Skin Cancer
Conditions
Keywords
single nucleotide polymorphisms, Toll-like receptor-4
Brief summary
Toll-like receptors (TLRs) play a key role in the innate immune system. Toll-like receptor-4 (TLR4) in particular, appears to play a role in susceptibility to cancer. Of 44 identified SNPs (small nucleotide polymorphisms) in TLR4, the most common is an A-G substitution at nucleotide position +896, downstream of the cDNA start codon, a missense mutation which leads to an amino acid substitution Asp299Gly in the third exon of the TLR4 gene. Pre-clinical studies from our laboratory have shown an association of TLR4 with ultraviolet radiation induced skin cancer. Hence, in this study we will assess the pattern of TLR4 polymorphisms and susceptibility to skin cancer.
Detailed description
Toll-like receptors (TLRs) play a key role in the innate immune system. Toll-like receptors generally, and TLR4 in particular, appear to play a role in cancer susceptibility as well as tumor immunosuppression and stromal invasion. Of 44 identified SNPs (small nucleotide polymorphisms) in TLR4, the most common is an A-G substitution at nucleotide position +896, downstream of the cDNA start codon, a missense mutation which leads to an amino acid substitution Asp299Gly in the third exon of the TLR4 gene, and which was later shown to co-segregate with SNP Thr399Ile-also in the third exon of TLR4.1 This SNP, present in 10% of the general population, has been found associated with gastric cancer, prostate cancer, and nasopharyngeal cancer.2-4 Pre-clinical studies from our laboratory have shown an association of TLR4 with ultraviolet radiation induced skin cancer. Hence, in this study we will assess the pattern of TLR4 polymorphisms and susceptibility to skin cancer.
Interventions
DIAGNOSTIC_TESTDetection of single nucleotide polymorphisms (SNP)
Asp299Gly SNP in the third exon of the TLR4 gene will be detected in blood
Sponsors
University of Alabama at Birmingham
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
50 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female over the age of 50 * Fitzpatrick skin type I-IV
Exclusion criteria
* Tumor types other than basal cell carcinoma, squamous cell carcinoma and melanoma * Chronic immunosuppression due to transplant antirejection regimen or HIV/AIDS * Nevoid basal cell carcinoma syndrome, Cowden's syndrome, xeroderma pigmentosum or other syndrome with skin-cancer predisposition * Known exposure to arsenic or ionizing radiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| single nucleotide polymorphism | once during the course of study | TLR4 SNP Asp299Gly |
Countries
United States
Outcome results
None listed