Molecular evaluation of HIF-1α gene variation and determination of its frequency, and association with Breast Cancer susceptibility in Saudi Arabia

2020 ◽  
Vol 20 ◽  
Author(s):  
Rashid Mir ◽  
Faisel M. Abu-Duhier ◽  
Ibrahim Altedlawi Albalawi
Keyword(s):  
Breast Cancer ◽  
Saudi Arabia ◽  
Cancer Patients ◽  
Genotype Distribution ◽  
Breast Cancer Patients ◽  
Data Set ◽  
Gene Variation ◽  
Increased Risk ◽  
Significant Difference ◽  
Inheritance Model

Aim: Hypoxia-inducible factor 1 (HIF-1) is responsible in regulating oxygen homeostasis in tissues. HypoxiaInducible Factor α (HIF1-α) is a central effector of the hypoxic response. HIF-1α protein overexpression has been shown to have prognostic relevance in breast cancer. HIF-1α polymorphism is associated with increased breast susceptibility reported by several case controls studies but results remained controversial. Therefore, we studied the relationship between the HIF1α gene polymorphism with the breast cancer risk in Saudi Arabia. Methods: This study was consisted of 114 histologically confirmed Breast cancer patients and 117 sex -matched healthy women. HIF-1α genotyping was done by Amplification refractory mutation system PCR method. The HIF-1α gene genotypes were correlated with different clinicopathological characteristics of breast cancer patients. Results: A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T between breast cancer cases and sex matched healthy controls (p=0.001). Our findings showed that the HIF- 1α variant was associated with an increased risk of Breast cancer for HIF-1α CC vs CT genotype OR = 0. 38, 95% CI = (0. 22 -0. 65), P = 0.005) in codominant inheritance model. The significant association was reported for HIF1A for genotypes CC vs (CT+ TT) OR = 0. 39, 95% CI = (0. 231 -0. 67), P = 0.007) in dominant inheritance model tested. In case of recessive inheritance model, a significant association of HIF-1 alpha gene variants was reported for CC VS -(CC+ CT) vs TT) OR = 3.10, 95% CI = (0. 12- 77.03), P = 0.56). During the allelic comparison, A allele significantly increased the risk of Breast cancer with odd ratio (OR = 0. 66, 95% CI = 0. 53 -1. 21, P = 0.04) and risk ratio RR= 0. 51 (0. 32 -0. 80) P= 0.004). A significant association of HIF1α polymorphism was reported with stage as well as distant metastasis of the disease. Conclusion: A significant association of HIF- 1α-CT heterozygosity and T allele significantly increased the susceptibility and is associated with the metastasis of Breast cancer. Further studies with larger data set and well-designed models are required to validate our findings.

scholarly journals The concentration of matrix metalloproteinase 9 in the tumor and peritumoral tissue as prognostic marker in breast cancer patients

2019 ◽  
Vol 76 (5) ◽  
pp. 476-484 ◽  
Author(s):  
Danijela Cvetkovic ◽  
Bojan Milosevic ◽  
Aleksandar Cvetkovic ◽  
Srdjan Ninkovic ◽  
Jovana Jovankic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Significant Difference ◽  
Peritumoral Tissue

Background/Aim. Breast cancer is one of the most common malignancies among women all over the world. Tumor microenvironment represents one of the main regulators of tumorigenesis. We investigated the role of matrix metalloproteinases 9 (MMP-9) concentration in peritumoral tissue as a prognostic marker in the breast cancer patients. Methods. The ELISA test was used to determine a total MMP-9 concentration in carcinoma and peritumoral tissue sample in the patients with breast cancer. Comparison of MMP-9 protein expression with the clinicopathological parameters was evaluated. Results. Peritumoral tissue at 3 cm distance from the tumor produces more MMP-9 than the tumor itself. The ratio of concentrations of MMP-9 in the tumor and peritumoral tissue considerably changes in favor of peritumoral tissue with the increase of tumor size and the involvement of axillary lymph nodes. In N0 stage, the concentration ratio of MMP-9 in the tumor and peritumoral tissues was 1 : 1.44, but in the N2 stage, the ratio was 1 : 26.5. Conclusion. In patients with breast cancer even in an early stadium there is a change in MMP-9 concentration in peritumoral tissue. We can extract the group of patients at increased risk for the development of lymph node metastasis. A statistically significant difference between the concentrations of MMP-9 in the peritumoral tissue and cancer tissue exists only in case of metastatic disease not in MO stadium implying need for early detection of still unknown metastases in such patients.

