Molecular Docking Studies of Botanical Beverage Mix Berries (LIFEGREENTM) against Breast Cancer Cells from Targeted Protein 1QQG, 7B5Q & 7B5O & Uterine Fibroid from Targeted Protein 2AYR, 6T41 & 3GRF

Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.

Cancer risk in relatives of BRCA1/2 pathogenic variant carriers in a large series of unselected patients with breast cancer

Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P<0.001 and RR=21.95,P<0.001;BRCA2:RR=4.19,P<0.001 and RR=4.65,P<0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.

BRCA1、BRCA2在上皮性卵巢癌中的表达及与预后的关系

目的 探讨乳腺癌易感基因1(BRCA1)、乳腺癌易感基因2(BRCA2)在上皮性卵巢癌(EOC)中的表达水平,并分析其与预后的关系。方法 选取2019年1月—2023年6月南通市肿瘤医院收治的98例EOC患者,采集术中切除的新鲜癌组织和癌旁组织,采用实时定量聚合酶链反应(qRT-PCR)检测组织中BRCA1、BRCA2 mRNA表达情况,分析其与临床病理特征的关系,并以Kaplan-Meier生存曲线和Cox回归模型分析其对EOC患者总生存期(OS)和无进展生存期(PFS)的影响。结果 EOC组织BRCA1、BRCA2 mRNA表达量、蛋白相对表达量均低于癌旁组织(P<0.05)。腹腔积液量≥500 mL、国际妇产科学联合会(FIGO)分期Ⅲ—Ⅳ期、有淋巴结转移患者的BRCA1、BRCA2 mRNA表达低于无腹腔积液和腹腔积液量<500 mL、FIGO分期Ⅰ—Ⅱ期及无淋巴结转移患者(P<0.05)。中位随访时间27(9~50)个月,随访率95.92%(4例失访),随访期间39例(39.80%)复发,26例(26.53%)死亡。Kaplan-Meier生存分析显示,BRCA1、BRCA2 mRNA高表达者累积生存率高于低表达者(P<0.05)。BRCA1、BRCA2 mRNA高表达者累积无进展生存率高于低表达者(P<0.05)。多因素Cox回归分析显示化疗≤6疗程、腹腔积液量≥500 mL、FIGO分期Ⅲ+Ⅳ期及BRCA1、BRCA2 mRNA低表达是影响EOC患者OS的独立危险因素(P<0.05)。术后残灶>2 cm、化疗≤6疗程、腹腔积液量≥500 mL及BRCA1、BRCA2 mRNA低表达是影响EOC患者PFS的独立危险因素(P<0.05)。结论 EOC癌变组织中BRCA1、BRCA2异常低表达,BRCA1、BRCA2 mRNA低表达与患者的临床病理特征关系密切,且影响患者PFS及OS。

Detection of Breast Cancer 1 (BRCA1) Gene Using an Electrochemical DNA Biosensor Based on Immobilized ZnO Nanowires

Herein we report an electrochemical DNA biosensor for the rapid detection of sequence (5’ AAT GGA TTT ATC TGC TCT TCG 3’) specific for the breast cancer 1 (BRCA1) gene. The proposed electrochemical genosensor is based on short oligonucleotide DNA probe immobilized onto zinc oxide nanowires (ZnONWs) chemically synthesized onto gold electrode via hydrothermal technique. The morphology studies of the ZnONWs, performed by field emission scanning electron microscopy (FESEM), showed that the ZnO nanowires are uniform, highly dense and oriented perpendicularly to the substrate. Recognition event between the DNA probe and the target was investigated by differential pulse voltammetry (DPV) in 0.1 M acetate buffer solution (ABS), pH 7.00;as a result of the hybridization, an oxidation signal was observed at +0.8 V. The influences of pH, target concentration, and non-complimentary DNA on biosensor performance were examined. The proposed DNA biosensor has the ability to detect the target sequence in the range of concentration between 10.0 and 100.0 μM with a detection limit of 3.32 μM. The experimental results demonstrated that the prepared ZnONWs/Au electrodes are suitable platform for the immobilization of DNA.

Clinical significance of breast cancer susceptibility gene 1 expression in resected non-small cell lung cancer:A meta-analysis

BACKGROUND The clinical significance of breast cancer susceptibility gene 1(BRCA1)in nonsmall cell lung cancer(NSCLC)patients undergoing surgery remains unclear up to now.AIM To explore the relation of BRCA1 expression with clinicopathological characteristics and survival in patients with resected NSCLC.METHODS EMBASE,PubMed,Web of Science,and The Cochrane Library databases were searched to identify the relevant articles.To assess the correlation between the expression of BRCA1 and clinicopathological characteristics and prognosis of patients with resected NSCLC patients,the combined relative risks or hazard ratios(HRs)with their corresponding 95%confidence intervals[CIs]were estimated.RESULTS Totally,11 articles involving 1041 patients were included in the meta-analysis.The results indicated that the expression of BRCA1 was significantly correlated with prognosis of resected NSCLC.Positive BRCA1 expression signified a shorter overall survival(HR=1.60,95%CI:1.25-2.05;P<0.001)and disease-free survival(HR=1.78,95%CI:1.42-2.23;P<0.001).However,no significant association of BRCA1 expression with any clinicopathological parameters was observed.CONCLUSION BRCA1 expression indicates a poor prognosis in resected NSCLC patients.BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Background: Knowledge of HER2/Neu and BRCA1 Genes might be helpful for development of strategies for decreasing the burden of risk of breast cancer. Therefore, the aim of this study to detect the role of HER2/Neu and BRCA1 Genes expression in diagnosis of breast cancer in Sudanese women. Methodology: A total of 100 tissue samples obtained from patients with breast cancer in addition to 50 tissue samples obtained from patients with benign breast lesions, were detected the expression of HER2/Neu and BRCA1 Genes by Polymerase Chain Reaction (PCR). Results: The prevalence of HER2/Neu and BRCA1 Genes, among cases was 6%, and 10% respectively. Conclusion: HER2/Neu and BRCA1 Genes have a considerable contribution to etiology of breast cancer in Sudan that requires further consideration.

不同临床病理特征卵巢浆液性肿瘤患者E-cadherin、BRCA1及P53的表达变化研究

目的:探究不同卵巢浆液性肿瘤中E-钙黏蛋白(E-cadherin)、乳腺癌易感基因1(BRCA1)、P53的表达变化情况。方法:选取2017年12月—2022年2月赣州市妇幼保健院的50例卵巢浆液性癌患者为A组,同时期的40例卵巢交界性浆液性肿瘤患者为B组,30例卵巢良性浆液性囊腺瘤患者为C组。检测及比较三组的组织E-cadherin、BRCA1、P53表达情况,并比较A组中不同年龄、淋巴结转移情况、FIGO分期及不同病理分级者的检测结果。结果:A组的E-cadherin及BRCA1阳性率显著均低于B组及C组,B组则显著均低于C组(P<0.05);A组P53阳性率显著高于B组及C组,B组则显著高于C组(P<0.05)。A组中低级别浆液性癌者E-cadherin和BRCA1阳性率均高于高级别浆液性癌者,低级别浆液性癌者P53阳性率显著低于高级别浆液性癌者,差异均有统计学意义(P<0.05)。A组中不同年龄及FIGO分期者的组织E-cadherin、BRCA1及P53阳性率比较,差异均无统计学意义(P>0.05)。A组有淋巴结转移者E-cadherin和BRCA1阳性率均低于无淋巴结转移者,有淋巴结转移者P53阳性率高于无淋巴结转移者,差异均有统计学意义(P<0.05)。结论:卵巢浆液性癌患者中E-cadherin及BRCA1呈低表达,而P53呈高表达,且不同临床病理情况者存在差异,因此在卵巢浆液性癌的早期筛查检测中有一定的参考价值。

Genetic instability of BRCA1 gene at locus D17S855 is related to clinicopathological behaviors of gastric cancer from Chinese population

AIM： To investigate genetic instability of gene BRCA1 at locus D17S855, and their relationship with clinicopathological characteristics of gastric cancer in Chinese population. METHODS： Microsatellite instability （MSI） and loss of heterozygosity （LOH） of gene BRCA1 at locus D17S855 were compared between 37 samples of gastric cancer and corresponding non-cancerous gastric tissue. RESULTS： MSI at locus D17S855 was positive in 7 of 37 samples of gastric cancer （18.95%）. MSI had a close relationship with TNM staging but no relation with lymph node metastasis, histological type or tumor differentiation. MSI positive frequency in TNM Ⅰ ＋ Ⅱ （31.58%, 6/19） was much higher than that in TNM Ⅲ＋ Ⅳ （5.56%, 1/18）, （P 〈 0.05）. LOH positive rate was 18.92% （7/37）. LOH had no relationship to histological type, tumor differentiation or lymph node metastasis, but LOH positive rate in TNM Ⅲ＋ Ⅳ was 33.33% （6/18）, much higher than that in TNM Ⅰ ＋ Ⅱ （ 5.26%, 1/19）, （P 〈 0.05）. BRCA1 protein was expressed in 14 of 37 samples of gastric cancer. The positive rates of BRCA1 protein in TNM Ⅰ ＋ Ⅱ and TNM Ⅲ＋ Ⅳ were 57.89% and 16.67%, respectively, （P 〈 0.05）. The positive rate of BRCA1 protein was 77.78% in high differentiation samples, 30.77% in middle differentiation and 12.50% in lower differentiation samples, （P 〈 0.05）. CONCLUSION： MSI of BRCA1 gene could be used as a molecular marker in early phases of sporadic gastric cancer in Chinese population. LOH occurs at later period of gastric cancer, therefore, it could be used as prognostic factor.

Effects of 5-Aza-CdR on the Proliferation of Human Breast Cancer Cell Line MCF-7 and on the Expression of Apaf-1 Gene

Hypermethylation in the promoter region of tumor suppressor genes is a common mechanism of gene silencing, which tends to occur in cancer. The effects of 5-Aza-2＇-deoxycytidine （5-Aza-CdR）, a specific DNA methyltransferase inhibitor, on the cell proliferation of human breast cancer cell line MCF-7 and on the expression of Apaf-1 gene were investigated. Human MCF-7 cells were incubated with increasing concentrations of 5-Aza-CdR for 12 to 120 h. The growth inhibition rates of MCF-7 cells were detected by MTT assay. Changes of cell cycle distribution and apoptotic rates of MCF-7 cells were determined by flow cytometry. The expressions of DNA methyltransferase 3b mRNA and Apaf-1 mRNA were measured by reverse transcription polymerase chain reaction （RT-PCR）. Meanwhile, the expression of Apaf-1 protein was detected by Western blotting. The results showed that 5-Aza-CdR significantly inhibited the growth of MCF-7 cells and the growth inhibition rate of MCF-7 cells was significantly enhanced with the concentration of 5-Aza-CdR and the action time. Flow cytometry indicated that 5-Aza-CdR could significantly induce G1/S cell cycle arrest and increase the apoptosis rate of MCF-7 cells. The mRNA and protein expressions of Apaf-1 were up-regulated in MCF-7 cells treated with 5-Aza-CdR, which was accompanied by down-regulation of DNA methyltransferase 3b mRNA. It is concluded that 5-Aza-CdR might retard the growth of tumor ceils and promote the apoptosis of MCF-7 breast cancer cells by inhibiting the expression of DNA methyltransferase 3b and re-activating the Apaf-1 gene expression.

Targeted inhibition of Notch1 gene enhances the killing effects of Paclitaxel on triple-negative breast cancer cells

Objective:To study the influence of targeted inhibition of Notch1 gene on the killing effects of Paclitaxel on triple-negative breast cancer cells.Methods:The triple-negative [estrogen receptor(ER)/progesterone receptor(PR)/human epidermal growth factor receptor 2(Her2)] breast cancer cell line MDA-MB-231 and ER/PR/HER-2-positive breast cancer cell line MCF-7 were cultured,transfected with Notch1-si RNA-overexpression plasmid and blank plasmid,and treated with different concentrations of paclitaxel,and then the cell proliferation activity and apoptosis rate as well as the m RNA expression of Caspase-3,Caspase-9 and Bcl-2 were determined.Results:Paclitaxel could decrease the MDA-MB-231 and MCF-7 cell proliferation activity as well as Bcl-2 mRNA expression,and increase MDA-MB-231 and MCF-7 cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression in dosedependent manners;with the same dose of paclitaxel treatment,the inhibitory effects on MDAMB-231 cell proliferation activity and Bcl-2 m RNA expression as well as the promoting effects on MDA-MB-231 cell apoptosis and mR NA expression of Caspase-3 and Caspase-9 were weaker than those on MCF-7 cell;after 0.5 μM paclitaxel combined with Notch1-siRNA treatment,MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression were significantly lower than those after 0.5 μM paclitaxel combined with control plasmid treatment while cell apoptosis rate and mR NA expression of Caspase-3 and Caspase-9 were higher than those after 0.5 μM paclitaxel combined with control plasmid treatment.Conclusions:Targeted inhibition of Notch1 gene may enhance the killing effects of paclitaxel on triple-negative breast cancer cells by up-regulating the expression of Caspase-3 and Caspase-9 and inhibiting the expression of Bcl-2.

