Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilo...
Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilot GWAS with a single nucleotide polymorphism (SNP) array 5.0 platform from $Affymetrix^{(R)}$ that contains 443,813 SNPs to search for new genetic risk factors in 89 breast cancer cases and 46 healthy women of Indonesian ancestry. The case-control association of the GWAS finding set was evaluated using PLINK. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratios (ORs) and P values; P values less than $1.00{\times}10^{-8}$ and $5.00{\times}10^{-5}$ were required for significant association and suggestive association, respectively. After analyzing 292,887 SNPs, we recognized 11 chromosome loci that possessed suggestive associations with breast cancer risk. Of these, however, there were only four chromosome loci with identified genes: chromosome 2p.12 with the CTNNA2 gene [Odds ratio (OR)=1.20, 95% confidence interval (CI)=1.13-1.33, $P=1.08{\times}10^{-7}$]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44, $P=6.88{\times}10^{-6}$); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34, $P=4.00{\times}10^{-5}$); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35, $P=4.68{\times}10^{-5}$). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women.
Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilot GWAS with a single nucleotide polymorphism (SNP) array 5.0 platform from $Affymetrix^{(R)}$ that contains 443,813 SNPs to search for new genetic risk factors in 89 breast cancer cases and 46 healthy women of Indonesian ancestry. The case-control association of the GWAS finding set was evaluated using PLINK. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratios (ORs) and P values; P values less than $1.00{\times}10^{-8}$ and $5.00{\times}10^{-5}$ were required for significant association and suggestive association, respectively. After analyzing 292,887 SNPs, we recognized 11 chromosome loci that possessed suggestive associations with breast cancer risk. Of these, however, there were only four chromosome loci with identified genes: chromosome 2p.12 with the CTNNA2 gene [Odds ratio (OR)=1.20, 95% confidence interval (CI)=1.13-1.33, $P=1.08{\times}10^{-7}$]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44, $P=6.88{\times}10^{-6}$); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34, $P=4.00{\times}10^{-5}$); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35, $P=4.68{\times}10^{-5}$). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women.
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문제 정의
We express our heartfelt gratitude to all the study participants and research staff for their contributions to this project. We would like to express our gratefulness to The National Cancer of Dharmais Hospital, Jakarta – Indonesia for its support.
가설 설정
Recently, genome wide association study (GWAS) has generated a systematic way or technique to identify genetic variants for breast cancer, and the most common type of genetic variation is single nucleotide polymorphism (SNP). In this study, we defined genetic variants as chromosome loci that had association with breast cancer risk. Heretofore, approximately 20 susceptibility loci have been identified in GWAS and associated with breast cancer risk (Easton et al.
제안 방법
All subjects were genotyped using Genome-Wide Human SNP Array 5.0 platform (Affymetrix®) that contains 443,813 SNPs to identify genetic variants associated with the susceptibility of breast cancer in Indonesian women.
All subjects who participated in this study provided written inform consent to participate and to permit that their biological samples would be genetically analyzed. This study protocol was approved by the ethical committees of The National Cancer Center of Dharmais Hospital, Jakarta-Indonesia.
As reference, we used four input genotypes from the HapMap populations: Yoruba form Ibadan, YRI; Caucasian from Utah, CEU; Japanese from Tokyo, JPT; and Chinese from Beijing, CHB. By applying the top two associated principal components (eigenvectors), the scatter plot was plotted in order to identify outliers who did not belong to the JPT/CHB cluster. Afterwards, we carried out PCA analysis using only the genotype data from the case and control subjects to assess the population substructure.
For controls, we included healthy voulunteers who had no personal or family history of cancer or other chronic diseases. The collection of blood samples from all subjects were conducted consecutively between 2008 and 2012. There was a matching process based on age between breast cancer patient and control group.
대상 데이터
A total of 89 female breast cancer cases and 46 female healthy controls were included in this study (Table 1). The age of the cases and controls ranged from 31-61 years and 31-74 years, respectively.
In this study we recruited a total of 135 women, consisting of 89 breast cancer patients and 46 healthy controls. Both groups, control and breast cancer patients, were selected from the same population living in Jakarta and involving only subjects that have no relation.
The initial 135 subjects were genotyped using Genome-Wide Human SNP Array 5.0 platform (Affymetrix®) that contains a total of 443,813 SNPs.
Both groups, control and breast cancer patients, were selected from the same population living in Jakarta and involving only subjects that have no relation. The sporadic breast cancer patients were recruited from The National Cancer Center of Dharmais Hospital (Jakarta -Indonesia) between 2008 and 2012. The information related to the history of patients’ disease was acquired from their medical records.
이론/모형
00x10-6), those on the X chromosome and non-polymorphic SNPs; a total of 292,887 SNPs were used for further analysis. Furthermore, for sample quality control, we assessed cryptic relatedness for each sample with identity-by-state method. In order to examine population stratification of this study, we carried out principal component analysis (PCA) using EIGENSTRAT software v5.
00x10-5 were required for significant association and suggestive association, respectively. To have an overview of the association of chromosome position with breast cancer, a Manhattan plot of the study was plotted using Haploview 4.1.
성능/효과
After a standard SNP quality control which excluded SNPs with: Minor Allele Frequency (MAF) < 5%, call rate of < 98%, those that deviated from the Hardy-Weinberg Equilibrium (P≤1.00x10-6), those on the X chromosome and non-polymorphic SNPs; a total of 292,887 SNPs were used for further analysis.
Among 443,813 genotyped SNPs; 31,344 SNPs were dropped from analysis because of call rate < 98% and analysis was continued on the remaining 412,469 SNPs.
(2013) in order to investigate the presence of mutation of CTNNA2 gene in laryngeal carcinomas. Based on their study, they concluded that CTTNA2 was a tumor suppressor gene that often mutated in laryngeal carcinomas.
07 software. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratio (OR) and P value; P values of less than 1.00x10-8 and 5.00x10-5 were required for significant association and suggestive association, respectively. To have an overview of the association of chromosome position with breast cancer, a Manhattan plot of the study was plotted using Haploview 4.
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