Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 11/2014

01-11-2014 | Research Article

Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population

Authors: Meenakshi Umar, Rohit Upadhyay, Shaleen Kumar, Uday Chand Ghoshal, Balraj Mittal

Published in: Tumor Biology | Issue 11/2014

Login to get access

Abstract

Recent genome-wide association studies (GWAS) have identified variants in phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal squamous cell carcinoma (ESCC) in Chinese population. Although few studies have replicated this findings in other populations, but results are contradictory. So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population. The genotyping of PLCE1 variants were performed in 293 histopathologically confirmed incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and ethnicity-matched controls using PCR RFLP. All statistical analyses were performed through SPSS version 15.0. Modeling and functional prediction of two non-synonymous variants were carried out using bioinformatics tools. PLCE1 polymorphisms were not associated with susceptibility to ESCC or its clinical phenotypes (tumor location/lymph node metastasis). No interaction with environmental risk factors was found. In silico analysis suggested negligible effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT genotype conferred adverse outcome to ESCC patients. Our study for the first time suggests that GWAS originated PLCE1 variants do not have independent role in susceptibility of ESCC in northern Indian population; however, a novel haplo-tagging SNP rs7922612 may modify survival outcome of ESCC patients.
Appendix
Available only for authorised users
Literature
1.
Takiar R, Nadayil D, Nandakumar A. Projections of number of cancer cases in India (2010–2020) by cancer groups. Asian Pac J Cancer Prev. 2010;11:1045–9.PubMed
2.
McCabe ML, Dlamini Z. The molecular mechanisms of oesophageal cancer. Int Immunopharmacol. 2005;5:1113–30.PubMedCrossRef
3.
4.
Hiyama T, Yoshihara M, Tanaka S, Chayama K. Genetic polymorphisms and esophageal cancer risk. Int J Cancer. 2007;121:1643–58.PubMedCrossRef
5.
Chung CC, Magalhaes WC, Gonzalez-Bosquet J, Chanock SJ. Genome-wide association studies in cancer—current and future directions. Carcinogenesis. 2010;31:111–20.PubMedCentralPubMedCrossRef
6.
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;42:759–63.PubMedCrossRef
7.
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;42:764–7.PubMedCentralPubMedCrossRef
8.
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;43:679–84.PubMedCrossRef
9.
Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006;38:1397–405.PubMedCrossRef
10.
Rhee SG. Regulation of phosphoinositide-specific phospholipase c. Annu Rev Biochem. 2001;70:281–312.PubMedCrossRef
11.
Bourguignon LY, Gilad E, Brightman A, Diedrich F, Singleton P. Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells. J Biol Chem. 2006;281:14026–40.PubMedCrossRef
12.
Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, et al. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant. 2008;23:1291–7.PubMedCrossRef
13.
Wang X, Zhou C, Qiu G, Yang Y, Yan D, Xing T, et al. Phospholipase C epsilon plays a suppressive role in incidence of colorectal cancer. Med Oncol. 2012;29:1051–8.PubMedCrossRef
14.
Bai Y, Edamatsu H, Maeda S, Saito H, Suzuki N, Satoh T, et al. Crucial role of phospholipase Cε in chemical carcinogen-induced skin tumor development. Cancer Res. 2004;64:8808–10.PubMedCrossRef
15.
Li M, Edamatsu H, Kitazawa R, Kitazawa S, Kataoka T. Phospholipase Cε promotes intestinal tumorigenesis of Apc Min /+ mice through augmentation of inflammation and angiogenesis. Carcinogenesis. 2009;30:1424–32.PubMedCrossRef
16.
Ou L, Guo Y, Luo C, Wu X, Zhao Y, Cai X. RNA interference suppressing PLCE1 gene expression decreases invasive power of human bladder cancer T24 cell line. Cancer Genet Cytogenet. 2010;200:110–9.PubMedCrossRef
17.
Luo D, Gao Y, Wang S, Wang M, Wu D, Wang W, et al. Genetic variation in PLCE1 is associated with gastric cancer survival in a Chinese population. J Gastroenterol. 2011;46:1260–6.PubMedCrossRef
18.
Jain M, Kumar S, Lal P, Tiwari A, Ghoshal UC, Mittal B. Association of genetic polymorphisms of N-acetyltransferase 2 and susceptibility to esophageal cancer in north Indian population. Cancer Invest. 2007;25:340–6.PubMedCrossRef
19.
20.
21.
Dupont WD, Plummer Jr WD. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990;11:116–28.PubMedCrossRef
22.
23.
Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B. Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squmaous cell carcinoma. Mutat Res. 2009;663:52–9.PubMedCrossRef
