Genetic variant in CXCL12 gene raises susceptibility to HPV infection and squamous intraepithelial lesions development: a case-control study.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted virus in women worldwide. The persistence of the virus may cause warts that are considered benign lesions and low or high grade intraepithelial lesions (LSIL/HSIL). Immunological system plays an important role in the resolution of infections. In this context, we highlight the chemokines, which are important regulators in the development of viral infections and inflammation. Among which CXCL12 stands out, due to its pro-inflammatory features, acting as chemoattractant recruiting immune cells. Several polymorphisms were identified in CXCL12 gene including rs1801157 in the 3'-untranslated region, which is characterized by a substitution of a guanine for an adenine. METHODS: In this study, 195 women were classified as HPV non-infected and 169 as HPV-infected. HPV-DNA was detected by polymerase chain reaction (PCR) and the polymorphism was assessed in blood cells through restriction fragment length polymorphism analysis. RESULTS: HPV infection was more incident in women who had more than 4 sexual partners during lifetime (p = 0.007), among those who presented lower number of pregnancies (p = 0.017). HPV was more prevalent among allele A carriers confirmed by logistic regression analysis adjusted for several confounding factors [ORADJ = 4.985; CI95% (2.85-8.72), p < 0.001]. An association between allele A carriers and HSIL development (p = 0.003) was also observed. CONCLUSIONS: In the present study, we demonstrated that CXCL12 rs1801157 is independently associated with HPV infection and exerts influence in HSIL development, suggesting it as a promising susceptibility biomarker for HPV infection and lesions development.

Screening of circulating TGF-ß levels and its clinicopathological significance in human breast cancer.

BACKGROUND: Transforming growth factor beta-1 (TGF-ß1) participation in breast cancer development and metastasis is well-established, however, the clinical meaning of its circulating levels in women with breast cancer is poorly understood. AIM: To characterize the levels of TGF-ß1 in plasma from women with breast cancer and to associate them with the main clinical factors associated with disease prognosis. PATIENTS AND METHODS: TGF-ß1 levels were measured by Enzyme-linked immunoassay (ELISA). Clinicopathological data were also assessed. RESULTS: Women bearing triple-negative tumors presented significantly reduced levels of this cytokine when compared to the other subtypes (p=0.0338). Patients with metastases exhibited lower levels of TGF-ß1 than the non-metastatic cohort (p=0.0442). Patients with early-onset disease had the highest plasma TGF-ß1 levels (p=0.0036). Doxorubicin chemotherapy induced a reduction in TGF-ß1 level, promptly after drug infusion (p=0.0494). Patients with TGF-ß1 levels lower than 20 pg/ml exhibited a tendency to have a reduced overall survival in a 40-month follow-up. CONCLUSION: Lower levels of circulating TGF-ß1 are associated with a poor disease prognosis.