IntechOpen

Home > Books > Genetic Polymorphisms - New Insights

Open access peer-reviewed chapter

HER2Ile655Val Polymorphism and Risk of Breast Cancer

Written By

Tung Nguyen-Thanh, Thong Ba Nguyen and Thuan Dang-Cong

Submitted: 14 June 2021 Reviewed: 15 July 2021 Published: 21 August 2021

DOI: 10.5772/intechopen.99482

Genetic Polymorphisms IntechOpen
Genetic Polymorphisms New Insights Edited by Mahmut Çalışkan

From the Edited Volume

Genetic Polymorphisms - New Insights

Edited by Mahmut Çalışkan

Book Details Order Print

Chapter metrics overview

306 Chapter Downloads

View Full Metrics
Advertisement

Abstract

HER2 plays a vital role in the development and progression of several types of human cancer, so the HER2 becomes one of major targets for HER2-positive breast cancer treatment. Several reports have shown that the HER2 oncogene expression relates to clinicopathological factors in cancer patients. HER2Ile655Val single nucleotide polymorphism associates with malignant tumors, including prostate cancer, colorectal cancer, osteosarcoma, gastric cancer, uterine cervical carcinoma, fibroadenoma, and breast cancer. To understand the precise association, this chapter was described to estimate the association between HER2Ile655Val single nucleotide polymorphism and susceptibility to breast cancer. Our findings suggest that the Val allele in HER2 codon 655 single nucleotide polymorphism is strongly associated with the risk of breast cancer. HER2Ile655Val single nucleotide polymorphism might also be a susceptibility factor that favors early-onset breast cancer.

Keywords

  • single nucleotide polymorphism (SNP)
  • HER2Ile655Val
  • rs1136201
  • breast cancer
  • early-onset
  • meta-analysis

1. Introduction

Breast cancer is the most common cancer among women, increasing incidence in most countries, representing a public health threat [1, 2]. Breast cancer is considered the leading cause of women’s deaths worldwide [3]. More than two million were newly diagnosed with breast cancer in women worldwide in 2018 [3, 4]. There will be an estimated 18.1 million new cancer cases and 9.6 million cancer deaths in 2018. In the United States, breast cancer caused 42,000 deaths in 2017 [5]. There is a link with aging, especially among women aged 45 to 65, and it is increasing among younger women [6, 7, 8].

Human epidermal growth factor receptor 2 (HER2), also known as c-erbB2 and neu, is located on human chromosome 17q21 and is responsible for encoding a 185-kDa cross-membrane glycoprotein receptor. HER2 belongs to the ErbB family of growth factor receptors with intrinsic tyrosine kinase activity. The members of this family take the form of homodimer and heterodimer when activated via cell growth, specifically chemical and invasion [9, 10]. HER2 overexpression is seen in breast cancer, gastric cancer, and ovarian cancer [11]. HER2-targeted therapies have significantly enhanced HER2-positive breast cancer patients [12, 13]. Targets in downstream or resistant pathways of particular interest in HER2-positive breast cancer include mTOR, PI3K, IGF-1R, Akt, HSP90, and VEGF that allow cell development, survival, and differentiation [14, 15, 16, 17].

Several studies have independently discovered the association between HER2Ile655Val single nucleotide polymorphism and different benign and malignant tumors. The association between HER2Ile655Val SNP and the risk of breast cancer, especially early-onset breast cancer, has also been investigated; however, these results are inconclusive and controversial. Several articles have shown the association of HER2Ile655Val SNP with an increased risk of early-onset breast cancer in Chinese, Australian, and Taiwanese women [18, 19, 20, 21]. Nonetheless, the association has not been observed in other studies [22, 23, 24]. In the present chapter, we aimed to obtain a more reliable estimate of the association between HER2Ile655Val SNP and the risk of breast cancer and susceptibility to early-onset breast cancer.

Advertisement

2. The role of HER2 in breast cancer

The proto-oncogene HER2/neu (C-erbB-2) has been localized to chromosome 17q21.1 and encodes a transmembrane tyrosine kinase growth factor receptor [25]. HER2 (human epidermal growth factor receptor 2) is a member of the epidermal growth factor receptor family, encodes a 185 kDa transmembrane glycoprotein with tyrosine kinase activity [26]. Most studies on HER2 found this gene was involved in inducing mammary carcinogenesis. HER2/neu gene amplification has been associated with the development of breast cancer [27].

HER2 is one of the biomarkers that play an essential role in breast cancer classification. Based on ER, PR, HER2, Ki-67 marker, breast cancer can be divided into five groups: Luminal A (ER+ or PR+; HER2-; Ki67 low), Luminal B HER2-negative (ER+ or PR+; HER2-; Ki67 high), Luminal B HER2-positive (ER+ or PR+; HER2+; Ki67 any), HER2-overexpression (ER-; PR-; HER2+; Ki67 any), Triple-negative (ER-; PR-; HER2-; Ki67 any) [28]. In addition, classification based on HER2 expression provides enhanced and essential therapeutic guidance [29]. Patients with subtype absence HER2 expression will have a poor prognosis and not receive the most benefit from chemotherapy [30].

HER2 is a human epidermal growth factor receptor (HER/EGFR/ERBB) family member. The basic structure of the epidermal growth factor receptor was described in Figure 1. In the extracellular domain, LD1 and LD2 are two repeated ligand-binding domains. CR1 and CR2 are two repeated cysteine-rich regions. TM indicates the short transmembrane spanning sequences. In the intracellular domain, TK is a catalytic tyrosine kinase, and CT is the carboxyl-terminal tail. Circled Ps are the phosphorylation sites within the TK and CT regions [31].

Figure 1.

HER2 molecular pathways approaches for HER2 positive breast cancer therapy (modified from Lv et al. 2016) [31].

