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Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women.

ABSTRACT: Purpose:Several single nucleotide polymorphisms (SNPs) have been reported to be associated with clinicopathological profiles in sporadic breast cancer based on studies conducted on major population groups. The knowledge of the effects of these common genetic variants in South Asian populations remains limited. The present study aimed to investigate the association between a selected set of SNPs and the clinicopathological profiles in sporadic breast cancer in Sri Lankan women. Methods:A total of 350 postmenopausal women with histologically confirmed invasive breast cancer were genotyped for 58 SNPs located in 36 breast cancer related genes. The clinicopathological factors that were investigated included age of onset, tumor histologic grade, and lymph node involvement, as well as estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status. Association testing was performed using logistic regression models adjusted for confounding factors. Results:Seven SNPs showed significant associations with clinicopathological profiles in breast cancer. The G allele of BRCA1:rs799917 (p=0.047; ? [standard error; SE]=-1.069 [0.537]) and the G allele of NQO2:rs17136117 (p=0.040, ? [SE]=1.901 [0.923]) were found to be associated with age of onset between 50 and 59 years. The C allele of CDH1:rs13689 (odds ratio [OR], 2.121; p=0.033) was found to be associated with ER-positive breast cancer. The A allele of AKT1:rs1130214 (OR, 2.095; p=0.011) and the C allele of NQO2:rs2071002 (OR, 1.632; p=0.045) were associated with HER2-positive breast cancer. The C allele of BRCA2:rs15869 (OR, 1.600; p=0.041) and the C allele of CCND1:rs7177 (OR, 1.555; p=0.041) were associated with high tumor histologic grade. Conclusion:The common genetic variants identified in the AKT1, BRCA1, BRCA2, CCND1, CDH1, and NQO2 genes could serve as potential clinical and prognostic biomarkers in sporadic breast cancer patients. Further studies are required to validate our current findings in other populations.

SUBMITTER: Sirisena ND

PROVIDER: S-EPMC6015979 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women.

Sirisena Nirmala Dushyanthi ND Adeyemo Adebowale A Kuruppu Anchala Ishani AI Samaranayake Nilakshi N Dissanayake Vajira Harshadeva Weerabaddana VHW

Journal of breast cancer 20180620 2

<h4>Purpose</h4>Several single nucleotide polymorphisms (SNPs) have been reported to be associated with clinicopathological profiles in sporadic breast cancer based on studies conducted on major population groups. The knowledge of the effects of these common genetic variants in South Asian populations remains limited. The present study aimed to investigate the association between a selected set of SNPs and the clinicopathological profiles in sporadic breast cancer in Sri Lankan women.<h4>Methods ...[more]

PMID: 29963112

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Project description:BackgroundBreast cancer and its treatment imposes a significant effect in the quality of life (QOL) of women. Being a developing country with contrasting social and cultural norms to the West, Sri Lankan women may have a different experience on QOL following surgical treatment of breast cancer. This study was conducted to evaluate post-treatment QOL in breast cancer patients and to determine its association with the type of surgery.MethodsA cross sectional study was carried out. Fifty four women with non-metastatic breast cancer who underwent surgery for breast cancer at the Professorial Surgical Unit, Colombo during 2015-2018 and completed a minimum of one year follow up after surgery were invited to participate. Fifty-four women who responded were assessed using the validated EORTC QLQ-C30 and QLQ-BR23 questionnaires. Non-parametric tests were used for statistical analyses.ResultsThe mean age was 59 years (range 36-81). A majority (61%, n = 35) underwent mastectomy and the rest (n = 19, 45%) breast conservation surgery (BCS). The mean QLQ-C30 score was 68.8 (range 8.3-100) and the mean scores for physical function, role function, emotional function, cognitive function, and social function were 71.4, 81.5, 77.0, 80.2, and 86.4, respectively. The mean scores for body image, sexual functioning, sexual enjoyment, future perspective, systemic therapy, breast symptoms, arm symptoms, and hair loss assessed by the QLQ-BR23 were 76.4, 18.3, 33.3, 73.6, 30.5, 16.2, 23.4 and 32.7, respectively. No significant differences (P > 0.05) were noted in global health status, physical function, role function, emotional function, cognitive function and social function between BCS and mastectomy. QLQ-BR23 body image, sexual functioning, sexual enjoyment and future perspective also did not differ significantly (p > 0.05) between the two groups.ConclusionsSexual functioning and enjoyment, breast and arm symptoms and hair loss contributed to poor QOL while the impact on global health status including physical, social and emotional functions were minimal. Type of surgery did not appear to be associated with QOL. Future studies with a larger sample sizes will be helpful to further study these factors.

Project description:IntroductionPrevention of cardiovascular disease and diabetes is a priority in low- and middle-income countries, especially in South Asia where these are leading causes of morbidity and mortality. The metabolic syndrome is a tool to identify cardiometabolic risk, but the validity of the metabolic syndrome as a clinical construct is debated. This study tested the existence of the metabolic syndrome, explored alternative cardiometabolic risk characterisations, and examined genetic and environmental factors in a South Asian population sample.MethodsData came from the Colombo Twin and Singleton follow-up Study, which recruited twins and singletons in Colombo, Sri Lanka, in 2012-2015 (n = 3476). Latent class analysis tested the clustering of metabolic syndrome indicators (waist circumference, high-density lipoprotein cholesterol, triglycerides, blood pressure, fasting plasma glucose, medications, and diabetes). Regression analyses tested cross-sectional associations between the identified latent cardiometabolic classes and sociodemographic covariates and health behaviours. Structural equation modelling estimated genetic and environmental contributions to cardiometabolic risk profiles. All analyses were stratified by sex (n = 1509 men, n = 1967 women).ResultsThree classes were identified in men: 1) "Healthy" (52.3%), 2) "Central obesity, high triglycerides, high fasting plasma glucose" (40.2%), and 3) "Central obesity, high triglycerides, diabetes" (7.6%). Four classes were identified in women: 1) "Healthy" (53.2%), 2) "Very high central obesity, low high-density lipoprotein cholesterol, raised fasting plasma glucose" (32.8%), 3) "Very high central obesity, diabetes" (7.2%) and 4) "Central obesity, hypertension, raised fasting plasma glucose" (6.8%). Older age in men and women, and high socioeconomic status in men, was associated with cardiometabolic risk classes, compared to the "Healthy" classes. In men, individual differences in cardiometabolic class membership were due to environmental effects. In women, genetic differences predicted class membership.ConclusionThe findings did not support the metabolic syndrome construct. Instead, distinct clinical profiles were identified for men and women, suggesting different aetiological pathways.

Project description:BACKGROUND:Polycystic ovary syndrome (PCOS), the commonest endocrine disorder affecting young women, appears to be a multigenic trait with contributing genes being unclear. Hence, analysis of polymorphisms in multiple candidate genes is required. Currently available genotyping methods are expensive, time-consuming with limited analytical sensitivity. AIM:(i) Develop and validate high resolution melting (HRM) assay and allele-specific real-time quantitative PCR (AS-qPCR) for genotyping selected SNPs associated with PCOS. (ii) Identify selected SNPs and their association with a Sri Lankan cohort of well-characterized PCOS. METHODS:DNA was extracted from women with well-characterized PCOS from adolescence (n = 55) and ethnically matched controls (n = 110). FTO (Fat mass and obesity associated gene; rs9939609), FSHB (Follicle stimulating hormone beta subunit; rs6169), FSHR (Follicle stimulating hormone receptor; rs6165/rs6166), and INSR (Insulin receptor; rs1799817) genes were genotyped using HRM assay. GnRH1 (Gonadotropin releasing hormone; rs6185), LHB (Luteinizing hormone beta subunit; rs1800447/rs34349826) and LHCGR (Luteinizing hormone/choriogonadotropin receptor; rs2293275) genes were genotyped using AS-qPCR method. Genotyping results were validated using Sanger sequencing. RESULTS:A significant association was observed within FTO gene polymorphism (rs9939609) and PCOS. Genotype frequency of FTO gene (rs9939609)-cases versus controls were TT-36.4% vs.65.4% (p<0.05), AT-23.6% vs.20.9%, AA-40% vs.13.6% (p<0.05). Genotype frequencies of the SNPs GnRH1 (rs6185), FSHB (rs6169), FSHR (rs6165 & rs6166), LHB (rs1800447 & rs34349826), LHCGR (rs2293275) and INSR (rs1799817) were not significantly different between cases and controls (p>0.05). Only the mutant alleles were observed for LHB rs1800447 and rs34349826 SNPs in both groups. The HRM and AS-qPCR assay results had 100% concordance with sequencing results. CONCLUSIONS:FTO gene rs9939609 polymorphism is significantly more prevalent among Sri Lankan PCOS subjects while the other selected SNPs of HPG axis genes and INSR gene showed no association. HRM and AS-qPCR assays provide a reliable, fast and user-friendly genotyping method facilitating wider implication in clinical practice.

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Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women.

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Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women.

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