24.
Carlson JM, Heckerman D, Shani G: Estimating false discovery rates for contingency tables. Microsoft Res. 2009.
25.
Sali A, Potterton L, Yuan F, van Vlijmen H, Karplus M. Evaluation of comparative protein modeling by MODELLER. Proteins. 1995;23:318–26.PubMedCrossRef
26.
Kelley LA, MacCallum RM, Sternberg MJ. Enhanced genome annotation using structural profiles in the program 3D-PSSM. J Mol Biol. 2000;299:499–520.PubMedCrossRef
27.
Morris AL, MacArthur MW, Hutchinson EG, Thornton JM. Stereochemical quality of protein structure coordinates. Proteins. 1992;12:345–64.PubMedCrossRef
28.
29.
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.PubMedCentralPubMedCrossRef
30.
Jain M, Kumar S, Upadhyay R, Lal P, Tiwari A, Ghoshal UC, et al. Influence of apoptosis (BCL2, FAS), cell cycle (CCND1) and growth factor (EGF, EGFR) genetic polymorphisms on survival outcome: an exploratory study in squamous cell esophageal cancer. Cancer Biol Ther. 2007;6:1553–8.PubMedCrossRef
31.
Bunney TD, Harris R, Gandarillas NL, Josephs MB, Roe SM, Sorli SC, et al. Structural and mechanistic insights into RAS association domains of phospholipase C epsilon. Mol Cell. 2006;21:495–507.PubMedCrossRef
32.
Hu H, Yang J, Sun Y, Yang Y, Qian J, Jin L, et al. Putatively functional PLCE1 variants and susceptibility to esophageal squamous cell carcinoma (ESCC): a case–control study in eastern Chinese populations. Ann Surg Oncol. 2012;19:2403–10.PubMedCrossRef
33.
Gu H, Ding G, Zhang W, Liu C, Chen Y, Chen S, et al. Replication study of PLCE1 and C20orf54 polymorphism and risk of esophageal cancer in a Chinese population. Mol Biol Rep. 2012;39:9105–11.PubMedCrossRef
34.
Zhou RM, Li Y, Wang N, Liu BC, Chen ZF, Zuo LF. PLC-ε1 gene polymorphisms significantly enhance the risk of esophageal squamous cell carcinoma in individuals with a family history of upper gastrointestinal cancers. Arch Med Res. 2012;43:578–84.PubMedCrossRef
35.
Palmer AJ, Lochhead P, Hold GL, Rabkin CS, Chow WH, Lissowska J, et al. Genetic variation in C20orf54, PLCE1 and MUC1 and the risk of upper gastrointestinal cancers in Caucasian populations. Eur J Cancer Prev. 2012;21:541–4.PubMedCentralPubMedCrossRef
36.
Bye H, Prescott NJ, Lewis CM, Matejcic M, Moodley L, Robertson B, et al. Distinct genetic association at the PLCE1 locus with oesophageal squamous cell carcinoma in the South African population. Carcinogenesis. 2012;33:2155–61.PubMedCentralPubMedCrossRef
37.
Umar M, Upadhyay R, Khurana R, Kumar S, Ghoshal UC, Mittal B. Evaluation of MTHFR677C > T polymorphism in prediction and prognosis of esophageal squamous cell carcinoma: a case-control study in a northern Indian population. Nutr Cancer. 2010;62:743–9.PubMedCrossRef
38.
Upadhyay R, Khurana R, Kumar S, Ghoshal UC, Mittal B. Role of survivin gene promoter polymorphism (−31G>C) in susceptibility and survival of esophageal cancer in northern India. Ann Surg Oncol. 2011;18:880–7.PubMedCrossRef
39.
Umar M, Upadhyay R, Kumar S, Ghoshal UC, Mittal B. CASP8–652 6N del and CASP8 IVS12–19G>A gene polymorphisms and susceptibility/prognosis of ESCC: a case control study in northern Indian population. J Surg Oncol. 2011;103:716–23.PubMedCrossRef
40.
van Leeuwen DM, van Agen E, Gottschalk RW, Vlietinck R, Gielen M, van Herwijnen MH, et al. Cigarette smoke-induced differential gene expression in blood cells from monozygotic twin pairs. Carcinogenesis. 2007;28:691–7.PubMedCrossRef
Metadata
Title
Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population
Authors
Meenakshi Umar
Rohit Upadhyay
Shaleen Kumar
Uday Chand Ghoshal
Balraj Mittal
Publication date
01-11-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2458-z

Other articles of this Issue 11/2014

Tumor Biology 11/2014 Go to the issue

Research Article

Downregulation of a long noncoding RNA-ncRuPAR contributes to tumor inhibition in colorectal cancer

Research Article

Cbl-b accelerates trypsin-induced cell detachment through ubiquitination and degradation of proline-rich tyrosine kinase 2

Research Article

Designing a recombinant chimeric construct contain MUC1 and HER2 extracellular domain for prediagnostic breast cancer

Research Article

CCAR2 deficiency augments genotoxic stress-induced apoptosis in the presence of melatonin in non-small cell lung cancer cells

Research Article

Cryoablation plus chemotherapy in colorectal cancer patients with liver metastases

Research Article

Molecular regulation of ovarian cancer cell invasion
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits