 expression haplotype was significantly high in Bowen's disease subgroup. The frequency of low expression IL-10 promoter genotype was significantly less (P = 0.009, chi(2) = 6.74) in the group of nonmelanoma skin cancer generated on sun-exposed areas in comparison with that on covered areas. Our results indicated that low expression haplotype of IL-10 in Bowen's disease may inhibit the escape of tumor cells from immune surveillance, resulting in suppression of tumor growth and tumor invasion to the dermis. Moreover, high IL-10-expressing haplotype of IL-10 promoter may be a risk factor for photocarcinogenesis.
Nagano
Tohru
T
Division of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Kunisada
Makoto
M
Yu
Xijun
X
Masaki
Taro
T
Nishigori
Chikako
C
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007564:Japan; D008297:Male; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013472:Sunlight
D016753:Interleukin-10