Schematic diagram of HER2 signaling pathways is shown in Figure 1. Upon ligand binding, dimerization between receptors of the EGFR family and HER2 receptor is induced. The homodimers or heterodimers after that, stimulate a serial of signaling cascades. Among various signaling pathways, the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are the two major and most studied pathways which take a pivotal role in tumor proliferation and anti-apoptosis. The whole signal transduction process can be divided into three sections: signal input (ligand-binding and dimerization), signal processing (a series of signaling cascades), and signal output (corresponding cellular processes) [31].

HER2 molecular pathways approach for HER2-targeted therapeutic strategies have the potential to adopt the HER2 overexpression tumor cells. Drugs targeting HER2 may include monoclonal antibodies that downregulate HER2 expression by binding to the extracellular domain (such as Trastuzumab, Pertuzumab …), small molecular tyrosine kinase inhibitors (Lapatinib, Afatinib, Neratinib …), which compete for ATP-binding to block HER2 signaling, antibody-drug conjugates (such as trastuzumab emtansine, called T-DM1), heat shock protein 90 inhibitors (hsp90) and inhibitors of downstream signal molecules (Targeting mTOR, PI3K/Akt …) (Figure 1) [31, 32].

HER2 amplified or overexpressed in approximately 15–20% of breast cancer and associated with the aggressive clinical feature of absence therapy [33, 34, 35]. The IHC method of HER2 protein detection is advantageous, convenient, inexpensive, and only requires conventional microscopy. However, the results may be influenced by the time and the fixation protocol, the antibody clone, and it is challenging to apply the score sheet to have accurate conclusions. Therefore, for an ambiguous result obtained by immunohistochemical staining, the actual state of HER2 gene amplification should be assessed by performing fluorescent in situ hybridization (FISH) or dual chromogenic in-situ hybridization (DISH) because of its high accuracy and reliability, although expensive [36]. HER2 gene amplification and protein overexpression are important not only as a prognostic factor but also as a predictive clinical response to anti-HER2 therapeutic [37, 38]. Moreover, overall survival in patients treating with HER2-targeted therapy was higher than in patients without treatment [39].

The correlation between HER2 gene expression and breast cancer is not clear. According to most studies, it is thought that HER2 overexpression is a poor prognostic factor [40]. The breast cancer parameters such as lymph node metastases, tumor grade, cell proliferation were reported that associated with the gene expression of HER2 [41, 42]. In the initial reports, HER2/neu amplification was a significant predictor of early relapse and death in breast cancer. HER2 gene amplification has a significant predictor of both disease-free survival and time to relapse in breast cancer patients [43, 44]. However, several authors demonstrated that amplification of the HER2 gene relate to ER, PR status but not correlate with age, tumor size, and lymph node [45].

Advertisement

3. HER2Ile655Val single nucleotide polymorphism

Several studies have independently discovered the association between HER2Ile655Val SNP and different types of benign and malignant tumors, including breast cancer, prostate cancer, colorectal cancer, osteosarcoma, gastric cancer, uterine cervical carcinoma, and fibroadenoma [46, 47, 48, 49, 50, 51, 52, 53]. Riaz et al. conducted meta-analysis research and concluded that HER2Ile655Val SNP is significantly correlated with six significant types of cancer (breast, ovarian, uterine, lung, thyroid, and gastric), suggesting that carriers of the Val allele and Val/Val genotype may be linked with an elevated risk of these cancers [54].

Single nucleotide polymorphisms residing in regulatory or functionally relevant gene regions may affect protein function [55]. HER2Ile655Val SNP has been identified in the transmembrane domain-coding region of the HER2 gene at codon 655, encoding either isoleucine (Ile: ATC) or valine (Val: GTC) [53, 56]. Substitution of these two amino acids can alter the hydrophobicity of proteins, affecting the shape stability of the regions in the protein [57, 58]. Fleishman et al. found that substitution of Val for Ile in this position of the transmembrane region will destabilize the formation of active HER2 dimers, leading to reduced receptor activation and tyrosine kinase activity, even under conditions of HER2 overexpression [59]. The association between the HER2Ile655Val SNP and the risk of breast cancer has been widely investigated in populations worldwide [18, 19, 23, 24, 53, 55, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92].

Advertisement

4. HER2Ile655Val single nucleotide polymorphism contributes to breast cancer risk

Previous meta-analyses by Tao W et al. 2009 [93], Lu S et al. 2010 [94], Wang H et al. 2013 [95], Chen W et al. 2014 [47], and Krishna BM et al. 2018 [96] found that HER2Ile655Val SNP is associated significantly with an increased risk of breast cancer, particularly in young women. However, a meta-analysis by Ma Y et al. 2011 revealed that HER2Ile655Val SNP is not associated with breast cancer susceptibility [97].

Our recent meta-analyses further demonstrate the potential contribution of HER2Ile655Val single nucleotide polymorphism to the oncogenesis of breast cancer [98]. The meta-analysis showed that the HER2 codon 655 Val allele was significantly associated with an increased risk of breast cancer in an allele genetic model (additive model, RR 1.21, 95% CI 1.07–1.36; I2 = 61.0%; n = 16). There was a 21% significant increase in the risk of breast cancer in subjects who were Val carriers (Ile/Val and Val/Val) (dominant model, RR 1.21, 95% CI 1.06–1.38; I2 = 58.0%; n = 16). The recessive model HER2 codon 655 was not associated with the risk of breast cancer (RR 1.26, 95% CI 0.99–1.60; I2 = 23.6%; n = 15). There was publication bias in the studies (Begg’s funnel plot was symmetric; additive model, Egger’s test t = 5.44, P for bias = 0.000, n = 16; dominant model, Egger’s test t = 4.92, P for bias = 0.000, n = 16; recessive model, Egger’s test t = 4.35, P for bias = 0.001, n = 15) (Figure 2).

Figure 2.

The association between HER2Ile655Val SNP and the risk of breast cancer in worldwide populations (modified from Nguyen Thanh et al. 2021) [98]. A. Forest plot for the association between HER2Ile655Val SNP and breast cancer risk; B. Funnel plot evaluating publication bias among studies included in the meta-analysis.

The molecular mechanism of HER2Ile655Val SNP, a non-polar to non-polar amino acid mutation, has been investigated in previous studies. Using computational exploration, Fleishman et al. 2002 proposed that the transmembrane region of the HER2 homodimer can exist in two stable conformations, either in an active or inactive form. The dimer mediated by the C-terminal dimerization motif is more durable than the dimer formed by the N-terminal motif. The authors found that substitution of Val for Ile in this position of the transmembrane region will destabilize the formation of active HER2 dimers mediated by the N-terminal dimerization motif and lead to reduced receptor activation and tyrosine kinase activity. However, the presence of the Val allele could reinforce the stabilization of the receptor’s active state, which results in augmentation of autophosphorylation, hyper-active tyrosine kinase, and cellular proliferation [59]. Bocharov and colleagues researched the spatial structure of the dimeric transmembrane domain of the HER2 protein. They found that the Ile655Val variant can excessively stabilize the ErbB2 active dimeric state due to substituting the bulk side chain of Ile with the smaller Val, thus allowing tighter TM helix packing [99]. In another experiment, Tanaka et al. assessed the role of amino acid substitutions in the conformational stability of human lysozyme protein via thermodynamic analysis at high temperature and very low pH. They showed that in constructed isoleucine to valine mutants, the strength of mutant proteins was reduced compared to that of the wild-type protein [100].

Advertisement

5. Association between HER2Ile655Val single nucleotide polymorphism and early-onset breast cancer susceptibility

Prior studies independently found a correlation between the high presence of the Val allele in the codon 655 of the HER2 gene and the onset of breast cancer [101, 102, 103, 104]. Additionally, Millikan et al. 2003 and Tommasi et al. 2007 reported a strong association between the variant allele 655Val and breast cancer in younger women when combined with family history [105, 106]. However, other published data reveal the opposite results, with no significant correlation between the HER2Ile655Val genotype and the risk of early-onset breast cancer in patients 40 to 50 years [63, 90, 107, 108, 109].

We conducted the meta-analysis, which collected 17 age-stratified articles with a cut-off age value from 40 to 55 years old (46.53 ± 3.84). We found that in young women, HER2 codon 655 polymorphism was strongly and significantly associated with breast cancer in all genetic models (additive, dominant, and recessive), which was in contrast to the results from a subgroup of older women (Data not shown).

Subgroup meta-analysis in the breast cancer population was utilized to investigate the association between HER2Ile655Val SNP and the age at onset of breast cancer, calculating adjusted RRs comparing older and younger participants in the breast cancer population (Figure 3). There was a significant 17% increase in the risk of early onset of breast cancer in patients who were Val carriers (Ile/Val and Val/Val) (dominant model, RR 0.83, 95% CI 0.72 to 0.97; I2 = 36.5%; n = 14). Meanwhile, no significant association of HER2Ile655Val SNP polymorphism with the age of onset was found in the subgroup of breast cancer women under an additive model (additive, RR 0.87, 95% CI 0.75–1.01, I2 = 39.8%; n = 10) and a recessive model (RR 0.96, 95% CI 0.73 to 1.26, I2 = 0.0%; n = 9). There was no publication bias in the studies (Begg’s funnel plot was symmetric; additive model, Egger’s test t = −2.02, P for bias = 0.078, n = 10; dominant model, Egger’s test t = −1.91, P for bias = 0.08, n = 14; recessive model, Egger’s test t = −2.27, P for bias = 0.057, n = 9). Furthermore, subgroup meta-analysis of the control population indicated no significant association between HER2Ile655Val SNP and the age of participants was found in control women under all genetic models (additive, RR 0.94, 95% CI 0.75 to 1.18; I2 = 28.1%; n = 6; dominant, RR 0.94, 95% CI 0.83 to 1.07; I2 = 0.0%; n = 9, and recessive, RR 1.19, 95% CI 0.70 to 2.02; I2 = 2.0%; n = 3) (Data not shown). In the breast cancer population, the dominant model of HER2Ile655Val SNP was shown to be significantly associated with younger age. Therefore, the high presence of the Val allele in codon 655 of the HER2 gene might explain the increasing frequency of younger age onset of breast cancer.

Figure 3.

HER2Ile655Val SNP is associated with an increased risk of early-onset breast cancer (modified from Nguyen Thanh et al. 2021) [98]. (A) Forest plot for the association between HER2Ile655Val SNP and an increased risk of early-onset breast cancer; (B) Funnel plot evaluating for publication bias among studies included in the meta-analysis.

Molecular mechanisms of the early onset state have been studied in certain types of cancer. Several candidate genes and signaling pathways have been found in the early onset of colorectal cancer. REG1A, CK20, and MAP3K8 gene expression were related to early-onset colorectal cancer formation [110]. Using PPI network analysis, Zhao and colleagues suggested that early-onset colorectal cancer is associated with vascular smooth muscle contraction signaling pathways. They also identified seven hub genes, namely, ACTA2, ACTG2, MYH11, CALD1, MYL9, TPM2, and LMOD1, along with this signaling pathway [111]. Recently, using weighted gene co-expression network analysis and other analysis methods, Mo et al. identified seven genes (SPARC, DCN, FBN1, WWTR1, TAGLN, DDX28, and CSDC2) associated with the development and prognosis of early-onset colorectal cancer. These genes may serve as novel biomarkers for diagnosing early-onset colorectal cancer [112]. In prostate cancer, a study conducted by Weischenfeldt et al. found the genomic alteration landscapes of early-onset prostate cancer compared to older-onset cancer. They discovered that early-onset prostate cancer possesses a higher frequency of balanced structural rearrangements, with a specific abundance of androgen-regulated ETS gene fusions, and concluded that ETS fusion genes are signs of early-onset prostate cancer [113]. Furthermore, Gerhauser et al. demonstrated the role of androgen receptor-driven rearrangements, an early APOBEC-driven mutational mechanism, and ESRP1 gene duplication that contributed to the pathogenesis seen in early-onset prostate cancer [114]. Nevertheless, the molecular mechanism involved in the pathogenesis of early-onset breast cancer is, to date, poorly understood and needs to be studied further.

