TLR4 Polymorphisms and Risk of Skin Cancer

NCT ID: NCT03122366

Last Updated: 2023-03-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 392 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-02-02
• Study Completion Date: 2011-09-27

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.

Conditions

Skin Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Interventions

Detection of single nucleotide polymorphisms (SNP)

Asp299Gly SNP in the third exon of the TLR4 gene will be detected in blood

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Nabiha Yusuf

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nabiha Yusuf

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

The Kirklin Clinic

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

F080815001

Identifier Type: -

Identifier Source: org_study_id