Haplotypes in the tumour necrosis factor region and myeloma.
This study described the haplotypic structure across a region of chromosome 6 including the tumour necrosis factor (TNF) gene, and investigated its influence on the aetiology of myeloma. A total of 181 myeloma cases from the Medical Research Council Myeloma VII trial and 233 controls from the Leukaemia Research Fund Case Control Study of Adult Acute Leukaemia were included in the analysis. Genotyping by induced heteroduplex generator analysis was carried out for single nucleotide polymorphisms (SNP) located at positions -1031, -863, -857, -308 and -238 of the 5' promoter region of TNF-alpha gene, and 252 in the LT-alpha gene; and five microsatellites, TNFa, b, c, d and e. Haplotypes were inferred statistically using the phase algorithm. A limited diversity of haplotypes was observed, with the majority of variation described by 12 frequent haplotypes. Detailed characterization of the haplotype did not provide greater determination of disease risk beyond that described by the TNF-alpha-308 SNP. Some evidence was provided for a decreased risk of myeloma associated with the TNF-alpha-308 variant allele A, odds ratio, 0.57; 95% confidence interval, 0.38-0.86. The results of this study did not support our starting hypothesis; that high producer haplotypes at the TNF locus are associated with an increased risk of developing myeloma.
Morgan
Gareth J
GJ
Section of Haemato-Oncology, Institute for Cancer Research, Royal Marsden Hospital, London, UK. gareth.morgan@rmh.nhs.uk
Adamson
Peter J
PJ
Mensah
Fiona K
FK
Spink
Charlotte F
CF
Law
Graham R
GR
Keen
Leigh J
LJ
Roman
Eve
E
Davies
Faith E
FE
Rollinson
Sara
S
Child
J A
JA
Bidwell
Jeffrey L
JL
D000328:Adult; D002896:Chromosomes, Human, Pair 6; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D048069:Tumor Necrosis Factors / Q000235:genetics*
D048069:Tumor Necrosis Factors