Advertisement

6. Conclusion

HER2 was involved in the development and progression of mammary carcinogenesis, including breast cancer. HER2-targeted therapies have significantly enhanced the clinical outcome for HER2-positive breast cancer patients. HER2Ile655Val single nucleotide polymorphism associate with an increased risk of breast cancer. In addition, HER2Ile655Val SNP might be considered as a susceptibility factor for early-onset breast cancer. Further molecular studies are required to reveal the mechanism of this correlation.

References

  1. 1. Zahmatkesh B, Keramat A, Alavi N, Khosravi A, Kousha A, Motlagh AG, Darman M, Partovipour E, Chaman R: Breast cancer trend in Iran from 2000 to 2009 and prediction till 2020 using a trend analysis method. Asian Pacific Journal of Cancer Prevention 2016, 17(3):1493-1498.
  2. 2. Momenimovahed Z, Salehiniya H: Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer: Targets and Therapy 2019, 11:151.
  3. 3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2018, 68(6):394-424.
  4. 4. Jenkins C, Minh LN, Anh TT, Ngan TT, Tuan NT, Giang KB, Hoat LN, Lohfeld L, Donnelly M, Van Minh H et al: Breast cancer services in Vietnam: a scoping review. Global health action 2018, 11(1):1435344.
  5. 5. Siegel RL, Miller KD, Jemal A: Cancer statistics, 2020. CA: A Cancer Journal for Clinicians 2020, 70(1):7-30.
  6. 6. Dobi Á, Kelemen G, Kaizer L, Weiczner R, Thurzó L, Kahán Z: Breast cancer under 40 years of age: increasing number and worse prognosis. Pathology & Oncology Research 2011, 17(2):425-428.
  7. 7. Zubor P, Vojvodova A, Danko J, Kajo K, Szunyogh N, Lasabova Z, Biringer K, Visnovsky J, Dokus K, Galajda P: HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia. Neoplasma 2006, 53(1):49.
  8. 8. Bouchardy C, Fioretta G, Verkooijen H, Vlastos G, Schaefer P, Delaloye J, Neyroud-Caspar I, Majno SB, Wespi Y, Forni M: Recent increase of breast cancer incidence among women under the age of forty. British journal of cancer 2007, 96(11):1743-1746.
  9. 9. Yarden Y, Sliwkowski MX: Untangling the ErbB signalling network. Nature reviews Molecular cell biology 2001, 2(2):127-137.
  10. 10. Friedlander E, Barok M, Szollosi J, Vereb G: ErbB-directed immunotherapy: Antibodies in current practice and promising new agents (vol 116, pg 126, 2008). Immunology Letters 2009, 124(1):55-56.
  11. 11. Tai W, Mahato R, Cheng K: The role of HER2 in cancer therapy and targeted drug delivery. Journal of controlled release 2010, 146(3):264-275.
  12. 12. Incorvati JA, Shah S, Mu Y, Lu J: Targeted therapy for HER2 positive breast cancer. Journal of hematology & oncology 2013, 6(1):38.
  13. 13. Sidaway P: HER2-targeted agents overcome resistance. Nature reviews Clinical oncology 2020, 17(3):133.
  14. 14. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L: Treatment of HER2-positive breast cancer: current status and future perspectives. Nature reviews Clinical oncology 2012, 9(1):16-32.
  15. 15. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, De Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer cell 2004, 5(4):317-328.
  16. 16. Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G: Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. Journal of clinical oncology 2005, 23(11):2534-2543.
  17. 17. Nahta R, Yu D, Hung M-C, Hortobagyi GN, Esteva FJ: Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nature clinical practice Oncology 2006, 3(5):269-280.
  18. 18. Xie D, Shu XO, Deng Z, Wen WQ, Creek KE, Dai Q, Gao YT, Jin F, Zheng W: Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. Journal of the National Cancer Institute 2000, 92(5):412-417.
  19. 19. Montgomery KG, Gertig DM, Baxter SW, Milne RL, Dite GS, McCredie MR, Giles GG, Southey MC, Hopper JL, Campbell IG: The HER2 I655V polymorphism and risk of breast cancer in women < age 40 years. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2003, 12(10):1109-1111.
  20. 20. Lee S-C, Hou M-F, Hsieh P-C, Wu S-H, Hou LA, Ma H, Tsai S-M, Tsai L-Y: A case–control study of the HER2 Ile655Val polymorphism and risk of breast cancer in Taiwan. Clinical biochemistry 2008, 41(3):121-125.
  21. 21. Naidu R, Yip C, Taib NA: Polymorphisms of HER2 Ile655Val and cyclin D1 (CCND1) G870A are not associated with breast cancer risk but polymorphic allele of HER2 is associated with nodal metastases. Neoplasma 2008, 55(2):87-95.
  22. 22. Kara N, Karakus N, Ulusoy AN, Ozaslan C, Gungor B, Bagci H: P53 codon 72 and HER2 codon 655 polymorphisms in Turkish breast cancer patients. DNA and cell biology 2010, 29(7):387-392.
  23. 23. An HJ, Kim NK, Oh D, Kim SH, Park MJ, Jung MY, Kang H, Kim SG, Lee KP, Lee KS: Her2 genotype and breast cancer progression in Korean women. Pathology international 2005, 55(2):48-52.
  24. 24. Zubor P, Vojvodova A, Danko J, Kajo K, Szunyogh N, Lasabova Z, Biringer K, Visnovsky J, Dokus K, Galajda P et al: HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia. Neoplasma 2006, 53(1):49-55.
  25. 25. Muleris M, Almeida A, Malfoy B, Dutrillaux B. Assignment of v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) to human chromosome band 17q21. 1 by in situ hybridization. Cytogenetic and Genome Research 1997, 76(1/2):34.
