Foxp3 promoter polymorphism (rs3761548) in breast cancer progression: a study from India

Abstract

Breast cancer is the most common female neoplasm that drives the transformation of normal mammary epithelial cells into highly malignant derivatives. Forkhead Box Protein3 (Foxp3), a tumor suppressor/immunomodulatory gene, which controls the function of Treg cells and oncogenes is down regulated in breast cancer. The main aim of the present study is to evaluate the potential influence of Foxp3-3279 C>A polymorphism (rs3761548) and -2383 C>T polymorphism (rs3761549) in 202 breast cancer patients and 130 normal healthy women of Indian origin. The genotypes were determined using ARMS-PCR for rs3761548 and PCR-RFLP method for rs3761549 using specific primers. The results revealed lack of association of these two polymorphisms with breast cancer susceptibility. However, with respect to AA genotype of rs3761548, we found highly significant association with the advanced stage (T3-4) of the tumor (OR = 3.90; 95% confidence interval (CI) = 1.56-9.70; p = 0.03). Stratified data also revealed an association of homozygous mutant genotype with advanced stage of tumor in premenopausal women (OR = 4.56; 95% CI = 1.07-19.38; p = 0.04) with disease duration of <6 months (OR = .10; 95% CI = 1.80-20.50; p = 0.002) suggestive of modulating effect of rs3761548 in tumor progression. We conclude that Foxp3 rs37161548 has a potential to be a polymorphic marker for tumor progression in premenopausal breast cancer patients in Indian women.

Association of FoxP3 rs3761548 polymorphism with susceptibility to colorectal cancer in the Chinese population

“…The association between the FOXP3 polymorphism and various cancers has been reported as well for breast cancer [15,16] and hepatocellular carcinoma [17] but this polymorphism has not been reported to confer susceptibility to CRC in a Chinese Han population. Ours is the first to show that a FoxP3 gene polymorphism confers CRC risk and that the AA, AC, and combined A variant genotypes (AA?AC) significantly increased susceptibility to CRC.…”

“…FOXP3 gene polymorphisms may change Foxp3 functionally or quantitatively, decreasing or eliminating functional Tregs. Also, the FOXP3 polymorphism is associated with autoimmune disease such as allergic rhinitis [12], Graves' disease [13], and psoriasis [14], as well as breast cancer [15,16] and hepatocellular carcinoma [17]. The role of the FOXP3 rs3761548 polymorphism in CRC susceptibility in a Chinese Han population is not certain, so we investigated the association between the FOXP3 rs3761548 polymorphism and the risk of CRC.…”

Association between FOXP3, FOXE1 Gene Polymorphisms and Risk of Differentiated Thyroid Cancer in Chinese Han Population

“…These all suggested that a strong activation of oncogenic processes would exist in this lesion. The Foxp3-rs3761548 polymorphisms had been reported to be associated with the risk of various cancers [25,26]. In addition, the Foxp3 gene polymorphisms at rs2280883 and rs3761549 sites may be associated with hepatitis B-related hepatocellular carcinoma [27].…”

Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis

“…A considerable number of published studies have associated this polymorphism with diseases and other conditions that reflect Treg deficiency, such as allergic rhinitis (325), susceptibility to vitiligo (326), psoriasis (327), some autoimmune diseases (328), non-small-cell lung cancer (329), and breast cancer (330). This association has not been confirmed for other disorders, including endometriosis-associated infertility (319) and systemic sclerosis (331).…”