3 Biotech

, 9:11 | Cite as

Frequency of I655V SNP of HER-2/neu in colorectal cancer: a study from India

  • Rameez Hasan
  • Deepti Bhatt
  • Shahbaz Khan
  • Vasiuddin Khan
  • Amit Kumar Verma
  • Prahalad Singh Bharti
  • Afzal Anees
  • Kapil DevEmail author
Original Article


The present study was conducted to determine the prognostic significance of I655V SNP (rs1136201) is a genetic one in HER-2 oncoprotein in cases of colorectal cancer (CRC). We conducted a case–control study analysing 83 subjects (naïve primary CRC cases) who underwent CRC biopsy/colectomy and included 57 healthy control subjects. Analysis of HER-2 polymorphism was done by PCR-RFLP technique. The mean age was found to be 55.9 years; median age was 56 years and mode age was 54 years with a range of 43 (30–73). Males constitute 63 (75.9%) and females constitute 20 (24.1%) of patient population. According to gradewise distribution, 12 (14.45%) patients were of Grade I, 53 (63.85%) of Grade II, and 18 (21.68%) were of Grade III. We found out that out of 83 patients, 52 (62.65%) were of homozygous wild type (A/A; Ile/Ile); 27 (32.53%) were of heterozygous type (A/G; Ile/Val) and 4 (4.81%) were of homozygous mutant type (G/G; Val/Val). Allelic frequency of Ile (A) was found out to be 0.79 and that of Val (G) is 0.21 and were not significantly different from the healthy control population. Fischer’s exact p value obtained was 0.86.


HER-2/neu polymorphism I655V (A/G) Colorectal cancer (CRC) PCR-RFLP Prognostic Biomarker 



Colorectal cancer


Human epidermal growth factor receptor


Jamia Millia Islamia


Jawaharlal Nehru Medical College


Aligarh Muslim University


Single nucleotide polymorphism


Polymerase chain reaction


Restriction fragment length polymorphism


Allele frequency database


Invasive ductal carcinoma



The authors are indebted to all the study participants. Rameez Hasan would like to thank and acknowledge University Grants Commission (U.G.C.), Govt. of India and Ministry of Minority Affairs, Govt. of India for providing Maulana Azad National Fellowship (F1-17.1/2013-14/MANF-2013-14-MUS-RAJ-20039 dated 6th Feb. 2014) to him.

Author contributions

RH and KD planned the study. RH, AA, and KD designed the manuscript. AA performed colonoscopic biopsies/colectomy. RH performed laboratory procedures under the guidance of KD. RH wrote the paper. DB, VK, AKV, PSB, and SK helped in revising the manuscript. All the authors reviewed and approved the manuscript.


This work was funded by the University Grants Commission (U.G.C.), Govt. of India through MRP grant awarded to Kapil Dev (MRP-MAJOR-BIOT-2013-34536) vide F. No. 43–84/2014(SR) dated 23rd Sept. 2015.

Compliance with ethical standards

Availability of data and material

We state that research data will not be shared or put in open public domain, as it is forbidden under the policy of JMI and AMU. The data that support the outcomes of this study are accessible from JMI. However, limitations exist in availability of this data, which was used under the authorization for the present study and so is not openly accessible. Data is, however, available from the authors upon reasonable request and with permission of JMI and AMU.

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval & consent to participate

The Institutional Ethics Committee of Jamia Millia Islamia (vide Proposal No. 17/9/10/JMI/IEC/2015 dated 14.01.2016) and Aligarh Muslim University (vide D. No. 2183/FM dated 09.02.2016) has approved the study. A written informed consent was obtained before inclusion in the study.