The cancer-testis gene,MEIOB,sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency

Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.

Research progress on the relationship between BRCA1 and hereditary breast cancer

Breast cancer gene 1(BRCA1) gene was the first breast cancel susceptibility gene discovered in familial breast cancer.It has been revealed that BRCA1 can be combined with an array of important protein involved in cell cycle regulation,DNA repair,gene transcription control and apoptosis regulation.It plays a down-regulation effect on tumor growth and an important role in maintaining genomic stability.New research suggests that it also associate with the breast cancer stem cells and microRNA.Its mutations,promoter methylation and ectopic expression may one of the main reasons for the generation and development of hereditary breast cancer.

Low Trichorhinophalangeal Syndrome 1 Gene Transcript Levels in Basal-like Breast Cancer Associate with Mesenchymal-to-epithelial Transition

Objective To investigate trichorhinophalangeal syndrome 1 gene （TRPS-1） expression patterns in different subtypes of breast cancer and its correlations with other genes and survival using microarray data sets. Methods The transcripts of TRPS-1 and its role in survival in breast cancer were analyzed using published microarray data sets-Netherlands Cancer Institute （NKI） cohort and Wang cohort.

BRCA1 and EGFR as prognostic biomarkers in triple negative metastatic breast cancer patients treated with cisplatin plus docetaxel

Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.

The mechanism of BRCA1 participate sporadic breast carcinomas genesis

Objective To elucidate the BRCA1 participated mechanism of genesis and development of sporadic breast cancer through detect the statues of BRCA1 and analysis the relationship with the pathologic and clinic parameters.Methods BRCA1 statues were respectively analyzed in frozen samples or paraffine fixed sporadic breast carcinoma and benign breast tissues by three methods:protein expression by immunohistochemistry(IHC),the methylation of BRCA1 promoter by methylation specific PCR(MSP),gene copy number by interphase fluorescence in situ hybridization(FISH).Results 14.2%(29/204)cases were detected hypermethylation of BRCA1 promoter in sporadic breast cancer.BRCA1 mean copy number in sporadic breast cancer(1.70±0.14)less than those in benign tissues(2.03±0.08,P<0.05),and in sporadic breast cancer with hypermethylation of BRCA1(1.62±0.09)significantly less than in those without hypermethylation(1.84±0.26,P<0.05).The loss copy related to the methylation of BRCA1 promoter.There were significant of 41.1%(88/214)cases no BRCA1 nuclei expression in sporadic breast cancers.Loss expression of BRCA1 had significant correlation with higher histological stages,axillary's lymph nodal metastasis(P<0.01),lower expression of ERα,and overexpression of HER-2 protein(P<0.01).Conclusions There are BRCA1 methylations,loss BRCA1 gene copy and loss protein expression in the sporadic breast cancer,the three statues of BRCA1 is correlated to each other;and the loss expression of BRCA1 protein related to part of pathology and clinic parameters.

Review:BRCA1/2 associated hereditary breast cancer

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCAI and/or BRCA2 genes. In this review, we provide an overview of these two genes, focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial; further studies are needed to elucidate the nature of BRCA 1/2 associated hereditary breast cancers.

