Polymorphisms ofESR1, UGT1A1, HCN1, MAP3K1andCYP2B6are associated with the prognosis of hormone receptor-positive early breast cancer

Abstract

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.

MAP3K1 Expression is Associated With Progression and Poor Prognosis of Hormone Receptor-Positive, HER2-Negative Early-Stage Breast Cancer

“…Genome-wide association studies (GWAS) have identi ed several single nucleotide polymorphisms (SNPs), such as MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) rs889312, associated with breast cancer risk [14][15][16]. We recently reported that MAP3K1 rs889312 is closely associated with poor disease-free survival (DFS) and overall survival (OS) in early-stage HR-positive breast cancer [17].…”

Two polymorphisms, rs2046210 and rs3803662, are associated with breast cancer risk in a Vietnamese case-control cohort

“…Among them, seven SNPs (rs2046210 in ESR1, rs1219648 in FGFR2, rs3817198 in LSP1, rs3803662 in TNRC9, rs889312 in MAP3K1, rs10941679 in MRPS30 and rs13281615 in PVT-1) have been found to be strongly associated with breast cancer risk in different populations, not only Asian populations (namely Chinese, Japanese, Pakistani and North Indian), but also European (German), African (Tunisian) and Australian populations, with the majority of the P values being much lower than 0.01. Furthermore, the mutated alleles of these SNPs could increase breast cancer risk significantly with odds ratios (ORs) (and 95% confidence interval (CI)) ranging from 1.07 (1.01 -1.14) to 3.06 (1.79 -5.25) (Liang et al, 2008;Antoniou et al, 2009;Cai et al, 2011;Shan et al, 2012;Guan et al, 2014;Lin et al, 2014;Sawyer et al, 2014;Siddiqui et al, 2014;Zhang et al, 2014;Campa et al, 2015;Ghoussaini et al, 2016;He et al, 2016;Mazhar et al, 2016;Hein et al, 2017;Kuo et al, 2017).…”

Relationships between SNPs and prognosis of breast cancer and pathogenic mechanism

“…There are many studies on correlations between SNPs and prognosis of breast cancer, but conclusions are different. Some researchers believed that rs88931 (MAP3K1) was highly correlated with distant disease‐free survival (DDFS), DFS, and OS of hormone receptor‐positive breast cancer (Kuo et al, ). Yamamoto‐Ibusuki et al () confirmed that homozygous alleles of rs2046210 showed worse relapse‐free survival.…”