The Effect of the Polymorphism on the 5\' Region of the Leptin gene (G2548A) on the Possibility of Breast Cancer in two Studies Groups

Background & Objective: Leptin a hormone secreted from adipose tissue plays a role in regulating energy homeostasis. Polymorphism in the gene structure can alter serum levels of hormone and affect cell function. In this study, the relationship between G2548A polymorphism of the leptin gene with the risk of breast cancer in patients compared with healthy subjects was investigated. Materials and Methods: The blood sample of 158 women with breast cancer and 158 healthy women of the same age was collected and after extracting DNA and amplifying specimens with specific primers, some part of products was digested with HhaI restriction enzyme to determine the genotypes of individuals based on the number of bands formed on the gel. The results were analyzed by statistical analysis including chi-square, and logistic regression. Results: The mean age of the patients was 56.00±0.62 years old and the control groups was 55.45±0.72 years old (p-value =0.037). There was a significant relationship between the smoking level of the two groups (p-value =0.026). The history of relatives of breast cancer patients was positive in 43 (27.22%) patients. Analysis of the results of genotypes showed that the mutant homozygote genotype AA had a significant relationship in two groups and increased by 1.686 the risk of breast cancer (P-Value=0.036, OR:1.686, CI95%:1.033-2.753). Conclusion: The frequency of mutant A allele in the patient group was more than that of the control groups and increased the risk of breast cancer by 1.763 times in carriers. Overall, it can be said that this polymorphism is probably related to breast cancer

The relationship between Human Papillomavirus and Epstein-Barr virus infections with breast cancer of Iranian patients

Background: Breast cancer is the malignancy in humans and other mammals. Several risk factors are involved in their appearance such as higher hormone levels and obesity. Identification of a mouse mammary tumor virus supports a viral etiology for breast tumors in animals. Viruses have been implicated in the development of various cancers, but viral induction for formation breast cancer is controversial. The purpose of this study was investigation of the presence of human papillomavirus (HPV) & Epstein-Barr virus (EBV), in Iranian patients with breast cancer.  As the etiology and progression of breast cancer remain incompletely understood, novel routes of disease pathogenesis are important to consider. Some researchers have been found Human papillomavirus (HPV) and Epstein Barr virus (EBV) in breast carcinomas (BCs). Materials and Methods: Paraffin-embedded sections from 65 female patients with breast carcinoma and 53 breast tissues from patients with fibrocystic disease as control were selected. After DNA extraction and amplification of housekeeping gene (beta-globin), all suitable samples were evaluated for presence of DNA-EBV and DNA-HPV by using PCR (Polymerase Chain Reaction).Results: HPV DNA sequences were detected in 3 of the 53 benign breast tissue samples but none of the breast carcinoma samples was identified. EBV was detected by PCR in 23 of 65 (35.38%) cases of breast cancer specimens and 11 of 53 (20.75%) control samples ( fibroadenoma 7 of 26 (26.92%) and fibrocystic 4 of 27 (14.81%)). A total of 118 samples from 34 cases (81/28%) were positive. Statistically, crammer indicator analysis for EBV infection in tumor samples and normal samples was 0.46 which indicates a significant relationship. Conclusion: Our analysis could not confirm a role of HPV in breast cancer but statistically, significant correlation between EBV infection and breast cancer exists. To demonstrate the possible relationship between viral load and breast cancer, need for epidemiological, biological and molecular mechanisms to clear the virus is involved in the process of carcinogenesis

Impacts of BMI & IL-4 Genetic Polymorphisms (rs2243250 C/T & rs2227284 A/C) on Iranian Breast Cancer Patients: a Pilot Study

Background & Objective: Breast cancer is a phenotypically complex and diverse genetic disease caused by changes in the structure and expression of specific genes. Immune system factors are also involved in the etiology of this neoplasm. This study aimed to evaluate the effect of genetic changes (rs2243250 & rs2227284) on the interleukin 4 gene and body mass index on breast cancer risk in Iranian women. Material & Methods: From women referring to Shohada-Tajrish Hospital, 100 women with breast cancer and 100 healthy women were selected. After blood sampling and DNA extraction, the women’s genotypes were determined using the RFLP-PCR technique. The results were evaluated by SPSS software version 21 and chi-square and logistic regression tests. Results: Analysis of the results with different genetic models showed the effect of rs2243250 on breast cancer (p0.05). People with the CC / TT genotype (polymorphism) were more likely to get breast cancer. Also, the increase in body mass index was significantly associated with both polymorphisms studied. Also, carriers of the TT genotype of rs2243250 polymorphism were more likely to develop breast cancer with aging. Conclusion: Genetic alterations in the IL-4 gene and obesity probably contribute to breast cancer, and carriers of both genetic modifications (CC / TT) are more likely to develop breast cancer