  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2016) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66(4):683–691CrossRefGoogle Scholar
  2. Bonnington SN, Rutter MD (2016) Surveillance of colonic polyps: are we getting it right? World J Gastroenterol 22(6):1925CrossRefGoogle Scholar
  3. Conradi LC, Styczen H, Sprenger T, Wolff HA, Rodel C, Nietert M, Homayounfar K, Gaedcke J, Kitz J, Talaulicar R, Becker H, Ghadimi M, Middel P, Beissbarth T, Ruschoff J, Liersch T (2013) Frequency of HER-2 positivity in rectal cancer and prognosis. Am J Surg Pathol 37(4):522–531. CrossRefPubMedGoogle Scholar
  4. Dean L (2015) Trastuzumab (herceptin) therapy and ERBB2 (HER2) genotypeGoogle Scholar
  5. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Bray F (2014) Globocan 2012, cancer incidence and mortality worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer, LyonGoogle Scholar
  6. Iqbal N, Iqbal N (2014) Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Mol Biol Int 2014:852748. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Jørgensen JT (2014) Role of human epidermal growth factor receptor 2 in gastric cancer: biological and pharmacological aspects. World J Gastroenterol WJG 20(16):4526CrossRefGoogle Scholar
  8. Jung YS (2017) Is colorectal cancer screening necessary before 50 years of age? Intest Res 15(4):550–551CrossRefGoogle Scholar
  9. Kolligs FT (2016) Diagnostics and epidemiology of colorectal cancer. Visc Med 32(3):158–164CrossRefGoogle Scholar
  10. Marx AH, Burandt EC, Choschzick M, Simon R, Yekebas E, Kaifi JT, Mirlacher M, Atanackovic D, Bokemeyer C, Fiedler W, Terracciano L, Sauter G, Izbicki JR (2010) Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers. Hum Pathol 41(11):1577–1585. CrossRefPubMedGoogle Scholar
  11. McKay J, Loane J, Ross V, Ameyaw M, Murray G, Cassidy J, McLeod H (2002) c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer 86(4):568–573CrossRefGoogle Scholar
  12. Meyer B, Are C (2017) Current status and future directions in colorectal cancer. Springer, IndiaCrossRefGoogle Scholar
  13. Ng CK, Martelotto LG, Gauthier A, Wen H-C, Piscuoglio S, Lim RS, Cowell CF, Wilkerson PM, Wai P, Rodrigues DN (2015) Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification. Genome Biol 16(1):107CrossRefGoogle Scholar
  14. Papewalis J, Nikitin AY, Rajewsky M (1991) G to A polymorphism at amino acid codon 655 of the human erbB-2/HER2 gene. Nucleic Acids Res 19(19):5452–5452CrossRefGoogle Scholar
  15. Paszat L, Sutradhar R, Liu Y, Baxter NN, Tinmouth J, Rabeneck L (2017) Risk of colorectal cancer among immigrants to Ontario, Canada. BMC Gastroenterol 17(1):85CrossRefGoogle Scholar
  16. Patil PS, Saklani A, Gambhire P, Mehta S, Engineer R, De’Souza A, Chopra S, Bal M (2017) Colorectal cancer in India: an audit from a tertiary center in a low prevalence area. Indian J Surg Oncol 8(4):484–490CrossRefGoogle Scholar
  17. Pinto D, Vasconcelos A, Costa S, Pereira D, Rodrigues H, Lopes C, Medeiros R (2004) HER2 polymorphism and breast cancer risk in Portugal. Eur J Cancer Prev 13(3):177–181CrossRefGoogle Scholar
  18. Rajeevan H, Soundararajan U, Kidd JR, Pakstis AJ, Kidd KK (2012) ALFRED: an allele frequency resource for research and teaching. Nucleic Acids Res 40(Database issue):D1010–D1015. CrossRefGoogle Scholar
  19. Riaz SK, Rashid MM, Kayani MA, Arshad Malik MF (2016) Role of HER-2 Ile655Val polymorphism as universal cancer susceptibility marker among different cancers. Arch Iran Med (AIM) 19(6):430–438Google Scholar
  20. Sclafani F, Roy A, Cunningham D, Wotherspoon A, Peckitt C, Gonzalez de Castro D, Tabernero J, Glimelius B, Cervantes A, Eltahir Z, Oates J, Chau I (2013) HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab. Ann Oncol 24(12):3123–3128. CrossRefPubMedGoogle Scholar
  21. Simon K (2016) Colorectal cancer development and advances in screening. Clin Interv Aging 11:967CrossRefGoogle Scholar
  22. Singla H, Munshi A, Banipal RP, Kumar V (2018) Recent updates on the therapeutic potential of HER2 tyrosine kinase inhibitors for the treatment of breast cancer. Curr Cancer Drug Targets 18(4):306–327CrossRefGoogle Scholar
  23. Tai W, Mahato R, Cheng K (2010) The role of HER2 in cancer therapy and targeted drug delivery. J Control Release 146(3):264–275CrossRefGoogle Scholar
  24. Tan LD, Xu YY, Yu Y, Li XQ, Chen Y, Feng YM (2011) Serum HER2 level measured by dot blot: a valid and inexpensive assay for monitoring breast cancer progression. PLoS One 6(4):e18764. CrossRefPubMedPubMedCentralGoogle Scholar
  25. Wagner MJ, Stacey MM, Liu BA, Pawson T (2013) Molecular mechanisms of SH2-and PTB-domain-containing proteins in receptor tyrosine kinase signaling. Cold Spring Harbor Perspect Biol 5(12):a008987CrossRefGoogle Scholar
  26. Wang DD, Ma L, Wong MP, Lee VH, Yan H (2015) Contribution of EGFR and ErbB-3 heterodimerization to the EGFR mutation-induced gefitinib-and erlotinib-resistance in non-small-cell lung carcinoma treatments. PLoS One 10(5):e0128360CrossRefGoogle Scholar

Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  • Rameez Hasan
    • 1
    • 2
  • Deepti Bhatt
    • 1
  • Shahbaz Khan
    • 1
  • Vasiuddin Khan
    • 1
  • Amit Kumar Verma
    • 1
  • Prahalad Singh Bharti
    • 3
  • Afzal Anees
    • 2
  • Kapil Dev
    • 1
    Email author
  1. 1.Department of BiotechnologyJamia Millia IslamiaNew DelhiIndia
  2. 2.Department of SurgeryJawaharlal Nehru Medical College, Aligarh Muslim UniversityAligarhIndia
  3. 3.Department of BiophysicsAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations