Skip to main content
Log in

The ALDH7A1 genetic polymorphisms contribute to development of esophageal squamous cell carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Although the entire etiology of esophageal squamous cell carcinoma (ESCC) is still unclear, alcohol drinking has been identified as a major environmental risk factor. The aldehyde dehydrogenase (ALDH) superfamily members are major enzymes involved in the alcohol-metabolizing pathways. Accumulating evidences demonstrated that ALDH7A1, one of ALDH superfamily members, degrades and detoxifies acetaldehyde generated by alcohol metabolism and have been associated with development and prognosis of multiple cancers. However, it is still unknown if ALDH7A1 single nucleotide polymorphisms (SNPs) contribute to ESCC susceptibility. In this study, we examined the association between sixteen ALDH7A1 SNPs and risk of developing ESCC. Genotypes were determined in 2,098 ESCC patients and 2,150 controls (three independent hospital-based case–control sets from different regions of China). Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by logistic regression. Our data demonstrated that only the ALDH7A1 rs13182402 SNP confer susceptibility to ESCC (For AG genotype, OR = 0.75, 95 % CI = 0.66–0.91, P = 4.8 × 10−6; for GG genotype, OR = 0.59, 95 % CI = 0.41–0.88, P = 0.003). These results are consistent to the biological functions of ALDH7A1 during alcohol metabolism and carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.

    Article  Google Scholar 

  2. Gao YT, McLaughlin JK, Blot WJ, Ji BT, Benichou J, Dai Q, et al. Risk factors for esophageal cancer in Shanghai, China. I. Role of cigarette smoking and alcohol drinking. Int J Cancer. 1994;58(2):192–6.

    Article  CAS  Google Scholar 

  3. Hu J, Nyrén O, Wolk A, Bergström R, Yuen J, Adami HO, et al. Risk factors for oesophageal cancer in northeast China. Int J Cancer. 1994;57(1):38–46.

    Article  CAS  Google Scholar 

  4. Wu C, Kraft P, Zhai K, Chang J, Wang Z, Li Y, et al. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nat Genet. 2012;44(10):1090–7.

    Article  CAS  Google Scholar 

  5. Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet. 2011;43(7):679–84.

    Article  CAS  Google Scholar 

  6. Zhang X, Zhou L, Fu G, Sun F, Shi J, Wei J, et al. The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis. 2014 In press.

  7. Zhang X, Wei J, Zhou L, Zhou C, Shi J, Yuan Q, et al. A functional BRCA1 coding sequence genetic variant contributes to risk of esophageal squamous cell carcinoma. Carcinogenesis. 2013;34(10):2309–13.

    Article  CAS  Google Scholar 

  8. Shi J, Sun F, Peng L, Li B, Liu L, Zhou C, et al. Leukocyte telomere length-related genetic variants in 1p34.2 and 14q21 loci contribute to the risk of esophageal squamous cell carcinoma. Int J Cancer. 2013;132(12):2799–807.

    Article  CAS  Google Scholar 

  9. Liu L, Zhou C, Zhou L, Peng L, Li D, Zhang X, et al. Functional FEN1 genetic variants contribute to risk of hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer. Carcinogenesis. 2012;33(1):119–23.

    Article  Google Scholar 

  10. Alison MR, Guppy NJ, Lim SM, Nicholson LJ. Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose? J Pathol. 2010;222(4):335–44.

    Article  Google Scholar 

  11. Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009;7(3):330–8.

    Article  CAS  Google Scholar 

  12. Deng S, Yang X, Lassus H, Liang S, Kaur S, Ye Q, et al. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One. 2010;5(4):e10277.

    Article  Google Scholar 

  13. van den Hoogen C, van der Horst G, Cheung H, Buijs JT, Lippitt JM, Guzmán-Ramírez N, et al. High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res. 2010;70(12):5163–73.

    Article  Google Scholar 

  14. Prokopczyk B, Sinha I, Trushin N, Freeman WM, El-Bayoumy K. Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009;177(3):173–80.

    Article  CAS  Google Scholar 

  15. Rose AE, Poliseno L, Wang J, Clark M, Pearlman A, Wang G, et al. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression. Cancer Res. 2011;71(7):2561–71.

    Article  CAS  Google Scholar 

  16. Giacalone NJ, Den RB, Eisenberg R, Chen H, Olson SJ, Massion PP, et al. ALDH7A1 expression is associated with recurrence in patients with surgically resected non-small-cell lung carcinoma. Future Oncol. 2013;9(5):737–45.

    Article  CAS  Google Scholar 

  17. Chan CL, Wong JW, Wong CP, Chan MK, Fong WP. Human antiquitin: structural and functional studies. Chem Biol Interact. 2011;191(1–3):165–70.

    Article  CAS  Google Scholar 

  18. Yang CX, Matsuo K, Ito H, Hirose K, Wakai K, Saito T, et al. Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions. Asian Pac J Cancer Prev. 2005;6(3):256–62.

    PubMed  Google Scholar 

  19. Wang J, Wei J, Xu X, Pan W, Ge Y, Zhou C, et al. Replication study of ESCC susceptibility genetic polymorphisms locating in the ADH1B-ADH1C-ADH7 cluster identified by GWAS. PLoS One. 2014;9(4):e94096.

    Article  Google Scholar 

  20. Yang M, Xie W, Mostaghel E, Nakabayashi M, Werner L, Sun T, et al. SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2011;29(18):2565–73.

    Article  CAS  Google Scholar 

  21. Zhou JB, Yang JK, Zhao L, Xin Z. Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population: a case–control study and meta-analysis. Med Sci Monit. 2010;16(6):BR179–83.

    CAS  PubMed  Google Scholar 

  22. Guo Y, Tan LJ, Lei SF, Yang TL, Chen XD, Zhang F, et al. Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis. PLoS Genet. 2010;6(1):e1000806.

    Article  Google Scholar 

  23. Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, et al. Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology. 2009;137(5):1768–75.

    Article  CAS  Google Scholar 

  24. Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, et al. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet. 2010;42(9):764–7.

    Article  CAS  Google Scholar 

  25. Wang LD, Zhou FY, Li XM, Sun LD, Song X, Jin Y, et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet. 2010;42(9):759–63.

    Article  CAS  Google Scholar 

  26. Yao J, Liu L, Yang M. Interleukin-23 receptor genetic variants contribute to susceptibility of multiple cancers. Gene. 2014;533(1):21–5.

    Article  CAS  Google Scholar 

  27. Zhou L, Zhang X, Li Z, Zhou C, Li M, Tang X, et al. Association of a genetic variation in a miR-191 binding site in MDM4 with risk of esophageal squamous cell carcinoma. PLoS One. 2013;8(5):e64331.

    Article  CAS  Google Scholar 

  28. Zhou L, Yuan Q, Yang M. A functional germline variant in the P53 polyadenylation signal and risk of esophageal squamous cell carcinoma. Gene. 2012;506(2):295–7.

    Article  CAS  Google Scholar 

  29. Zhou L, Zhang X, Chen X, Liu L, Lu C, Tang X, et al. GC Glu416Asp and Thr420Lys polymorphisms contribute to gastrointestinal cancer susceptibility in a Chinese population. Int J Clin Exp Med. 2012;5(1):72–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Wu H, Zheng J, Deng J, Hu M, You Y, Li N, et al. A genetic polymorphism in lincRNA-uc003opf.1 is associated with susceptibility to esophageal squamous cell carcinoma in Chinese populations. Carcinogenesis. 2013;34(12):2908–17.

    Article  CAS  Google Scholar 

Download references

Funding supports

This study was funded by the open project of State Key Laboratory of Molecular Oncology (SKL-KF-2013-03), National Natural Science Foundation of China (31271382 & 81201586), Beijing Natural Science Foundation (5122020), Beijing Higher Education Young Elite Teacher Project (YETP0521), Beijing City Talent Training Project (2012D009016000002), and Program for Changjiang Scholars and Innovative Research Team in University (IRT13045).

Conflict of interest

None

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Changchun Zhou or Ming Yang.

Additional information

Haiyong Wang, Lei Tong, and Jinyu Wei contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Tong, L., Wei, J. et al. The ALDH7A1 genetic polymorphisms contribute to development of esophageal squamous cell carcinoma. Tumor Biol. 35, 12665–12670 (2014). https://doi.org/10.1007/s13277-014-2590-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2590-9

Keywords

Navigation