engleski

TNF alpha genotypes in benign and malignant breast lesions

Etiology of breast cancer is extremely complex and not completely elucidated. It involves numerous genetic, endocrine, and external environmental factors. Connection between inflammatory processes and cancer has been suggested more than century ago, in 1863 by Virchow. Over the past ten years many studies supported the hypothesis that inflammatory mediators may have impact on cancer development and progression, including breast cancer. Links between cancer and inflammation are starting to have implications on prevention and treatment of malignant diseases. Tumor necrosis factor alpha (TNF alpha) is a multifunctional cytokine that plays an important role in the pathogenesis of inflammatory, autoimmune and malignant diseases. It has large spectrum of activities, including both antitumorigenic and protumorigenic. Blood levels of TNF alpha are significantly higher in patients with solid tumors. Recently, several TNF alpha promoter polymorphisms have been identified and related to the expression level of this cytokine and to the susceptibility to solid tumors, including breast cancer. The aim of our study was to investigate the frequency and role of three TNF alpha promoter polymorphisms (-1031, -308 and -238) in benign (fibrocystic changes) and malignant (invasive carcinoma) breast lesions. These polymorphisms were determined in 51 patients with benign and 82 patients with malignant breast lesions. The “ real-time” PCR SNP analysis was used. The high expression genotypes at any of the three SNP polymorphisms were more frequent in invasive breast carcinoma (in 35 of 82 examined, 42.9%) than in fibrocystic changes (in 17 of 51 examined, 33.3%). Samples with two high expression genotypes were more frequent in invasive breast carcinoma than in samples with fibrocystic changes. The combined frequency of high production genotypes (-1031 T/C and C/C, -308 G/A and A/A and -238 G/A and A/A) was more frequent in patients with invasive breast carcinoma than in fibrocystic changes. Our results suggest the difference between TNF alpha genotypes between fibrocystic changes and invasive breast carcinoma. Studying similarities and differences between benign and malignant breast lesions including the potential differences in cytokines polymorphisms may improve our understanding of malignant phenotype.

TNFalpha; breast cancer; SNP

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