The Association between RASSF1 Gene Polymorphisms and Lung Cancer Susceptibility among People in Hubei Province of China

The relationship between Ala/Ser polymorphism in 133 codon of exon 3 region of the RASSF1 gene and genetic susceptibility of lung cancer in Hubei province Han population was investigated by a case-control study. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique was adopted to analyze the polymorphism of codon 133 of exon 3 in the RASSF1 gene of 100 pathologically diagnosed lung cancer patients, and 100 healthy controls. The relationship between different genotypes and the susceptibility of lung cancer was analyzed. Among 200 blood samples from Han people in Hubei Province, including 100 from lung cancer patients and 100 from healthy controls, the frequencies of Ala/Ala, Ala/Ser, Ser/Ser genotype of the RASSF1 in lung cancer patients were 83%, 16%, 1%, and those in healthy controls was 93%, 7%, 0% respectively, with the difference being statistically significant between two groups （P〈0.05）. The individuals with Ala/Ser genotype had higher risk of suffering from lung cancer, with an OR of 2.341, and 95% CI of 1.009-6.393 respectively. It was concluded that RASSF1Ala133Ser was a susceptible genetic factor of lung cancer. Ala/Ser genotype increased the risk of lung cancer.

Polymorphisms at <i>GSTM </i>1, <i>GSTP </i>1, <i>GSTT </i>1 Detoxification Genes Loci and Risk of Breast Cancer in Kazakhstan Population

Associations of null polymorphism (copy number variation) of detoxification genes GSTM1, GSTT1 and GSTP1 (at rs2495636, 105 Ile/Val) with the breast cancer (BC) were assessed in two main ethnic groups of the Republic of Kazakhstan (Kazakhs and Russians). Total number of patients was 181, and of controls 397. Statistically significant difference was observed between BC patients and healthy individuals in alleles frequency (χ2 = 4.89, р = 0.007) of GSTP1 gene at rs2495636 (105 Ile/Val) among the Kazakhs ethnic group. Difference in genotypes distribution (χ2 =5.26, р = 0.076) at this site is approximating to be statistically significant. In the Russian group, no differences were found in genotypes and alleles atrs 2495636 of GSTP1 gene between cases and controls. There was no significant difference between null polymorphism (copy number variation) of GSTM1 and GSTT1 genes among cases and controls in both ethnic groups.

Associations of Polymorphisms of the <i>CYP</i>1<i>A</i>1 and <i>CYP</i>1<i>B</i>1 Cytochrome P450 Genes with Breast Cancer in Kazakhstan

Associations of polymorphisms in rs4646903 site of CYP1A1 and rs1056836 site of CYP1B1 genes with the breast cancer (BC) were studied in two main ethnic groups of Kazakhstan Republic (Kazakhs and Russians). Total number of BC patients was 181, controls—397. The statistically significant differences were revealed in allele frequencies (χ2 = 5.93, р = 0.004) and in genotypes distribution (χ2 = 8.71, р = 0.015) in rs4646903 site of CYP1A1 gene in Kazakh but not in Russian group. The study of CYP1В1 rs1056836 site demonstrated differences in genotype distributions (χ2 = 7.48, р = 0.023) between BC patients and controls in Russian but not in Kazakh ethnic group.

Association among Serum Organochlorine Pesticide Residues, Glutathione S-Transferase M1 Genetic Polymorphism and Female Breast Cancer

Background: The purpose of this study was to evaluate the association among serum organochlorine pesticide residues, glutathione S-transferase M1 genetic polymorphism and female breast cancer. Methods: A 1:1 matched case-control study of 140 newly diagnosed breast cancer patients and 140 non-cancer female patients who consulted the five largest hospitals in the Tangshan city from September 2006 to October 2007. Results: The result showed higher risk of breast cancer among subjects with higher levels of serum DDT and HCH residue, the OR was 3.18 (95%CI, 1.11 - 9.07) and 5.02 (95%CI, 1.64 - 16.56).The value of ORe associated with single environmental factor DDT high residues, and ORg associated with single GSTM1 deletion genotype were respectively 3.86 (1.20 - 12.47) and 1.34 (0.36 - 5.08). The OReg associated with combined action of two factors was 5.59 (1.63 - 18.90), and the value of interaction parameters (γ) equaled 1.24. The value of ORe associated with single environmental factor HCH higher residue and ORg associated with single GSTM1 deletion genotype were respectively 2.73 (0.84 - 8.87) and 1.48 (0.49 - 4.60). The value of OReg associated with combined action of two factors was 3.87 (1.18 - 12.68), and γ equaled 1.38. Conclusion: The results indicated that breast cancer occurrence was the combined result of environmental and genetic factors. The concurrent action of GSTM1 deletion genotype and DDT/HCH enhanced the risk of breast cancer.