Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity.
BACKGROUND
Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.


METHODS
Using a case-control study design, breast cancer patients (n = 709) and appropriate age-matched and sex-matched controls obtained from the Breast Screening Unit (n = 498) were genotyped for these TNF polymorphisms, using a high-throughput allelic discrimination method.


RESULTS
Allele frequencies for both polymorphisms were similar in both breast cancer cases and controls. However, the -308 polymorphism was found to be associated with vascular invasion in breast tumours (P = 0.024). Comparison with other standard prognostic indices did not show any association for either genotype.


CONCLUSIONS
We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population. However, the -308 G>A polymorphism was found to be associated with the presence of vascular invasion in breast tumours.
Azmy
Iman A F
IA
Academic Surgical Oncology Unit, University of Sheffield, UK. i.azmy@doctors.net.uk
Balasubramanian
Saba P
SP
Wilson
Anthony G
AG
Stephenson
Timothy J
TJ
Cox
Angela
A
Brown
Nicola J
NJ
Reed
Malcolm W R
MW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha