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The associations between immunity-related genes and breast cancer prognosis in Korean women.

ABSTRACT: We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell's C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR)?=?11.99, 95% CI?=?3.62-39.72, P?=?4.84E-05), rs2289278 in TSLP gene (HR?=?4.25, 95% CI?=?2.10-8.62, P?=?5.99E-05) and rs2074724 in HGF gene (HR?=?4.63, 95% CI?=?2.18-9.87, P?=?7.04E-05). In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI?=?1.48-31.06) compared to patients in the 1st tertile of polygenic risk score. Harrell's C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1). The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.

SUBMITTER: Choi J

PROVIDER: S-EPMC4116221 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The associations between immunity-related genes and breast cancer prognosis in Korean women.

Choi Jaesung J Song Nan N Han Sohee S Chung Seokang S Sung Hyuna H Lee Ji-young JY Jung Sunjae S Park Sue K SK Yoo Keun-Young KY Han Wonshik W Lee Jong Won JW Noh Dong-Young DY Kang Daehee D Choi Ji-Yeob JY

PloS one 20140730 7

We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effe ...[more]

PMID: 25075970

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Project description:Importance:Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer testing panels is not well defined. Objective:To determine the risks of breast cancer associated with germline variants in cancer predisposition genes. Design, Setting, and Participants:A study population of 65?057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations between pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of patients with breast cancer and Exome Aggregation Consortium reference controls. The women underwent testing between March 15, 2012, and June 30, 2016. Main Outcomes and Measures:Breast cancer risk conferred by pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes. Results:The mean (SD) age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41?611 consecutively tested white women with breast cancer was estimated at 10.2%. After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN, and TP53), observed pathogenic variants in 5 of 16 genes were associated with high or moderately increased risks of breast cancer: ATM (OR, 2.78; 95% CI, 2.22-3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67), PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88). Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer. Conclusions and Relevance:This study establishes several panel genes as high- and moderate-risk breast cancer genes and provides estimates of breast cancer risk associated with pathogenic variants in these genes among individuals qualifying for clinical genetic testing.

Dataset Information

The associations between immunity-related genes and breast cancer prognosis in Korean women.

Publications

The associations between immunity-related genes and breast cancer prognosis in Korean women.

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