Association between polymorphisms in TP53 and XRCC1 genes and the high-risk HPV and tumor markers in women with cervical cancer

Цель - оценить ассоциацию генов TР53 (rs1042522) и XRCC1 (rs25487, rs1799782) со статусом по вирусу папилломы человека (ВПЧ) и уровнем онкомаркеров у женщин киргизской национальности с раком шейки матки (РШМ). Материалы и методы. Исследование проведено по типу «случай-контроль» и включало 103 женщин с гистологически верифицированным диагнозом РШМ и 102 женщин без онкологической патологии в анамнезе. Генотипирование пациентов осуществлялось методом ПЦР-ПДРФ. Проведено типировование ВПЧ 16 и 18 типов, в сыворотке крови определены уровни ракового эмбрионального антигена (РЭА) и SCC (squamous cell carcinoma antigen). Результаты. Генотипы Pro/Pro и Arg/Pro полиморфизма p.Arg72Pro гена ТР53 были ассоциированы с наличием у женщин с РШМ ВПЧ 16 типа - ОШ=1,98 (95% ДИ=1,01-3,86, p=0,04), а генотип Pro/Pro полиморфизма p.Arg72Pro гена ТР53 - с ВПЧ 18 типа - ОШ=9,15 (95% ДИ=1,78-46,96, p=0,002). Высокие уровни онкомаркеров РЭА и SCC чаще встречаются у пациентов с РШМ, имеющих размер первичного опухолевого узла более 4 см. Патологически высокие уровни РЭА и SCC ассоциированы преимущественно с ВПЧ 16 типа. Заключение. Наличие аллеля Pro (генотипов Pro/Pro и Pro/Arg) по ОНП p.Arg72Pro (ген ТР53) у женщин с РШМ ассоциировано с положительным статусом по высокоонкогенным ВПЧ 16 и 18 типов. Aim: Evaluation of the role of TР53 (rs1042522), XRCC1 (rs25487, rs1799782) gene depending on the human papillomavirus (HPV), morphological parameters of the tumor and tumor markers of the blood among women with cervical cancer (CC) in Kyrgyz Republic. Methods. This was a case-control study of 205 women of Kyrgyz origin with morphologically verified CC (N=103) and 102 women without cancer and chronic diseases. Genotyping was performed by PCR-RFLP method. HPV 16 and 18 types, levels of squamous cell carcinoma (SCC) and сarcinoembryonic antigen (CEA) tumor markers were detected. Results. A relationship has been identified between the genetic and clinical and biochemical parameters: Pro/Pro и Arg/Pro for single-nucleotide polymorphism p.Arg72Pro of the ТР53 gene were associated with HPV 16 type - OR 1,98 (95% CI=[1,01-3,86]), p=0,04; Pro/Pro for p.Arg72Pro of the ТР53 - with HPV 18 type - OR =9,15 (95% CI=[1,78-46,96]), p=0,002. Among patients with tumor size of more than 4 cm are more common high levels of CEA and SCC tumor markers. High levels of CEA and SCC are associated mainly with type 16 HPV. Conclusions. The results of the present study suggest that the presence of the Pro allele (genotypes Pro/Pro and Pro/Arg) by SNP p.Arg72Pro (TP53 gene) among women with cervical cancer is associated with a positive status for highly oncogenic HPV 16 and 18 types.

Download Full-text

Expression of immune cell markers and tumor markers in patients with cervical cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001254 ◽

2020 ◽

Vol 30 (7) ◽

pp. 969-974

Author(s):

Liming Zhang ◽

Hui Zhang ◽

Yuheng Huang ◽

Xiaowei Xi ◽

Yunyan Sun

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Carcinoembryonic Antigen ◽

Tumor Markers ◽

Squamous Cell ◽

Early Stage ◽

Locally Advanced ◽

Control Group ◽

Healthy Women

ObjectiveCervical cancer is one of the most common cancers worldwide, and immune function may impact disease progression. Serum markers may also be associated with diagnosis and progression. The aim of this study was to explore the clinical usefulness of determining the levels of peripheral blood immune cells and serum tumor markers in predicting diagnosis and prognosis of patients with cervical cancer.Methods82 patients with cervical cancer (early stage group: IA–IB1 and IIA1; locally advanced group: IB2 and IIA2), 54 patients with cervical intra-epithelial neoplasia (CIN), and 54 healthy women (control group) were recruited. Inclusion criteria were: (1) patients whose cervical lesions were determined based on biopsy; and (2) patients who had not undergone immunotherapy, chemotherapy, or radiotherapy. The exclusion criteria were as follows: (1) patients with a history of other malignant tumors; (2) patients with heart, kidney, and other organ failure; (3) patients with immune diseases; and (4) pregnant or lactating women. The levels of immunocytes and tumor markers were assayed. The relationships among histopathologic factors were analyzed. The correlation between the levels of immunocytes and tumor markers in patients with different degrees of cervical lesions (pre-invasive or cancer) and healthy women was evaluated.ResultsThe squamous cell carcinoma antigen and carcinoembryonic antigen levels in the control group and the CIN group were significantly lower than those in the cervical cancer groups (p<0.01). The incidence of lymph node metastasis in the early stage and locally advanced groups were 22.9% (11/48) and 46.2% (12/26), respectively, and 58.8% (20/34) and 7.5% (3/37) in the positive and negative lymphovascular invasion groups, respectively (p<0.05). The levels of CD8+ and CD8+ CD28+ T cells in the early stage group were markedly lower than those in the CIN group and the control group (p=0.014, p=0.008, respectively). The ratio of CD4+CD25+/CD4+ in the cervical cancer groups was significantly higher than in the control group (p<0.01). The increased serum squamous cell carcinoma and carcinoembryonic antigen levels and CD4+CD25+/CD4+ ratio were risk factors for cervical cancer by logistic regression analysis (p<0.05).ConclusionsIn patients with cervical cancer, immune function was impaired compared with that in healthy women and patients with CIN, while squamous cell carcinoma and carcinoembryonic antigen levels were increased. Combined detection of the levels of peripheral blood immune cells and serum tumor markers may be helpful for early detection, diagnosis, and prognosis evaluation of patients with cervical cancer.

Download Full-text

Cancer of the vulva: genetic aspects of pathogenesis

GYNECOLOGY ◽

10.26442/2079-5696_2018.4.9-11 ◽

2018 ◽

Vol 20 (4) ◽

pp. 9-11 ◽

Cited By ~ 1

Author(s):

V V Sobolev ◽

Z A Nevozinskaya ◽

A G Soboleva ◽

I M Korsunskaya

Keyword(s):

Squamous Cell Carcinoma ◽

Nucleotide Sequence ◽

Cell Carcinoma ◽

Squamous Cell ◽

Somatic Mutations ◽

Genetic Research ◽

Tp53 Gene ◽

Gene Activity ◽

Genetic Changes ◽

Methylation Of Dna

The review is devoted to genetic research in cancer of the vulva. In genetic changes, the mutation irreversibly changes the nucleotide sequence of DNA, or the number of copies of chromosomes changes per cell. In epigenetics, the nucleotide sequence remains unchanged, but gene activity is regulated by methylation of DNA or modification of histones. Most of the studies analyzed are devoted to the study of mutations in the TP53 gene. Many studies indicate that somatic mutations are more common in HPV-negative than in HPV-positive patients. Epigenetic studies in the main devoted to hypermethylation. The gene CDKN2A is most often studied in epigenetic terms. For most of the studied genes, hypermethylation occurs more often in squamous cell carcinoma of the vulva than in the precursors.

Download Full-text