Polymorphism in codons 10 and 25 of the transforming growth factor-beta 1 (TGF-beta1) gene in patients with invasive squamous cell carcinoma of the uterine cervix.

Transforming growth factor-beta 1 (TGF-beta1) has a multifactorial role in the development of cervical cancer. It potently inhibits the growth of epithelial cells that harbour oncogenic human papilloma viruses (HPVs). TGF-beta1 also inhibits the expression of the early viral transforming regions E6 and E7, which appear to be the key oncoproteins. It has been suggested that squamous cell carcinomas are devoid of TGF-beta1, raising the possibility that elevated levels of this growth factor could protect against cervical cancer. It is also recognized that the production and levels of TGF-beta1 are genetically predetermined and individually variable. Two genetic polymorphisms in the DNA encoding the leader sequence of the TGF-beta1 gene have been described and shown to be associated with the production of high or low TGF-beta1 levels in vivo and in vitro. We hypothesized that the inheritance of these polymorphisms could influence the development of invasive cervical cancer. This hypothesis was investigated by studying polymorphism in codons 10 and 25 of the TGF-beta1 gene. We studied 97 patients with invasive cervical cancer and 73 healthy controls and found that the distributions of alleles T (Leu) and/or C (Pro) and alleles G (Arg) and/or C (Pro) in codons 10 and 25, respectively, were similar. There was no significant association between the alleles and the histological degree of cancer differentiation. It appears that the role of this growth factor in cervical oncogenesis is not related to the point mutations that we examined in codons 10 and 25 of the TGF-beta1 gene. We speculate that other factors, including additional polymorphisms of the TGF-beta1 gene, the status of TGF-beta1 receptors, the complex cytokine network, differential responsiveness of cells to the stimuli, and the status of the precancer/cancer genome, may play a role in development of invasive cervical cancer.