Dataset Information

Evaluation of non-coding region sequence variants and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in individuals of Sri Lankan Sinhalese ethnicity.

ABSTRACT: Mitochondrial DNA (mtDNA) mutations have been reported to be associated with various diseases, including cancer. The present study investigated the mtDNA non-coding region mutations and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in Sri Lankan Sinhalese women. Mitochondrial macro-haplogroups were determined using PCR-restriction fragment length polymorphism, whereas non-coding region sequences were determined using Sanger sequencing. The sequence of the non-coding region was also used to confirm haplogroup status. Neither the mutations in the non-coding region nor the mitochondrial haplogroups that were reported as risk factors in other populations, were determined to be potential risk factors for sporadic breast cancer in the present study. Furthermore, several novel mutations were identified in the present matched pairs case-controlled study. The M65a haplogroup with an additional mutation at position 16311 (P=0.0771) and mutations at the ori-b site (P=0.05) were considered a weak risk factor and protective factor, respectively, for sporadic breast cancer in Sinhalese women. Previous studies have indicated the use of mtDNA mutations as a biomarker; however, the present study showed that such biomarkers need to be validated for individual ethnic groups before they can be recommended for use in the prediction of disease.

SUBMITTER: Tiphania Kotelawala J

PROVIDER: S-EPMC7184950 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Evaluation of non-coding region sequence variants and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in individuals of Sri Lankan Sinhalese ethnicity.

Tiphania Kotelawala Joanne J Ranasinghe Ruwandi R Rodrigo Chrishani C Tennekoon Kamani Hemamala KH Silva Kanishka De K

Biomedical reports 20200317 6

Mitochondrial DNA (mtDNA) mutations have been reported to be associated with various diseases, including cancer. The present study investigated the mtDNA non-coding region mutations and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in Sri Lankan Sinhalese women. Mitochondrial macro-haplogroups were determined using PCR-restriction fragment length polymorphism, whereas non-coding region sequences were determined using Sanger sequencing. The sequence of the non-coding ...[more]

PMID: 32346478

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Project description: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.

Project description:In populations that have a high degree of admixture, such as in Brazil, the sole use of ethnicity self-declaration information is not a good method for classifying individuals regarding their ethnicity. Here, we evaluate the relationship of self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of the mitochondrial DNA (mtDNA), and the genomic ancestry was obtained using 48 autosomal insertion-deletion ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as White, 13.8% as Brown and 10.4% as Black. Classification of the mtDNA haplogroups showed that 46.3% had African mtDNA, and the genomic ancestry analysis showed that the main contribution was European (57.4%). When we looked at the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities from 367 individuals who self-declared as White, 37.6% showed African mtDNA, and they had a high contribution of European genomic ancestry (63.3%) but also a significant contribution of African ancestry (22.2%). Of the 68 individuals who self-declared as Brown, 25% showed Amerindian mtDNA and similar contribution of European and African genomic ancestries. Of the 51 subjects who self-declared as black, 80.4% had African mtDNA, and the main contribution of genomic ancestry was African (55.6%), but they also had a significant proportion of European ancestry (32.1%). The Brazilian population had a uniform degree of Amerindian genomic ancestry, and it was only with the use of genetic markers (autosomal or mitochondrial) that we were able to capture Amerindian ancestry information. Additionally, it was possible to observe a high degree of heterogeneity in the ancestry for both types of genetic markers, which shows the high genetic admixture that is present in the Brazilian population. We suggest that in epidemiological studies, the use of these methods could provide complementary information.

Dataset Information

Evaluation of non-coding region sequence variants and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in individuals of Sri Lankan Sinhalese ethnicity.

Publications

Evaluation of non-coding region sequence variants and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in individuals of Sri Lankan Sinhalese ethnicity.

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