scholarly journals Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk

2007 ◽  
Vol 9 (2) ◽  
Author(s):  
Caroline Baynes ◽  
◽  
Catherine S Healey ◽  
Karen A Pooley ◽  
Serena Scollen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Increase Breast Cancer Risk ◽  
Common Variants ◽  
Cancer Susceptibility Genes ◽  
Brca1 Brca2

scholarly journals Development and Validation of a Clinical Polygenic Risk Score to Predict Breast Cancer Risk

2020 ◽  
pp. 585-592 ◽  
Author(s):  
Elisha Hughes ◽  
Placede Tshiaba ◽  
Shannon Gallagher ◽  
Susanne Wagner ◽  
Thaddeus Judkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Cancer History ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Susceptibility Genes

PURPOSE Women with a family history of breast cancer are frequently referred for hereditary cancer genetic testing, yet < 10% are found to have pathogenic variants in known breast cancer susceptibility genes. Large-scale genotyping studies have identified common variants (primarily single-nucleotide polymorphisms [SNPs]) with individually modest breast cancer risk that, in aggregate, account for considerable breast cancer susceptibility. Here, we describe the development and empirical validation of an SNP-based polygenic breast cancer risk score. METHODS A panel of 94 SNPs was examined for association with breast cancer in women of European ancestry undergoing hereditary cancer genetic testing and negative for pathogenic variants in breast cancer susceptibility genes. Candidate polygenic risk scores (PRSs) as predictors of personal breast cancer history were developed through multivariable logistic regression models adjusted for age, cancer history, and ancestry. An optimized PRS was validated in 2 independent cohorts (n = 13,174; n = 141,160). RESULTS Within the training cohort (n = 24,259), 4,291 women (18%) had a personal history of breast cancer and 8,725 women (36%) reported breast cancer in a first-degree relative. The optimized PRS included 86 variants and was highly predictive of breast cancer status in both validation cohorts ( P = 6.4 × 10−66; P < 10−325). The odds ratio (OR) per unit standard deviation was consistent between validations (OR, 1.45 [95% CI, 1.39 to 1.52]; OR 1.47 [95% CI, 1.45 to 1.49]). In a direct comparison, the 86-SNP PRS outperformed a previously described PRS of 77 SNPs. CONCLUSION The validation and implementation of a PRS for women without pathogenic variants in known breast cancer susceptibility genes offers potential for risk stratification to guide surveillance recommendations.

scholarly journals The development of rs7107217 genotyping method and initial study of the association of this gene with the breast cancer risk in Vietnamese women

2019 ◽  
Vol 2 (5) ◽  
pp. 40-49
Author(s):  
Thanh Thi Ngoc Nguyen ◽  
Giau Thi Ngoc Mai ◽  
Hue Thi Nguyen
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Regulation Of Gene Expression ◽  
High Sensitivity ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Cancer Susceptibility Genes ◽  
And Control

Breast cancer is the most common cancer for women around the world. The presence of single nucleotide polymorphisms (SNP) on or near the coding region of breast cancer susceptibility genes can affect the regulation of gene expression, which may increase or decrease the risk of breast cancer. BARX2 was showed to stimulate the expression of ERS1, which involved in the development of breast cancer. SNP rs7107217 on 152kb downstream of the BARX2 could affect the level of protein BARX2 and had been proved to associate with the breast cancer risk in populations similar to Vietnamese, including Chinese and Korean. In this study, rs7107217 was genotyped and initially detemined the association with the breast cancer risk in Vietnamese. Real-time PCR HRM was optimized and used to genotype rs7107217 in 117 breast cancer cases and 105 healthy controls. Thereafter, the correlation of this SNP with the risk of breast cancer was initially determined by analyzing the differences in allelic and genotypic frequencies between cases and control groups. The results showed the optimal rs7107217 genotyping condition was successfully developed with the high sensitivity, specificity, and consistency. SNP rs7107217 had high polymorphism with the frequency of minor allele C of 29.9% and 35.3% in case and control, respectively. SNP rs7107217 had been found no association with the breast cancer risk (C vs A: P = 0.23, OR (95% CI) = 0.79 (0.53 – 1.17)). However with the low reliability of the analysis (11.71%) and the high potential related to the formation of breast cancer, the association between rs7107217 and breast cancer risk in Vietnamese population should be further conducted on a larger sample size to get higher accuracy.

Genetic Identification of Multiple Loci That Control Breast Cancer Susceptibility in the Rat

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 289-299
Author(s):  
Laurie A Shepel ◽  
Hong Lan ◽  
Jill D Haag ◽  
Gerlyn M Brasic ◽  
Megan E Gheen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
African American Women ◽  
Mammary Carcinoma ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Chromosome 8 ◽  
Genetic Identification ◽  
Cancer Susceptibility Genes

Abstract We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.

scholarly journals Germline breast cancer susceptibility genes, tumor characteristics, and survival

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Peh Joo Ho ◽  
Alexis J. Khng ◽  
Hui Wen Loh ◽  
Weang-Kee Ho ◽  
Cheng Har Yip ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Tumor Characteristics ◽  
Breast Cancer Patients ◽  
Luminal B ◽  
Cancer Susceptibility Genes

Abstract Background Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Methods Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. Results PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35–5.17], moderately vs well-differentiated 2.33 [1.56–3.49]), as well as luminal B [HER−] and triple-negative subtypes (vs luminal A 2.15 [1.58–2.92] and 2.85 [2.17–3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2−] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16–2.28]). Conclusions PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

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