  26. 26. Saini KS, Azim Jr HA, Metzger-Filho O, Loi S, Sotiriou C, de Azambuja E, Piccart M: Beyond trastuzumab: new treatment options for HER2-positive breast cancer. The Breast 2011, 20:S20-S27.
  27. 27. Piechocki MP, Yoo GH, Dibbley SK, Lonardo F: Breast cancer expressing the activated HER2/neu is sensitive to gefitinib in vitro and in vivo and acquires resistance through a novel point mutation in the HER2/neu. Cancer research 2007, 67(14):6825-6843.
  28. 28. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN: Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clinical medicine & research 2009, 7(1-2):4-13.
  29. 29. Iqbal N, Iqbal N: Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Molecular biology international 2014, 2014.
  30. 30. Knutson KL, Clynes R, Shreeder B, Yeramian P, Kemp KP, Ballman K, Tenner KS, Erskine CL, Norton N, Northfelt D: Improved survival of HER2+ breast cancer patients treated with trastuzumab and chemotherapy is associated with host antibody immunity against the HER2 intracellular domain. Cancer research 2016, 76(13):3702-3710.
  31. 31. Lv Q, Meng Z, Yu Y, Jiang F, Guan D, Liang C, Zhou J, Lu A, Zhang G: Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer. International journal of molecular sciences 2016, 17(12):49.
  32. 32. Di Modica M, Tagliabue E, Triulzi T: Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host. Disease markers 2017, 2017:7849108.
  33. 33. Krishnamurti U, Silverman JF: HER2 in breast cancer: a review and update. Advances in anatomic pathology 2014, 21(2):100-107.
  34. 34. Figueroa-Magalhaes MC, Jelovac D, Connolly R, Wolff AC: Treatment of HER2-positive breast cancer. Breast (Edinburgh, Scotland) 2014, 23(2):128-136.
  35. 35. Varga Z, Noske A, Ramach C, Padberg B, Moch H: Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study. BMC cancer 2013, 13(1):615.
  36. 36. Ellis C, Dyson M, Stephenson T, Maltby E: HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques. Journal of clinical pathology 2005, 58(7):710-714.
  37. 37. Parkes E, McKenna S, McAleer J, Clarke J, Clayton A, James C: HER2 as a prognostic factor in metastatic breast cancer treated with taxanes. Journal of Clinical Oncology 2010, 28(15_supply):1150-1150.
  38. 38. Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, McNally V, Ross G, Kiermaier A, Cortés J: Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab-and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Research 2014, 16(4):R73.
  39. 39. Mendes D, Alves C, Afonso N, Cardoso F, Passos-Coelho JL, Costa L, Andrade S, Batel-Marques F: The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer–a systematic review. Breast Cancer Research 2015, 17(1):140.
  40. 40. Allred DC, Clark GM, Molina R, Tandon AK, Schnitt SJ, Gilchrist KW, Osborne CK, Tormey DC, McGuire WL: Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Human pathology 1992, 23(9):974-979.
  41. 41. Pengfei S, Cheng C, Yufeng Y: Correlation Between HER-2 Gene Amplification or Protein Expression and Clinical Pathological Features of Breast Cancer. Cancer Biotherapy and Radiopharmaceuticals 2019, 34(1):42-46.
  42. 42. Aman NA, Doukoure B, Koffi KD, Koui BS, Traore ZC, Kouyate M, Effi AB: HER2 overexpression and correlation with other significant clinicopathologic parameters in Ivorian breast cancer women. BMC clinical pathology 2019, 19:1.
  43. 43. Iqbal N, Iqbal N: Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Molecular biology international 2014, 2014:852748.
  44. 44. Parkes E, McKenna SM, McAleer JJ, Clarke J, Clayton AJ, James CR: HER2 as a prognostic factor in metastatic breast cancer treated with taxanes. Journal of Clinical Oncology 2010, 28(15_supply):1150-1150.
  45. 45. Shokouh TZ, Ezatollah A, Barand P: Interrelationships Between Ki67, HER2/neu, p53, ER, and PR Status and Their Associations With Tumor Grade and Lymph Node Involvement in Breast Carcinoma Subtypes: Retrospective-Observational Analytical Study. Medicine 2015, 94(32):e1359-e1359.
  46. 46. Yokomizo A, Koga H, Kinukawa N, Tsukamoto T, Hirao Y, Akaza H, Mori M, Naito S: Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility. The Prostate 2005, 62(1):49-53.
  47. 47. Chen W, Yang H, Tang WR, Feng SJ, Wei YL: Updated meta-analysis on HER2 polymorphisms and risk of breast cancer: evidence from 32 studies. Asian Pacific journal of cancer prevention : APJCP 2014, 15(22):9643-9647.
  48. 48. Liang X, Zhang Y-j, Liu B, Ni Q, Jin M-j, Ma X-y, Yao K-y, Li Q-l: Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer. Chinese journal of medical genetics 2009, 26:302-305.
  49. 49. Xin DJ, Shen GD, Song J: Single nucleotide polymorphisms of HER2 related to osteosarcoma susceptibility. Int J Clin Exp Pathol 2015, 8(8):9494-9499.
  50. 50. Kuraoka K, Matsumura S, Hamai Y, Nakachi K, Imai K, Matsusaki K, Oue N, Ito R, Nakayama H, Yasui W: A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer. Int J Cancer 2003, 107(4):593-596.
  51. 51. Kruszyna L, Lianeri M, Roszak A, Jagodzinski PP: HER2 codon 655 polymorphism is associated with advanced uterine cervical carcinoma. Clin Biochem 2010, 43(6):545-548.
  52. 52. Zubor, Karol Kajob AS, Norbert Szunyogha, Silvester Galoa, Carlos A. Dussanad, Gabriel Minarikc, Jozef Visnovskya and Jan Danko: Human-epithelial-growth-factor-receptor-2Ile655Val-polymorphism-and-risk-of-breast-fibroadenoma European Journal of Cancer Prevention 2008, 17(1):33-38.
  53. 53. Ozturk O, Canbay E, Kahraman OT, Fatih Seyhan M, Aydogan F, Celik V, Uras C: HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer. Molecular biology reports 2013, 40(2):1813-1818.
  54. 54. Riaz SK, Rashid MM, Kayani MA, Malik MFA: Role of HER-2 Ile655Val Polymorphism as Universal Cancer Susceptibility Marker among Different Cancers. Archives of Iranian medicine 2016, 19(6):430 -438.
  55. 55. Frank B, Hemminki K, Wirtenberger M, Bermejo JL, Bugert P, Klaes R, Schmutzler RK, Wappenschmidt B, Bartram CR, Burwinkel B: The rare ERBB2 variant Ile654Val is associated with an increased familial breast cancer risk. Carcinogenesis 2005, 26(3):643-647.
  56. 56. Krishna BM, Chaudhary S, Panda AK, Mishra DR, Mishra SK: Her2 Ile 655 Val polymorphism and its association with breast cancer risk: an updated meta-analysis of case-control studies. Scientific reports 2018, 8(1):1-19.
  57. 57. Ameyaw M-M, Tayeb M, Thornton N, Folayan G, Tariq M, Mobarek A, Evans DP, Ofori-Adjei D, McLeod HL: Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer. Journal of human genetics 2002, 47(4):172-175.
  58. 58. Papewalis J, Nikitin A, Rajewsky MF: G to A polymorphism at amino acid codon 655 of the human erbB-2/HER2 gene. Nucleic acids research 1991, 19(19):5452.
  59. 59. Fleishman SJ SJ, Ben-Tal N.: A putative molecular-activation switch in the transmembrane domain of erbB2. Proceedings of the National Academy of Sciences (PNAS) 2002, 99(25):15937-15940.
  60. 60. AbdRaboh NR, Shehata HH, Ahmed MB, Bayoumi FA: HER1 R497K and HER2 I655V polymorphisms are linked to development of breast cancer. Disease markers 2013, 34(6):407-417.
  61. 61. Akisik E, Dalay N: Estrogen receptor codon 594 and HER2 codon 655 polymorphisms and breast cancer risk. Experimental and molecular pathology 2004, 76(3):260-263.
  62. 62. Al-Janabi AM, Algenabi AHA, Kamoona TH, Alkhafaji SM: Association of HER2 [ILe655Val] gene polymorphism and Breast Cancer Risk in Iraqi females Population. International Journal of Advanced Research 2015, 3(12):1483 – 1489.
  63. 63. Baxter SW, Campbell IG: Re: Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. Journal of the National Cancer Institute 2001, 93(7):557-559.
  64. 64. Benusiglio PR, Lesueur F, Luccarini C, Conroy DM, Shah M, Easton DF, Day NE, Dunning AM, Pharoah PD, Ponder BA: Common ERBB2 polymorphisms and risk of breast cancer in a white British population: a case-control study. Breast cancer research : BCR 2005, 7(2):R204-R209.
  65. 65. Cox DG, Hankinson SE, Hunter DJ: The erbB2/HER2/neu receptor polymorphism Ile655Val and breast cancer risk. Pharmacogenetics and genomics 2005, 15(7):447-450.
  66. 66. de Almeida FC, Banin Hirata BK, Ariza CB, Losi Guembarovski R, de Oliveira KB, Suzuki KM, Guembarovski AL, Oda JMM, Vitiello GAF, Watanabe MAE: HER2 Ile655Val polymorphism is negatively associated with breast cancer susceptibility. Journal of clinical laboratory analysis 2018, 32(6):e22406.
  67. 67. Han X, Diao L, Xu Y, Xue W, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B et al: Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology 2014, 25(6):1158-1164.
  68. 68. Hishida A, Hamajima N, Iwata H, Matsuo K, Hirose K, Emi N, Tajima K: Re: Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. Journal of the National Cancer Institute 2002, 94(23):1807-1808.
  69. 69. Kalemi TG, Lambropoulos AF, Gueorguiev M, Chrisafi S, Papazisis KT, Kotsis A: The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece. Cancer letters 2005, 222(1):57-65.
  70. 70. Kallel I, Kharrat N, Al-fadhly S, Rebai M, Khabir A, Boudawara TS, Rebai A: HER2 polymorphisms and breast cancer in Tunisian women. Genetic testing and molecular biomarkers 2010, 14(1):29-35.
  71. 71. Kamali-Sarvestani E, Talei AR, Merat A: Ile to Val polymorphism at codon 655 of HER-2 gene and breast cancer risk in Iranian women. Cancer letters 2004, 215(1):83-87.
  72. 72. Kara N, Karakus N, Ulusoy AN, Ozaslan C, Gungor B, Bagci H: P53 codon 72 and HER2 codon 655 polymorphisms in Turkish breast cancer patients. DNA and cell biology 2010, 29(7):387-392.
  73. 73. Keshava C, McCanlies EC, Keshava N, Wolff MS, Weston A: Distribution of HER2(V655) genotypes in breast cancer cases and controls in the United States. Cancer letters 2001, 173(1):37-41.
  74. 74. Lemieux J, Diorio C, Cote MA, Provencher L, Barabe F, Jacob S, St-Pierre C, Demers E, Tremblay-Lemay R, Nadeau-Larochelle C et al: Alcohol and HER2 polymorphisms as risk factor for cardiotoxicity in breast cancer treated with trastuzumab. Anticancer research 2013, 33(6):2569-2576.
  75. 75. Lee SC, Hou MF, Hsieh PC, Wu SH, Hou LA, Ma H, Tsai SM, Tsai LY: A case-control study of the HER2 Ile655Val polymorphism and risk of breast cancer in Taiwan. Clinical biochemistry 2008, 41(3):121-125.
  76. 76. Millikan R, Eaton A, Worley K, Biscocho L, Hodgson E, Huang WY, Geradts J, Iacocca M, Cowan D, Conway K et al: HER2 codon 655 polymorphism and risk of breast cancer in African Americans and whites. Breast cancer research and treatment 2003, 79(3):355-364.
  77. 77. Mutluhan H, Akbas E, Erdogan NE, Soylemez F, Senli MS, Polat A, Helvaci I, Seyrek E: The influence of HER2 genotypes as molecular markers on breast cancer outcome. DNA and cell biology 2008, 27(10):575-579.
  78. 78. Naidu R, Yip CH, Taib NA: Polymorphisms of HER2 Ile655Val and cyclin D1 (CCND1) G870A are not associated with breast cancer risk but polymorphic allele of HER2 is associated with nodal metastases. Neoplasma 2008, 55(2):87-95.
  79. 79. Nelson SE, Gould MN, Hampton JM, Trentham-Dietz A: A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer. Breast cancer research : BCR 2005, 7(3):R357-R364.
  80. 80. Papadopoulou E, Simopoulos K, Tripsianis G, Tentes I, Anagnostopoulos K, Sivridis E, Galazios G, Kortsaris A: Allelic imbalance of HER-2 codon 655 polymorphism among different religious/ethnic populations of northern Greece and its association with the development and the malignant phenotype of breast cancer. Neoplasma 2007, 54(5):365-373.
  81. 81. Parvin S, Islam MS, Al-Mamun MM, Islam MS, Ahmed MU, Kabir ER, Hasnat A: Association of BRCA1, BRCA2, RAD51, and HER2 gene polymorphisms with the breast cancer risk in the Bangladeshi population. Breast cancer 2017, 24(2):229-237.
  82. 82. Pinto D, Vasconcelos A, Costa S, Pereira D, Rodrigues H, Lopes C, Medeiros R: HER2 polymorphism and breast cancer risk in Portugal. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation 2004, 13(3):177-181.
  83. 83. Qu S, Cai Q, Gao YT, Lu W, Cai H, Su Y, Wang SE, Shu XO, Zheng W: ERBB2 genetic polymorphism and breast cancer risk in Chinese women: a population-based case-control study. Breast cancer research and treatment 2008, 110(1):169-176.
  84. 84. Rajkumar T, Samson M, Rama R, Sridevi V, Mahji U, Swaminathan R, Nancy NK: TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy. Breast cancer research and treatment 2008, 112(1):81-87.
  85. 85. Roca L, Dieras V, Roche H, Lappartient E, Kerbrat P, Cany L, Chieze S, Canon JL, Spielmann M, Penault-Llorca F et al: Correlation of HER2, FCGR2A, and FCGR3A gene polymorphisms with trastuzumab related cardiac toxicity and efficacy in a subgroup of patients from UNICANCER-PACS 04 trial. Breast cancer research and treatment 2013, 139(3):789-800.
  86. 86. Sezgin E, Sahin FI, Yagmurdur MC, Demirhan B: HER-2/neu gene codon 655 (Ile/Val) polymorphism in breast carcinoma patients. Genetic testing and molecular biomarkers 2011, 15(3):143-146.
  87. 87. Siddig A, Mohamed AO, Kamal H, Awad S, Hassan AH, Zilahi E, Al-Haj M, Bernsen R, Adem A: HER-2/neu Ile655Val polymorphism and the risk of breast cancer. Annals of the New York Academy of Sciences 2008, 1138:84-94.
  88. 88. Tommasi S, Fedele V, Lacalamita R, Bruno M, Schittulli F, Ginzinger D, Scott G, Eppenberger-Castori S, Calistri D, Casadei S et al: 655Val and 1170Pro ERBB2 SNPs in familial breast cancer risk and BRCA1 alterations. Cellular oncology : the official journal of the International Society for Cellular Oncology 2007, 29(3):241-248.
  89. 89. Wang-Gohrke S, Chang-Claude J: Re: Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. Journal of the National Cancer Institute 2001, 93(21):1657-1659.
  90. 90. Watrowski R, Castillo-Tong DC, Wolf A, Schuster E, Fischer MB, Speiser P, Zeillinger R: HER2 Codon 655 (Ile/Val) Polymorphism and Breast Cancer in Austrian Women. Anticancer research 2015, 35(12):6667-6670.
  91. 91. Zhang M, Guo LL, Cheng Z, Liu RY, Lu Y, Qian Q, Lei Z, Zhang HT: A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER(+), PR(+), ER(+)PR(+) and HER2(−) expression in women. Oncology letters 2011, 2(4):653-658.
  92. 92. Zubor P, Kajo K, Stanclova A, Szunyogh N, Galo S, Dussan CA, Minarik G, Visnovsky J, Danko J: Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of breast fibroadenoma. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation 2008, 17(1):33-38.
  93. 93. Tao W, Wang C, Han R, Jiang H: HER2 codon 655 polymorphism and breast cancer risk: a meta-analysis. Breast cancer research and treatment 2009, 114(2):371-376.
  94. 94. Lu S, Wang Z, Liu H, Hao X: HER2 Ile655Val polymorphism contributes to breast cancer risk: evidence from 27 case-control studies. Breast Cancer Res Treat 2010, 124(3):771-778.
  95. 95. Wang H, Liu L, Lang Z, Guo S, Gong H, Guan H, Zhang J, Liu B: Polymorphisms of ERBB2 and breast cancer risk: a meta-analysis of 26 studies involving 35,088 subjects. Journal of surgical oncology 2013, 108(6):337-341.
  96. 96. Krishna BM, Chaudhary S, Panda AK, Mishra DR, Mishra SK: Her2 (Ile)655(Val) polymorphism and its association with breast cancer risk: an updated meta-analysis of case-control studies. Sci Rep 2018, 8(1):7427.
  97. 97. Ma Y, Yang J, Zhang P, Liu Z, Yang Z, Qin H: Lack of association between HER2 codon 655 polymorphism and breast cancer susceptibility: meta-analysis of 22 studies involving 19,341 subjects. Breast cancer research and treatment 2011, 125(1):237-241.
  98. 98. Nguyen Thanh T, Nguyen Tran BS, Hoang Thi AP, Tran Binh T, Ba Nguyen T, Le Minh T, Nguyen Vu QH, Dang Cong T: HER2Ile655Val Single Nucleotide Polymorphism Associated with Early-Onset Breast Cancer Susceptibility: A Systematic Review and Meta-Analysis. Asian Pacific journal of cancer prevention : APJCP 2021, 22(1):11-18.
  99. 99. Bocharov EV, Mineev KS, Volynsky PE, Ermolyuk YS, Tkach EN, Sobol AG, Chupin VV, Kirpichnikov MP, Efremov RG, Arseniev AS: Spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 presumably corresponding to the receptor active state. J Biol Chem 2008, 283(11):6950-6956.
  100. 100. Takano K OK, Kaneda H, Yamagata Y, Fujii S, Kanaya E, Kikuchi M, Oobatake M, Yutani K: Hydrophobic Residues to the Stability of Human Lysozyme Calorimetric Studies and X-ray Structural Analysis of the Five Isoleucine to Valine Mutants. J Mol Biol 1995, 254:62 - 76.
  101. 101. Papadopoulou E, Tripsianis G, Tentes I, Anagnostopoulos K, Sivridis E, Galazios G, Kortsaris A: Allelic imbalance of HER-2 codon 655 polymorphism among different religious/ethnic populations of northern Greece and its association with the development and the malignant phenotype of breast cancer. Neoplasma 2007, 54(6):365 - 373.
  102. 102. Xie Dawen X-OS, Zonglin Deng, Wan-Qing Wen, Kim E. Creek, Qi Dai, Yu-Tang Gao, Fan Jin, Wei Zheng: Population-Based, Case–Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk. Journal of the National Cancer Institute, 2000, 92(5):412 - 417.
  103. 103. Karen G. Montgomery DMG, Simon W. Baxter, Roger L. Milne, Gillian S. Dite, Margaret R.E. McCredie, Graham G. Giles, Melissa C. Southey, John L. Hopper, Ian G. Campbell: The HER2 I655V Polymorphism and Risk of Breast Cancer in Women < Age 40 Years. Cancer Epidemiology, Biomarkers & Prevention 2003, 12:1109-1111.
  104. 104. Joni L. Rutter, Nilanjan Chatterjee fSW, f and Jeffrey Struewing: The HER2 I655V polymorphism and Breast cancer risk in Ashkenazim. Epidemiology 2003, 14(6): 694-700.
  105. 105. Robert Millikan AE, Kendra Worley, Lorna Biscocho, Elizabeth Hodgson, Wen-Yi Huang, Joseph Geradts, Mary Iacocca, David Cowan, Kathleen Conway, Dressler L: HER2 codon 655 polymorphism and risk of breast cancer in African American and whites. Breast Cancer Research and Treatment 2003, 79:355 - 364.
  106. 106. Tommasi Vita Fedele, Michele Bruno, Francesco Schittulli, David Ginzinger, Gery Scott, Serenella Eppenberger-Castori, Daniele Calistri, Silvia Casadei, Ian Seymour, Salvatore Longo, Gianluigi Giannelli, Brunella Pilato, Giovanni Simone, Christopher C. Benz and Angelo Paradiso: 655Val-and-1170Pro-ERBB2-SNPs-in-familial-breast-cancer-risk-and-BRCA1-alterations. Cellular Oncology 2007, 29:241 - 248.
  107. 107. Nurten Kara NK, Ali Naki Ulusoy, Cihangir Ozaslan, Bulent Gungor, and Hasan Bagci: P53-codon-72-and-HER2-codon-655-polymorphisms-in-Turkish-breast-cancer-patients. DNA and cell biology 2010, 29(7):387-392.
  108. 108. An Hee Jung, Haeyoun Kang, Nam Keun Kim SGK: Her2 genotype and breast cancer progression in Korean women. Pathology International 2005, 55:48 - 52.
  109. 109. Chan KY, Cheung AN, Yip SP, Ko HH, Lai TW, Khoo US: Population-based case-control study of HER2 genetic polymorphism and breast cancer risk. Journal of the National Cancer Institute 2002, 94(20):1581-1582.
  110. 110. Tezcan G, Tunca B, Ak S, Cecener G, Egeli U: Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer. World J Gastrointest Oncol 2016, 8(1):83-98.
  111. 111. Zhao B, Baloch Z, Ma Y, Wan Z, Huo Y, Li F, Zhao Y: Identification of Potential Key Genes and Pathways in Early-Onset Colorectal Cancer Through Bioinformatics Analysis. Cancer Control 2019, 26(1):1073274819831260.
  112. 112. Mo X, Su Z, Yang B, Zeng Z, Lei S, Qiao H: Identification of key genes involved in the development and progression of early-onset colorectal cancer by co-expression network analysis. Oncol Lett 2020, 19(1):177-186.
  113. 113. Weischenfeldt J, Simon R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz HJ, Stehr H, Rausch T et al: Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 2013, 23(2):159-170.
  114. 114. Gerhauser C, Favero F, Risch T, Simon R, Feuerbach L, Assenov Y, Heckmann D, Sidiropoulos N, Waszak SM, Hubschmann D et al: Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories. Cancer Cell 2018, 34(6):996-1011 e1018.

Written By

Tung Nguyen-Thanh, Thong Ba Nguyen and Thuan Dang-Cong

Submitted: 14 June 2021 Reviewed: 15 July 2021 Published: 21 August 2021

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Continue reading from the same book

View All
Chapter 7 Human Genetic Polymorphisms Associated with Suscep...

By Necla Benlier, Nevhiz Gundogdu and Mehtap Ozkur

253 downloads

Chapter 8 Characterization, Comparative, and Phylogenetic An...

By Aloysius Brown, Orlex B. Yllano, Leilani D. Arce, ...

324 downloads

Chapter 9 Sex Determination

By Rakesh Choudhary, Subhash Chand, Tejveer Singh, Ra...

451 downloads