The Correlation between CYP450 Ile462Val Polymorphism and Prostate Cancer in a Group of Iranian Men

Background: Cytochrome P450 plays an important role in pharmaceutical metabolism, steroidal hormones and procarcinogens. CYP1A1 is an enzyme, which is very active in the formation of reactive mediators or injurious agents for DNA. The aim of this study is to evaluate the prevalence rate of genetic polymorphism RS 1048943 gene CYP1A1 in men diagnosed with prostate cancer compared to a control group of healthy men. Methods: This case-control study analysed blood samples from 79 patients with prostate cancer as well as 79 healthy men. Genomic DNA was extracted by the salting out method. After selecting the suitable primers from the papers, the samples were amplified for the considered segment and genotypes of the participants were determined by PCR-RFLP. Results: Individuals with prostate cancer had the following genotypes: AA (31.64%), GG (59.49%) and AG/GA (8.86%) compared to the control group that had genotypes AA (55.69%), GG (29.11%) and AG/GA (15.18%). According to the Hardy–Weinberg equilibrium, the frequency of allele A was 36.7% in the cancer group and 63.29% in the control group. The frequency of allele G was 63.92% in the cancer group and 36.70% in the control group. There were meaningful differences in the frequencies of homozygotes GG (P<0.001) and AA (P=0.002) between patients and controls. Conclusion: Polymorphism RS 1048943 in gene CYP1A1 is related to the risk of developing prostate cancer and it is likely one of the major factors in its occurrence

Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients

Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on &nbsp;Iranian patients under warfarin treatment. Materials and Methods: This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P<0.05 was considered as significance level. Results: The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with &ge;1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (&ndash;1639) GG genotype was significantly higher than GA and AA patients. Conclusion: CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose; furthermore, the daily warfarin dose was not influenced by age, height, weight and sex

Opticin, a small leucine-rich proteoglycan, is uniquely expressed and translocated to the nucleus of chronic lymphocytic leukemia cells

BACKGROUND: Opticin (OPTC) is a member of the small leucine-rich proteoglycan (SLRP) family and is localized particularly in certain extracellular matrices. We have previously reported the unique expression of another SLRP, fibromodulin (FMOD) in the leukemic cells of patients with chronic lymphocytic leukemia (CLL). OPTC is located in the same region as FMOD on chromosome 1 (1q32.1). Cluster up-regulation of genes may be observed in malignancies and the aim of the present study was to analyze the expression of OPTC in CLL cells. METHODS: The expression of OPTC was tested by RT-PCR and realtime qPCR in PBMC from CLL patients, other hematological malignancies and healthy controls. The presence of OPTC protein, and its subcellular localization, was investigated using fractionation methods where the obtained lysate fractions were analyzed by Western blotting. Deglycosylation experiments were performed to investigate the glycosylation status of the CLL OPTC. RESULTS: OPTC was expressed at the gene level in all patients with CLL (n = 90) and in 2/8 patients with mantle cell lymphoma (MCL) but not in blood mononuclear cells of healthy control donors (n = 20) or in tumor samples from nine other types of hematological malignancies. OPTC was detected by Western blot in all CLL samples analyzed (n = 30) but not in normal leukocytes (n = 10). Further analysis revealed a CLL-unique unglycosylated 37 kDa core protein that was found to be located preferentially in the cell nucleus and endoplasmic reticulum (ER) of the CLL cells. CONCLUSIONS: A 37 kDa unglycosylated OPTC protein was detected in ER and in the nucleus of CLL cells and not in healthy control donors. The function of this OPTC core protein remains unclear but its CLL-specific expression and subcellular localization warrants further investigations in the pathobiology of CLL