Polymorphisms of ESR1, UGT1A1, HCN1, MAP3K1 and CYP2B6 are associated with the prognosis of hormone receptor-positive early breast cancer.
In this study, we investigated whether single nucleotide polymorphisms (SNPs) identified by genome-wide association study (GWAS) (MAP3K1, FGFR2, TNRC9, HCN1, and 5p12), and SNPs involved in the metabolism of estrogen (CYP19, COMT, ESR1, and UGT1A1), tamoxifen (CYP2C9, CYP2C19, CYP3A5, and CYP2D6), and chemotherapeutic agents (ABCB1, ALDH3A1, and CYP2B6) are associated with the prognoses of 414 hormone receptor (HR)-positive early breast cancers with negative or 1 to 3 nodal metastases. At a median follow-up period of 10.6 years, 363 patients were alive, and 51 (12.3%) had died. Multiple-adjusted hazard ratios (aHRs) and the corresponding 95% confidence intervals for distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS) in association with the genotypes of 34 SNPs from the above-mentioned 16 genes were evaluated, using the stepwise selection Cox model. We found that the SNP, ESR1-codon325 rs1801132 (G/G+G/C), was associated with a longer DDFS, whereas UGT1A1 rs4148323 (A/A+A/G), and HCN1 rs981782 (A/A+A/C) were significantly associated with poorer DDFS. MAP3K1 rs889312 (C/C) and CYP2B6 rs3211371 (T/C) were significantly associated with poor DFS, DDFS and OS. Among premenopausal women, MAP3K1 rs889312 (C/C), CYP2B6 rs3211371 (T/C), CYP2B6 rs4802101 (T/T), ABCB1 rs2032582 (C/C), and ALDH3A1 rs2231142 (G/G) were significantly associated with poor DDFS, DFS, or OS. Our results provide additional evidence that genetic polymorphisms observed in SNPs are associated with the prognoses of patients with HR-positive breast cancers; this may indicate different treatment strategies for these patients.
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.|Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan.|National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan.
Sung-Hsin
SH
Kuo
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
Shi-Yi
SY
Yang
School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan.|Big Data Research Center, Fu-Jen Catholic University, New Taipei, Taiwan.
San-Lin
SL
You
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Huang-Chun
HC
Lien
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan.
Ching-Hung
CH
Lin
Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Po-Han
PH
Lin
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Chiun-Sheng
CS
Huang
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics / Q000473:pathology; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics*; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D000099148:UGT1A1 Enzyme
D014408:Biomarkers, Tumor; D065702:Cytochrome P-450 CYP2B6; D047628:Estrogen Receptor alpha; D014453:Glucuronosyltransferase; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D048728:MAP Kinase Kinase Kinase 1; D015221:Potassium Channels; D000099148:UGT1A1 Enzyme; C506487:ESR1 protein, human; C578665:HCN1 protein, human; C585599:CYP2B6 protein, human; C482576:MAP3K1 protein, human
GWAS; breast cancer; genetic polymorphism; prognostic factor; survival