Archives of Toxicology

, Volume 92, Issue 6, pp 1991–1999 | Cite as

Association study of genetic variants in estrogen metabolic pathway genes and colorectal cancer risk and survival

  • Shuwei Li
  • Lisheng Xie
  • Mulong Du
  • Kaili Xu
  • Lingjun Zhu
  • Haiyan Chu
  • Jinfei Chen
  • Meilin WangEmail author
  • Zhengdong ZhangEmail author
  • Dongying GuEmail author


Although studies have investigated the association of genetic variants and the abnormal expression of estrogen-related genes with colorectal cancer risk, the evidence remains inconsistent. We clarified the relationship of genetic variants in estrogen metabolic pathway genes with colorectal cancer risk and survival. A case–control study was performed to assess the association of single-nucleotide polymorphisms (SNPs) in ten candidate genes with colorectal cancer risk in a Chinese population. A logistic regression model and Cox regression model were used to calculate SNP effects on colorectal cancer susceptibility and survival, respectively. Expression quantitative trait loci (eQTL) analysis was conducted using the Genotype-Tissue Expression (GTEx) project dataset. The sequence kernel association test (SKAT) was used to perform gene-set analysis. Colorectal cancer risk and rs3760806 in SULT2B1 were significantly associated in both genders [male: OR = 1.38 (1.15–1.66); female: OR = 1.38 (1.13–1.68)]. Two SNPs in SULT1E1 were related to progression-free survival (PFS) [rs1238574: HR = 1.24 (1.02–1.50), P = 2.79 × 10−2; rs3822172: HR = 1.30 (1.07–1.57), P = 8.44 × 10−3] and overall survival (OS) [rs1238574: HR = 1.51 (1.16–1.97), P = 2.30 × 10−3; rs3822172: HR = 1.53 (1.67–2.00), P = 2.03 × 10−3]. Moreover, rs3760806 was an eQTL for SULT2B1 in colon samples (transverse: P = 3.6 × 10−3; sigmoid: P = 1.0 × 10−3). SULT2B1 expression was significantly higher in colorectal tumor tissues than in normal tissues in the Cancer Genome Atlas (TCGA) database (P < 1.0 × 10−4). Our results indicated that SNPs in estrogen metabolic pathway genes confer colorectal cancer susceptibility and survival.


Estrogen Colorectal cancer Genetic variants SULT2B1 Survival 



This study was partly supported by National Natural Science Foundation of China (81773516 and 81373091), the National Key R&D Program of China (2017YFC0908200), Distinguished Young Scholars of Nanjing (JQX13005), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

204_2018_2195_MOESM1_ESM.docx (364 kb)
Supplementary material 1 (DOCX 364 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingPeople’s Republic of China
  3. 3.Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public HealthNanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.Department of BiostatisticsNanjing Medical UniversityNanjingPeople’s Republic of China
  5. 5.Department of OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingPeople’s Republic of China
  6. 6.Department of Oncology, Nanjing First HospitalNanjing Medical UniversityNanjingPeople’s Republic of China

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