scholarly journals The Influence of rs1859168 Polymorphism on Serum Expression of HOTTIP and Its Target miR-615-3p in Egyptian Patients with Breast Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 733
Author(s):  
Omayma O. Abdelaleem ◽  
Olfat G. Shaker ◽  
Marwa N. AbdelHafez ◽  
Noha K. Abdelghaffar ◽  
Hanaa M. Eid ◽  
...  

Background: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). Methods: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. Results: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). Conclusions: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC.

2019 ◽  
Vol 10 (1) ◽  
pp. 175-183 ◽  
Author(s):  
Isabelle Touwendpoulimdé Kiendrebeogo ◽  
Abdou Azaque Zoure ◽  
Pegdwendé Abel Sorgho ◽  
Albert Théophane Yonli ◽  
Florencia Wendkuuni Djigma ◽  
...  

AbstractBackground and objectiveBreast cancer remains the most common cause of cancer mortality in women. The aim of this study was to investigate associations between genetic variability in GSTM1 and GSTT1 and susceptibility to breast cancer.MethodsGenomic DNA was extracted from blood samples for 80 cases of histologically diagnosed breast cancer and 100 control subjects. Genotyping analyses were performed by PCR-based methods. Associations between specific genotypes and the development of breast cancer were examined using logistic regression to calculate odds ratios [1] and 95% confidence intervals (95%CI).ResultsNo correlation was found between GSTM1-null and breast cancer (OR = 1.83; 95%CI 0.90-3.71; p = 0.10), while GSTT1-null (OR = 2.42; 95%CI 1.17-5.02; p= 0.01) was associated with increased breast cancer risk. The GSTM1/GSTT1 double null was not associated with an increased risk of developing breast cancer (OR = 2.52; 95%CI 0.75-8.45; p = 0.20). Furthermore, analysis found no association between GSTM1-null (OR =1.12; 95%CI 0.08-15.50; p = 1.00) or GSTT1-null (OR = 1.71; 95%CI 0.13-22.51; p = 1.00) and the disease stage of familial breast cancer patients or sporadic breast cancer patients (GSTM1 (OR = 0.40; 95%CI 0.12-1.32; p = 0.20) and GSTT1 (OR = 1.41; 95%CI 0.39-5.12; p = 0.75)). Also, body mass index (BMI) was not associated with increased or decreased breast cancer risk in either GSTM1-null (OR = 0.60; 95%CI 0.21-1.68; p = 0.44) or GSTT1-null (OR = 0.60; 95%CI 0.21-1.68; p =0.45).ConclusionOur results suggest that only GSTT1-null is associated with increased susceptibility to breast cancer development.


2019 ◽  
Vol 19 (8) ◽  
pp. 579-588 ◽  
Author(s):  
Ying Wei ◽  
Xiaolin Wang ◽  
Zhe Zhang ◽  
Mingrui Xie ◽  
Yuyao Li ◽  
...  

Background: Single-nucleotide polymorphisms (SNPs) are important indicators of susceptibility to breast cancer. Objective: To assess the associations between SNPs in the FAM13A, PHLDB1, and CYP24A1 gene and breast cancer risk in the Chinese Han population. Methods: We performed a case-control study including 379 female breast cancer patients and 407 female healthy controls. The three SNPs were genotyped using Agena MassARRAY platform. The χ2 test was used to compare alleles and genotypes frequencies of polymorphisms between case and control groups. Genetic models analyses to assess the associations between SNPs and breast cancer risk by computing odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RegulomeDB and HaploReg databases were used to calculate possible functional effects of polymorphisms. Results: Overall analysis results showed that rs4809957 was associated with an increased risk of breast cancer (allele A: OR = 1.27, 95% CI: 1.03-1.55, p = 0.024; AA vs. GG: OR = 1.80, 95% CI: 1.15–2.82, p = 0.010; recessive model: OR = 1.70, 95% CI: 1.12–2.58, p = 0.012); and rs1059122 was found to be associated with a reduced breast cancer risk in the recessive model (OR = 0.71, 95% CI: 0.51–0.98, p = 0.039). Stratification analysis found significant associations between the three SNPs (rs1059122, rs17748, and rs4809957) and breast cancer risk. Conclusion: Our results suggested that rs1059122 (FAM13A), rs17748 (PHLDB1), and rs4809957 (CYP24A1) might contribute to breast cancer susceptibility in the Chinese Han population. Future studies with large samples are required to confirm our findings, as well as functional studies are needed to explore their function in the breast cancer development.


2020 ◽  
Vol 22 (1) ◽  
pp. 16-20
Author(s):  
Abu Khaled Muhammad Iqbal ◽  
Nasima Akhter ◽  
Hasan Shahrear Ahmed ◽  
Md Rassell ◽  
AMM Yahia ◽  
...  

Background: Malignant neoplastic lesions of the breast are one of the main causes of cancer death among women. In tumor cells the expression status of Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers affecting the treatment approach, management and prognosis of breast carcinoma. Objective: To explore the relation of receptor status in recurrent breast cancer to age and time of recurrence. Methods: This study was conducted in National Institute of Cancer Research and Hospital (NICRH) and included 81 female patients between 20 to 75 years with recurrent breast cancer. Detection of receptor status of ER +ve/-ve, PR +ve/-ve, Her-2+ve/-ve was based on the immunohistochemistry staining of tissue samples of malignant neoplastic lesions prepared from tissue biopsies of patients with recurrent breast cancer. All the information were recorded through the pre-structured data collection sheet and analyzed. Results: This study showed that most of the recurrent breast cancer patients were Triple negative breast cancer (TNBC) (39.5%) and among them most of them were younger patients. Younger patients with TNBC had increased risk of recurrence. Most of the recurrence occurred within 1-2 years. Conclusion: It can be concluded that the assessment of the expression of these biornarkers in recurrent tumors provides reliable information for the treatment approach of locoregional tumors. Journal of Surgical Sciences (2018) Vol. 22 (1): 16-20


2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  

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.


2021 ◽  
pp. jmedgenet-2020-107471
Author(s):  
Pei Sze Ng ◽  
Rick ACM Boonen ◽  
Eldarina Wijaya ◽  
Chan Eng Chong ◽  
Milan Sharma ◽  
...  

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel C. Beachler ◽  
Cynthia de Luise ◽  
Aziza Jamal-Allial ◽  
Ruihua Yin ◽  
Devon H. Taylor ◽  
...  

Abstract Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).


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 ◽  
...  

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.


2017 ◽  
Vol 8 ◽  
pp. 18-22 ◽  
Author(s):  
Masashi Yanae ◽  
Shinichiro Fujimoto ◽  
Kaori Tane ◽  
Maki Tanioka ◽  
Kimiko Fujiwara ◽  
...  

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