BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

Cao, Yukun; Fu, Xinchu; Wan, Guo‐Xing; Yu, Shiying; Cui, Xiaobin; Li, Li; Jiang, Jinfang; Zheng, Yuqin; Zhang, Wenjie; Li, Feng

doi:10.7314/apjcp.2014.15.11.4513

Cited by 6 publications

(6 citation statements)

References 28 publications

(20 reference statements)

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“…The XRCC2 protein is one of the five paralogs of RAD51, including RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3. The RAD51 paralogs are all required for efficient DNA DSB repair and depletion of any paralog results in significant decreases in homologous recombination frequency, which may lead to more error-prone repair mechanisms, potentially promoting genomic instability and cancer susceptibility [10, 11]. Hamster cells deficient in XRCC2 have been observed to exhibit defects in RAD51 focus formation, a decrease in HRR induced by DSB, hypersensitivity to radiation and DNA cross-linking agents, increased spontaneous chromosome aberrations, and increased chromosome missegregation.…”

Section: Discussionmentioning

confidence: 99%

Electrophoretic mobility shift assays implicate XRCC2:rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer

2019

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Objective A previous study undertaken at our centre to identify common genetic variants associated with sporadic breast cancer in Sri Lankan women showed that the T allele of rs3218550, located in the 3′untranslated region of X-ray repair cross-complementing gene-2 ( XRCC2 ), increased breast cancer risk by 1.5-fold. Dual luciferase reporter assays performed in MCF-7 breast cancer cells showed a putative transcriptional repressor effect exerted mainly by the T allele. Electrophoretic mobility shift assays were conducted to further investigate the interaction of this variant with DNA-binding protein, using nuclear protein extracts derived from MCF-7 cells. Results An allele-specific differential binding was observed. The T allele resulted in differential DNA–protein complex binding as evidenced by the presence of multiple bands of increased intensity compared to the wild-type C allele. This implies possible alteration in binding of regulatory proteins by the variant allele. These results implicate XRCC2 :rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer. XRCC2 is known to play an essential role in homologous recombination repair of DNA double-strand breaks. It is plausible that this variant may be exerting regulatory effects on XRCC2 gene expression leading to altered DNA repair capacity. Further functional studies are warranted to validate this finding.

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Section: Discussionmentioning

confidence: 99%

Electrophoretic mobility shift assays implicate XRCC2:rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer

2019

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“…In a recent study, common genetic polymorphisms in the XRCC2 , PHB , CDH1 , and ATM genes were found to be associated with increased risk of sporadic breast cancer among Sri Lankan postmenopausal women [ 5 ]. Several single nucleotide polymorphisms (SNPs) have been shown to be associated with clinicopathological profiles in sporadic breast cancer in major population groups [ 6 7 8 9 10 11 12 13 ]. However, comparatively few studies have been conducted on under-represented South Asian groups, such as the Sri Lankan population [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Studies conducted on the Chinese population showed that the MDM2 SNP309 G allele increases the risk and the T allele is associated with earlier age of onset of sporadic breast cancers [ 10 ]. Similarly, a polymorphism in exon 11 of the BRCA1 gene, which leads to a glutamine-to-glycine substitution at codon 1,038, was found to be associated with early age of onset of sporadic breast cancer [ 13 ]. Chen et al [ 15 ] observed that CD28 gene polymorphisms contribute to sporadic breast cancer risk and exhibit significant associations with clinicopathological features of sporadic breast cancer in the Chinese Han population.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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PurposeSeveral 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.MethodsA 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.ResultsSeven SNPs showed significant associations with clinicopathological profiles in breast cancer. The G allele of BRCA1:rs799917 (p=0.047; β [standard error; SE]=−1.069 [0.537]) and the G allele of NQO2:rs17136117 (p=0.040, β [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.ConclusionThe 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.

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“…The breast cancer characteristics of Kazakhs include low incidence, early onset age, later clinical stage, and poor prognosis. To date, few studies examining the spectrum of BRCA mutations in China's Kazakh populations have been conducted, and most were performed in Han and Uygur populations (Zhang et al, 2012;Ou et al, 2013;Cao et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Three founder mutations, 187delAG and 5382insC in BRCA1 and 6174delT in BRCA2, have been well-characterized and have an estimated prevalence of 2.5% in the Ashkennazi Jewish population (Roa et al, 1996;Struewing et al, 1997;Fodor et al, 1998). A few studies on BRCA1/2 mutations have been reported in familial or early-onset breast cancer patients from China (Zhang et al, 2012;Cao et al, 2014), but little information is available regarding BRCA1/2 mutations in sporadic breast cancers, particularly in the Kazakh ethnic group in China.…”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of BRCA1/2 gene and pathologic characteristics from Kazakh population with sporadic breast cancer in northwestern China

Yang

Aisimutula

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Mutations in the BRCA1/2 genes are associated with an increased risk of breast cancer, but no large-scale research have examined the BRCA1/2 mutations in Chinese Kazakh women. We evaluated the frequency and distributions of BRCA1 and BRCA2 gene mutations in Kazakh sporadic breast cancer patients and healthy women in China. The association between the clinical-pathologic features of Kazakh breast cancer patients and BRCA1/2 mutations were also investigated. Two unclassified variants (T539M and T1915M) and 16 polymorphisms were detected in this study, 4 of which (G356A, His743, Asn991Asp, Val1269) were detected more frequently in breast cancer patients than in healthy controls. We observed a higher prevalence of BRCA1/2 common sequence alterations and a large number of Kazakh women carrying multiple coexisting BRCA1/2 mutations. The prevalence of BRCA1 mutations was similar to that of BRCA2 mutations. Although no significant differences were observed, BRCA1/2 carriers were generally younger at diagnosis (2015) of wild-type breast cancer patients. BRCA1-associated Kazakh sporadic breast cancers present with high tumor grade, early stage, negative lymph node status, absence of estrogen receptor expression and progesteronepositive status. Estrogen receptor expression was the only predominant histological type in BRCA2 carriers. In this study, we determined the BRCA1 and BRCA2 gene mutation status and determined the association with clinical-pathologic characteristics in a Chinese Kazakh population. Larger population-based screening studies screening the entire coding region of BRCA1/2 are required to evaluate the breast cancer risk induced by the sequence alterations detected in this study.

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BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

Cited by 6 publications

References 28 publications

Electrophoretic mobility shift assays implicate XRCC2:rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer

Electrophoretic mobility shift assays implicate XRCC2:rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer

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

Mutational analysis of BRCA1/2 gene and pathologic characteristics from Kazakh population with sporadic breast cancer in northwestern China

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