Polymorphisms in Cancer Susceptibility Genes XRCC1, RAD51 and TP53 and the Risk of Breast Cancer in Serbian Women

2016 ◽  
Vol 31 (3) ◽  
pp. 258-263 ◽  
Author(s):  
Ana M. Krivokuca ◽  
Milena R. Cavic ◽  
Emina J. Malisic ◽  
Jelena D. Rakobradovic ◽  
Daniela Kolarevic-Ivankovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hereditary Breast Cancer ◽  
Odds Ratio ◽  
Protective Role ◽  
Genotype Distribution ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Young Breast Cancer

Background Thanks to immense improvements in technology over the past few decades, we have witnessed a major shift towards the idea that breast cancer results from a combined effect of multiple common alleles conferring low risk. This study investigates the role of 3 nonsynonymous SNPs in the DNA repair genes XRCC1 (R399Q), RAD51 (G135C) and TP53 (Arg72Pro) in breast cancer in Serbian women. Patients and Methods Cases of BRCA1/2-negative hereditary breast cancer (n = 52), sporadic breast cancer (n = 106) and age-matched cancer-free female controls (n = 104) were obtained from the Institute for Oncology and Radiology of Serbia's blood bank. Restriction fragment length polymorphism analysis was used for genotyping. Descriptive analyses included genotype and allelic frequencies; the odds ratio and 95% confidence interval were calculated as an estimate of the relative risk. Results A significant difference in QQ+RQ versus RR genotype distribution of XRCC1 was observed between hereditary breast cancer patients and cancer-free controls. The association was confirmed among young breast cancer patients from these high-risk families. The existence of 3 recessive alleles in the RAD51 and XRCC1 genotype combination showed an association with hereditary breast cancer. Odds ratio analysis indicated a strong protective role of the RAD51 GG + TP53 ArgArg + XRCC1 RR combined genotype against hereditary breast cancer negative for BRCA1/2 mutations. Conclusions The XRCC1 R399Q polymorphism showed an association with increased breast cancer risk in Serbia, especially in the hereditary form of the disease and in young breast cancer patients. Dominant alleles of RAD51, TP53 and XRCC1 combined genotypes indicated a strong protective role against hereditary breast cancer.

The effects of tamoxifen on homocysteine levels in breast cancer patients

Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 450-453
Author(s):  
Aydan Eroğlu ◽  
Yonca Eğin ◽  
Nejat Akar
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mthfr C677t ◽  
Breast Cancer Patients ◽  
Serum Homocysteine ◽  
Intron 1 ◽  
Increased Risk ◽  
Significant Difference ◽  
The Relationship ◽  
Control Study

AbstractTamoxifen is widely used in the treatment of breast cancer and associated with an increased risk of thromboembolism (TE). An elevated homocysteine is one of the risk factors for TE. The aim of the study was to assess the effect of tamoxifen on serum homocysteine levels in breast cancer patients. We performed a case-control study in 20 female subjects to evaluate the relationship between homocysteine levels, and 5,10-methylenetetrahyrofolate reductase (MTHFR) C677T and dihydrofolate reductase (DHFR) 19-bp intron-1 deletion polymorphisms in breast cancer patients and in control subjects. It was observed that homocysteine levels were decreased during tamoxifen therapy, but this finding was not statistically significant. There was also no statistically significant difference in homocysteine levels between the two groups (p> 0.05). MTHFR C677T and DHFR 19-bp deletion polymorphisms were not associated with serum homocysteine value in either group.

scholarly journals Comparing the efficacy and side-effects of PDLASTA® (Pegfilgrastim) with PDGRASTIM® (Filgrastim) in breast cancer patients: a non-inferiority randomized clinical trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Safa Najafi ◽  
Maryam Ansari ◽  
Vahid Kaveh ◽  
Shahpar Haghighat
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Single Dose ◽  
Side Effects ◽  
Randomized Clinical Trial ◽  
Cancer Patients ◽  
Injection Site Reaction ◽  
Study Groups ◽  
Breast Cancer Patients ◽  
Significant Difference

