Genetic determinants of sporadic breast cancer in Sri Lankan women

Sirisena, Nirmala D.; Adeyemo, Adebowale; Kuruppu, Anchala I.; Neththikumara, Nilaksha; Samaranayake, Nilakshi; Dissanayake, Vajira H. W.

doi:10.1186/s12885-018-4112-4

Cited by 11 publications

(15 citation statements)

References 46 publications

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“…There were no polymorphisms observed in TP53, PTEN, CDH1, CHEK2 and XRCC2. Since it is well established that breast cancer is a regulated by both genetics and epigenetic factors and the underlying genetic mechanisms vary from different population [2,29], it is possible that we do not observed mutations associated with breast cancer, despite, the fact that exon selections are based on the maximum number of codons on which breast cancer related mutations have been reported. Our study provides significant preliminary information, suggesting the need to screen larger panel genes using high throughput sequencing technology, which could further provide gene mutations prevalent in the Mizo population.…”

Section: Discussionmentioning

confidence: 85%

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Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

Zodinpuii¹,

Zothankima²,

Pautu³

et al. 2020

Preprint

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Background: Breast cancer is the most prevalent cancer and leading cause of death among women globally. The present study focuses on screening germline mutations of breast cancer susceptibility genes among the unexplored Mizo breast cancers of culturally and historically homogenous population, living a unique life style habits in terms of diet and tobacco usage. Methods Mutation screening was performed using Sanger sequencing in complete coding region of BRCA1 and frequently mutated exons of TP53, PTEN, CDH1, CHEK2 and XRCC2. Several online mutation prediction tools and databases were used to check the pathogenicity of the polymorphisms observed. Results: We observed eight polymorphisms in total, in which, one variants p.P1544P in BRCA1 gene was found to be novel. No variants were found to have a potential impact on protein since all the polymorphisms are of silent substitutions. No genetic alteration was observed in the studied exons of each of TP53, PTEN, CDH1, CHEK2 and XRCC2. Conclusion: To our knowledge, the present study focusing on familial breast cancer is the first time to analyzed the prevalence of breast cancer susceptibility gene mutations using direct sequencing in Mizo population. Even though, we do not find significant amino acid change, our results suggest the need for further evaluation of broader panel genes and a challenge to screen larger sample size to establish the contribution of these gene mutations in this population.

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Section: Discussionmentioning

confidence: 85%

“…Globally, breast cancer is the top most prevalent cancer and leading cause of mortality among women [1,2]. In 2018, breast and lung cancer holds the same highest position (11.6%) when both the sexes are considered.…”

Section: Introductionmentioning

confidence: 99%

Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

Zodinpuii¹,

Zothankima²,

Pautu³

et al. 2020

Preprint

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“…Study participants were recruited postmastectomy and prior to administration of chemotherapy or radiotherapy. To exclude individuals with inherited cancer syndromes, any participant with a family history of any type of malignancy in their first and second degree relatives was excluded [ 5 ]. Clinicopathological patient data that were retrieved from an electronic database maintained at the Human Genetics Unit included the age of onset of cancer, tumor histologic grade, and lymph node involvement, as well as ER, PR, and HER2 status.…”

Section: Methodsmentioning

confidence: 99%

“…The SNP nexus software tool ( http://snp-nexus.org/ ) was used to select non-synonymous SNPs in the coding regions, 5′-untranslated regions (5′-UTRs), and 3′-untranslated regions (3′-UTRs) of the candidate genes. Coding synonymous and intronic SNPs were excluded [ 5 ]. The SNPs were further filtered using several bioinformatics software tools based on the validation status (dbSNP database; http://www.ncbi.nlm.nih.gov/SNP/ ), evolutionary conservation (MutationTaster; http://www.mutationtaster.org/ ), and presumed functional significance (SNP nexus; http://snp-nexus.org/ ) [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…For most sporadic breast cancers, a significant proportion of the risk is due to multiple low-penetrance susceptibility alleles [ 4 ]. 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 ].…”

Section: Introductionmentioning

confidence: 99%

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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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A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer

Zhu

et al. 2023

J Cancer Res Clin Oncol

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Background Four Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations. Methods Mutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort. Results A total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively). Conclusion This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC.

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Genetic determinants of sporadic breast cancer in Sri Lankan women

Cited by 11 publications

References 46 publications

Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

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

A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer

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