TLR4 Polymorphisms and Risk of Skin Cancer

TLR4 Polymorphisms and Predisposition for Skin Cancer Development

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.

Study Overview

• Status: Completed
• Conditions: Skin Cancer
• Intervention / Treatment: Diagnostic test: Detection of single nucleotide polymorphisms (SNP)

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.

• Study Type: Observational
• Enrollment (Actual): 392

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The Kirklin Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

400 patients age 50 and older (case group) will be enrolled at the time of presentation for skin cancer excision surgery. These patients will be stratified into melanoma and non-melanoma skin cancer subgroups, and the non-melanoma subgroup will be further divided into prior and no prior history of skin cancer. All groups will have blood drawn at the time of enrollment. 400 patients age 50 and older (control group) with no personal history of skin cancer will be enrolled at our clinical trials unit. These patients will be stratified into family history and no family history of skin cancer subgroups, and will have blood drawn at the time of enrollment.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
single nucleotide polymorphism	TLR4 SNP Asp299Gly	once during the course of study

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Nabiha Yusuf, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2009
• Primary Completion (Actual): September 27, 2011
• Study Completion (Actual): September 27, 2011

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: single nucleotide polymorphisms; Toll-like receptor-4
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Skin Neoplasms
• Other Study ID Numbers: F080815001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No