Abstract Background The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. Methods In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. Results Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. Conclusion It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. Trial registration IRCT20190504043465N1, May 2019.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

scholarly journals Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer

2008 ◽  
Vol 26 (25) ◽  
pp. 4072-4077 ◽  
Author(s):  
Jennifer K. Litton ◽  
Ana M. Gonzalez-Angulo ◽  
Carla L. Warneke ◽  
Aman U. Buzdar ◽  
Shu-Wan Kau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathologic Complete Response ◽  
Operable Breast Cancer ◽  
Obese Patients ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Response To Neoadjuvant Chemotherapy

Purpose To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. Patients and Methods From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI of 25 to < 30 kg/m2), or normal/underweight (BMI < 25 kg/m2). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer–specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. Results Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. Conclusion Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

Attention to diet, exercise, and weight in the oncology clinic: Results of a national patient survey.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10549-10549
Author(s):  
Jennifer A. Ligibel ◽  
Lori J. Pierce ◽  
Catherine M. Bender ◽  
Tracy E Crane ◽  
Christina Marie Dieli-Conwright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Online Survey ◽  
Early Stage ◽  
Cancer Type ◽  
Breast Cancer Patients ◽  
Related Factors ◽  
Increased Risk ◽  
Diet And Exercise ◽  
To Receive

10549 Background: Obesity and related factors are increasingly associated with increased risk of developing and dying from cancer. The American Society of Clinical Oncology (ASCO) conducted a survey of cancer patients to assess their experience in receiving recommendations and referrals related to weight, diet and exercise as a part of their cancer care. Methods: An online survey was distributed to potential participants between March and June 2020 via ASCO channels and patient advocacy organizations, with an estimated reach of over 25,000 individuals. Eligibility criteria included being 18 years, living in the US, and having been diagnosed with cancer. Logistic regression was used to determine factors associated with recommendation and referral patterns. Results: In total, 2419 individuals responded to the survey. Most respondents were female (75.5%), 61.8% had an early-stage malignancy, 38.2% had advanced disease, and 49.0% were currently receiving treatment. Breast cancer was the most common cancer type (36.0%). Average BMI was 25.8 kg/m2. The majority of respondents consumed £2 servings of fruits and vegetables per day (50.9%) and exercised £2 times per week (50.4%). Exercise was addressed at most or some oncology visits in 57.5% of respondents, diet in 50.7%, and weight in 28.4%. Referrals were less common: 14.9% of respondents were referred to an exercise program, 25.6% to a dietitian and 4.5% to a weight management program. In multiple regression analyses, racial and ethnicity minority respondents were more likely to receive advice about diet (Odds Ratio [OR] 1.92, 95% CI 1.56-2.38) and weight (OR 1.64, 95% CI 1.23-2.17) compared to non-Hispanic whites, individuals diagnosed with cancer in the past 5 yrs (vs > 5 yrs) were more likely to receive advice about exercise (OR 1.48, 95% CI 1.23-1.79), and breast cancer patients were more likely to receive advice about exercise (OR 1.37, 95% CI 1.11-1.68) and weight (OR 1.46, 95% CI 1.03-2.07) than other cancer patients. Overall, 74% of survey respondents had changed their diet or exercise after cancer diagnosis. Respondents reporting that their oncologist spoke to them about increasing exercise or eating healthier foods were more likely to report a change in behavior than those whose oncologists did not (exercise: 79.6% vs 69.0%, P < 0.001; diet 81.1% vs 71.4%, P < 0.001). Respondents whose oncologist had spoken to them about exercise were more likely to exercise > 2 times per week compared to respondents whose oncologists did not address exercise (53.5% vs 44.1%, P < 0.001). Conclusions: In a national survey of oncology patients, slightly more than half of respondents reported attention to diet and exercise during oncology visits. Provider recommendations for diet and exercise were associated with positive changes in these behaviors. Additional attention to diet and exercise as part of oncology visits is needed to help support healthy lifestyle change in cancer patients.

Exploring The Clinical Significance of Serum Angiopoietin-2 In Breast Cancer Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Abeer I Abd Elmagid ◽  
Hala Abdel Al ◽  
Wessam El Sayed Saad ◽  
Seham Kamal Mohamed
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Tnm Staging ◽  
Control Group ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Female Patients ◽  
Significant Difference ◽  
Angiopoietin 2

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p &lt; 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p &gt; 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p &gt; 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.

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