Influence of TNFalpha and LTalpha single nucleotide polymorphisms on susceptibility to and prognosis in cutaneous malignant melanoma in the British population
Influence of TNFalpha and LTalpha single nucleotide polymorphisms on susceptibility to and prognosis in cutaneous malignant melanoma in the British population
Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that increased expression of tumour necrosis factor (TNF) ?, upregulated by UV exposure, may contribute to tumour escape from the immune response. In this study, we addressed whether single nucleotide polymorphisms (SNPs) in the TNF? promoter and lymphotoxin (LT) ? gene are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, and tumour regression) in CMM. One hundred and forty-six British Caucasian CMM patients and 220 controls were typed for TNF??376, ?308 and ?238 and LT? +252 SNPs by ARMS-PCR. Only the TNF??238 GG (P = 0.05) and GA (P = 0.03) genotypes showed slight, but significant, associations with CMM, while LT? +252 AA was associated with a higher mitotic count in vertical growth phase tumours (P = 0.02). Both TNF??238 and LT? +252 SNPs showed linkage disequilibrium with HLA-DQB1*0303 and *0301 alleles, variably implicated in CMM susceptibility/prognosis. In addition, TNF??238, ?308, LT? +252 haplotypes were assigned and compared. The GGA haplotype showed a modest association with CMM (P = 0.04) and with stage of disease (P = 0.03) and initial growth phase in CMM (P = 0.02), but these associations were only significant when P-values were uncorrected. Unlike basal cell carcinoma, these preliminary findings suggest that genetic variation associated with differential TNF? and LT? production is unlikely to play a major, independent role in susceptibility to, and perhaps prognosis in, CMM.
17-23
Howell, W. M.
dc6fe896-2230-4cf3-9862-f979cb872454
Turner, S.J.
71b4c3b4-1619-410d-a57a-85bcdbfd3f39
Collins, A.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Bateman, A.C.
4e97a5ca-662c-451d-bdb3-33f35420ceed
Theaker, J.M.
e24ec934-c79c-471c-8556-d38a15ac845b
12 February 2002
Howell, W. M.
dc6fe896-2230-4cf3-9862-f979cb872454
Turner, S.J.
71b4c3b4-1619-410d-a57a-85bcdbfd3f39
Collins, A.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Bateman, A.C.
4e97a5ca-662c-451d-bdb3-33f35420ceed
Theaker, J.M.
e24ec934-c79c-471c-8556-d38a15ac845b
Howell, W. M., Turner, S.J., Collins, A., Bateman, A.C. and Theaker, J.M.
(2002)
Influence of TNFalpha and LTalpha single nucleotide polymorphisms on susceptibility to and prognosis in cutaneous malignant melanoma in the British population.
European Journal of Immunogenetics, 29 (1), .
(doi:10.1046/j.1365-2370.2002.00269.x).
Abstract
Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that increased expression of tumour necrosis factor (TNF) ?, upregulated by UV exposure, may contribute to tumour escape from the immune response. In this study, we addressed whether single nucleotide polymorphisms (SNPs) in the TNF? promoter and lymphotoxin (LT) ? gene are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, and tumour regression) in CMM. One hundred and forty-six British Caucasian CMM patients and 220 controls were typed for TNF??376, ?308 and ?238 and LT? +252 SNPs by ARMS-PCR. Only the TNF??238 GG (P = 0.05) and GA (P = 0.03) genotypes showed slight, but significant, associations with CMM, while LT? +252 AA was associated with a higher mitotic count in vertical growth phase tumours (P = 0.02). Both TNF??238 and LT? +252 SNPs showed linkage disequilibrium with HLA-DQB1*0303 and *0301 alleles, variably implicated in CMM susceptibility/prognosis. In addition, TNF??238, ?308, LT? +252 haplotypes were assigned and compared. The GGA haplotype showed a modest association with CMM (P = 0.04) and with stage of disease (P = 0.03) and initial growth phase in CMM (P = 0.02), but these associations were only significant when P-values were uncorrected. Unlike basal cell carcinoma, these preliminary findings suggest that genetic variation associated with differential TNF? and LT? production is unlikely to play a major, independent role in susceptibility to, and perhaps prognosis in, CMM.
This record has no associated files available for download.
More information
Published date: 12 February 2002
Additional Information:
This work was supported by a grant from the Association for International Cancer Research, St Andrews, UK (No. 99-121).
Identifiers
Local EPrints ID: 24771
URI: http://eprints.soton.ac.uk/id/eprint/24771
ISSN: 0960-7420
PURE UUID: 5fbd40ba-6249-4ec2-8c90-e1e5e0378888
Catalogue record
Date deposited: 04 Apr 2006
Last modified: 16 Mar 2024 02:42
Export record
Altmetrics
Contributors
Author:
W. M. Howell
Author:
S.J. Turner
Author:
A.C. Bateman
Author:
J.M. Theaker
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics