The breast cancer genetic risk model based on eight single nucleotide polymorphisms

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

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Common Single-Nucleotide Polymorphisms in DNA Double-Strand Break Repair Genes and Breast Cancer Risk

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-08-0594 ◽

2008 ◽

Vol 17 (12) ◽

pp. 3482-3489 ◽

Cited By ~ 19

Author(s):

K. A. Pooley ◽

C. Baynes ◽

K. E. Driver ◽

J. Tyrer ◽

E. M. Azzato ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Single Nucleotide Polymorphisms ◽

Strand Break ◽

Double Strand Break Repair ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Dna Double Strand Break ◽

Repair Genes

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Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome

Breast Cancer Research and Treatment ◽

10.1007/s10549-011-1600-5 ◽

2011 ◽

Vol 130 (3) ◽

pp. 905-916 ◽

Cited By ~ 19

Author(s):

Hong Shi ◽

Melanie Bevier ◽

Robert Johansson ◽

Ewa Grzybowska ◽

Bowang Chen ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Single Nucleotide Polymorphisms ◽

Clinical Outcome ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Association of Allelic Interaction of Single Nucleotide Polymorphisms of Influx and Efflux Transporters Genes With Nonhematologic Adverse Events of Docetaxel in Breast Cancer Patients

Clinical Breast Cancer ◽

10.1016/j.clbc.2018.04.018 ◽

2018 ◽

Vol 18 (5) ◽

pp. e1173-e1179

Author(s):

Rafid Salim Jabir ◽

Gwo Fuang Ho ◽

Muhammad Azrif Bin Ahmad Annuar ◽

Johnson Stanslas

Keyword(s):

Breast Cancer ◽

Single Nucleotide Polymorphisms ◽

Adverse Events ◽

Cancer Patients ◽

Efflux Transporters ◽

Nucleotide Polymorphisms ◽

Breast Cancer Patients ◽

Single Nucleotide ◽

Allelic Interaction

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Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab633 ◽

2021 ◽

Author(s):

Chaojie Ye ◽

Lijie Kong ◽

Zhiyun Zhao ◽

Mian Li ◽

Shuangyuan Wang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Standard Deviation ◽

Kidney Disease ◽

Single Nucleotide Polymorphisms ◽

Arterial Stiffness ◽

Genetic Risk ◽

Mendelian Randomization ◽

Genetic Risk Score ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

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