Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer.
High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine‑adenine (CA) repeat polymorphism in the P1 promoter region of the insulin‑like growth factor‑1 (IGF‑1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF‑1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low‑grade squamous intraepithelial lesions (L‑SILs), high‑grade squamous intraepithelial lesions (H‑SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF‑1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme‑linked immunosorbent assay. The identification of the IGF‑1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF‑1 in the blood serum were observed between H‑SILs and controls, only (p=0.047). However, the concentration of IGF‑1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H‑SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervical cancer.
Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin 20-081, Poland.
Wojciech
W
Kwasniewski
Department of Molecular Virology, Adam Mickiewicz University, Poznan 61-614, Poland.
Anna
A
Gozdzicka-Jozefiak
Rush Medical College, Rush Medical Center, Chicago, IL 606-12, USA.
Maria
M
Kotarska
Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin 20-081, Poland.
Grzegorz
G
Polak
Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin 20-081, Poland.
Bartlomiej
B
Barczynski
Department of Molecular Virology, Adam Mickiewicz University, Poznan 61-614, Poland.
Justyna
J
Broniarczyk
Molecular Biology Techniques Laboratory, Adam Mickiewicz University, Poznan 61-614, Poland.
Witold
W
Nowak
Department of Cell Biology, Poznan University of Medical Sciences, Poznan 60-806, Poland.
Maria
M
Wolun-Cholewa
Department of Obstetrics and Gynecology, Medical University of Lublin, Lublin 20-081, Poland.
Anna
A
Kwasniewska
Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin 20-081, Poland.
Jan
J
Kotarski
D000328:Adult; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D004279:DNA, Viral / Q000032:analysis; D018900:Dinucleotide Repeats; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000821:virology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology*
D004279:DNA, Viral; D007334:Insulin-Like Growth Factor I