Genetic Loci Controlling Breast Cancer Susceptibility in the Wistar-Kyoto Rat

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 331-339 ◽  
Author(s):  
Hong Lan ◽  
Christina M Kendziorski ◽  
Jill D Haag ◽  
Laurie A Shepel ◽  
Michael A Newton ◽  
...  
Keyword(s):  
Mammary Carcinoma ◽  
Linkage Mapping ◽  
Generalized Linear Model ◽  
Mammary Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Main Effect ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto ◽  
Scan Data

Abstract In this study, the Wistar-Kyoto (WKy) rat was genetically characterized for loci that modify susceptibility to mammary carcinogenesis. We used a genetic backcross between resistant WKy and susceptible Wistar-Furth (WF) rats as a panel for linkage mapping to genetically identify mammary carcinoma susceptibility (Mcs) loci underlying the resistance of the WKy rat. Rats were phenotyped for DMBA-induced mammary carcinomas and genotyped using microsatellite markers. To detect quantitative trait loci (QTL), we analyzed the genome scan data under both parametric and nonparametric distributional assumptions and used permutation tests to calculate significance thresholds. A generalized linear model analysis was also performed to test for interactions between significant QTL. This methodology was extended to identify interactions between the significant QTL and other genome locations. Chromosomes 5, 7, 10, and 14 were found to contain significant QTL, termed Mcs5, Mcs6, Mcs7, and Mcs8, respectively. The WKy alleles of Mcs5, -6, and -8 are associated with mammary carcinoma resistance; the WKy allele of Mcs7 is associated with an increased incidence of mammary cancer. In addition, we identified an interaction between Mcs8 and a region on chromosome 6 termed Mcsm1 (modifier of Mcs), which had no significant main effect on mammary cancer susceptibility in this genetic analysis.

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.

The Expression Level of BRCA2 and Its Changes during Chemotherapy in Patients with Different Pathological Types of Mammary Cancer

2020 ◽  
Author(s):  
Yu HUANG ◽  
Min LUO ◽  
Junqing HUANG ◽  
Shaoxin HUANG ◽  
Liuxia WEI ◽  
...  
Keyword(s):  
Mammary Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Expression Level ◽  
Breast Cancer Susceptibility Gene ◽  
Control Group ◽  
Group A ◽  
Group B ◽  
Experimental Group

Background: We aimed to investigate the expression level of breast cancer susceptibility gene 2 (BRCA2) and its changes during chemotherapy in patients with different pathological types of mammary cancer (MC). Methods: Overall, 102 patients treated in Affiliated Tumor Hospital of Guangxi Medical University, China from April 2013 to August 2017 were enrolled as experimental group, including 58 patients with noninvasive MC (group A) and 44 with invasive MC (group B). Fifty healthy volunteers at the same time were enrolled as control group. The relative expression of BRCA2 in the blood of MC patients was detected by real-time fluorescence quantitative PCR (FQ-PCR). Results: In the experimental group, the expression level of BRCA2 in group A was higher than that in group B before chemotherapy (P<0.001); the expression level in group A and group B 1 month after chemotherapy was higher than that before chemotherapy (P<0.001); the expression level in the both groups 3 months after chemotherapy was higher than that 1 month after chemotherapy (P<0.001); the expression level of BRCA2 in blood of group A increased gradually before, 1 month and 3 months after chemotherapy (P<0.001). The expression level of BRCA2 in blood of group B increased gradually at the same time points (P<0.001). Conclusion: BRCA2 is over-expressed in noninvasive MC patient and under-expressed in invasive MC patient. And it can be used as an index for monitoring the condition of MC patients with different pathological types during chemotherapy.

Mammary carcinoma suppressor and susceptibility genes in the Wistar–Kyoto rat

1992 ◽  
Vol 13 (10) ◽  
pp. 1933-1935 ◽  
Author(s):  
Jill D. Haag ◽  
Michael A. Newton ◽  
Michael N. Gould
Keyword(s):  
Mammary Carcinoma ◽  
Susceptibility Genes ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto

Genetic breast cancer susceptibility variants and prognosis in the prospectively randomized SUCCESS A trial

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
A Hein ◽  
L Häberle ◽  
AB Ekici ◽  
MP Lux ◽  
B Rack ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility
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