ORIGINAL ARTICLE
Characterisation of IGF-1 (rs7136446) and IL-6 (rs1800795) polymorphisms among breast cancer patients in western Algeria
1
Biology of Development and Differentiation Laboratory, Ahmed Ben Bella Oran 1 University, Oran, Algeria
2
Department of the Living and Environment, University of Sciences and Technology of Oran, Mohammed-Boudiaf, Oran, Algeria
3
Faculty of Medicine, Abdelhamid Ben Badis University Mostaganem, Mostaganem, Algeria
4
Pasteur Institute of Oran, Oran, Algeria
5
Department of Applied Molecular Genetics, University of Sciences and Technology of Oran, Mohammed-Boudiaf, Oran, Algeria
6
Department of Biology, Abdelhamid Ben Badis University Mostaganem, Mostaganem, Algeria
Submission date: 2023-12-27
Final revision date: 2024-02-29
Acceptance date: 2024-06-05
Publication date: 2024-10-16
Corresponding author
Fatima Zohraa Boussouf
Fatima Zohraa Boussouf Biology of Development and Differentiation Laboratory Ahmed Ben Bella Oran 1 University Oran, Algeria
Fatima Zohraa Boussouf Biology of Development and Differentiation Laboratory Ahmed Ben Bella Oran 1 University Oran, Algeria
Pol J Pathol 2024;75(3):205-214
KEYWORDS
breast cancer (BC)interleukin 6 (IL-6)insulin-like growth factor 1 (IGF-1)human epidermal growth factor receptor 2 (HER-2)single nucleotide polymorphisms (SNPs)western Algeria
TOPICS
ABSTRACT
Breast cancer (BC) is the most frequently diagnosed cancer among women worldwide, including Algeria. Certain single nucleotide polymorphisms (SNPs) have been linked to higher risk of BC. Several studies have been performed on the insulin- like growth factor 1 (IGF-1) T > C (rs7136446) and the interleukin 6 (IL-6) 174 G > C (rs1800795) SNPs to explore their role in BC. The aim of this study is to investigate the association between the 2 SNPs, IL-6 (rs1800795) and IGF-1 (rs7136446) with BC in the population of western Algeria.
This study was carried out for the first time among the Algerian population. This case-control study included 109 BC patients and 112 healthy controls. Genomic DNA was extracted from peripheral blood samples. DNA concentration was determined using the Qubit 2.0 fluorometer. The genotyping of selected SNPs was performed by real-time polymerase chain reaction followed by statistical analysis to assess genotypic frequencies and genetic association with BC.
The results showed that IGF-1 rs7136446 was positively associated with BC (p = 0.00001) and that the distribution of genotype frequencies of rs7136446 showed a statistically difference between human epidermal growth factor receptor 2 (HER-2) positive and HER-2 negative BC (p = 0.04), but this association did not last after the correction of Bonferroni. No association was found in genotype distribution of the IL-6 (rs1800795) among controls and BC patients or with clinicopathological parameters including HER-2 status in BC (p > 0.05).
In summary, our findings indicate that IGF-1 rs7136446 is associated with BC in our population of western Algeria.
This study was carried out for the first time among the Algerian population. This case-control study included 109 BC patients and 112 healthy controls. Genomic DNA was extracted from peripheral blood samples. DNA concentration was determined using the Qubit 2.0 fluorometer. The genotyping of selected SNPs was performed by real-time polymerase chain reaction followed by statistical analysis to assess genotypic frequencies and genetic association with BC.
The results showed that IGF-1 rs7136446 was positively associated with BC (p = 0.00001) and that the distribution of genotype frequencies of rs7136446 showed a statistically difference between human epidermal growth factor receptor 2 (HER-2) positive and HER-2 negative BC (p = 0.04), but this association did not last after the correction of Bonferroni. No association was found in genotype distribution of the IL-6 (rs1800795) among controls and BC patients or with clinicopathological parameters including HER-2 status in BC (p > 0.05).
In summary, our findings indicate that IGF-1 rs7136446 is associated with BC in our population of western Algeria.
REFERENCES (59)
2.
Denduluri SK, Idowu O, Wang Z, et al. Insulin-like growth factor (IGF) signalling in tumourigenesis and the development of cancer drug resistance. Genes Dis 2015; 2: 13-25.
3.
Yerushalmi R, Gelmon KA, Leung S, et al. Insulin-like growth factor receptor (IGF-1R) in breast cancer subtypes. Breast Cancer Res Treat 2012; 132: 131-142.
4.
Duggan C, Wang CY, Neuhouser ML, et al. Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer. Int J Cancer 2013; 132: 1191-1200.
5.
Camirand A, Lu Y, Pollak M. Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells. Med Sci Monit 2002; 8: Br521-526.
6.
Hartman ZC, Yang XY, Glass O, et al. HER2 overexpression elicits a proinflammatory IL-6 autocrine signalling loop that is critical for tumourigenesis. Cancer Res 2011; 71: 4380-4391.
7.
Christopoulos PFP, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Mol Cancer 2015; 14: 43.
8.
Sachdev D, Yee D. The IGF system and breast cancer. Endocr Relat Cancer 2001; 8: 197-209.
9.
Höppener JW, de Pagter-Holthuizen P, Geurts van Kessel AH, et al. The human gene encoding insulin-like growth factor I is located on chromosome 12 Hum. Genet 1985; 69: 157-160.
10.
Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin- like growth factor-I and prostate cancer risk: a prospective study. Science 1998; 279: 563-566.
11.
Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin- like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004; 363: 1346-1353.
12.
Rinaldi S, Cleveland R, Norat T, et al. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int J Cancer 2010; 126: 1702-715.
13.
Ma J, Pollak M, Giovannucci E, et al. A prospective study of plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3, and colorectal cancer risk among men. Growth Horm IGF Res 2000; 10: S28-29.
14.
Key TJ, Appleby PN, Reeves GK, Roddam AW. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11: 530-542.
15.
Kurmasheva RT, Houghton PJ. IGF-I mediated survival pathways in normal and malignant cells. Biochim Biophys Acta2 006; 1766: 1-22.
16.
Harrela M, Koistinen H, Kaprio J, et al. Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3. J Clin Invest 1996; 98: 2612-2615.
17.
Jernström H, Sandberg T, Bågeman E, et al. Insulin-like growth factor-1 (IGF1) genotype predicts breast volume after pregnancy and hormonal contraception and is associated with circulating IGF-1 levels: implications for risk of early-onset breast cancer in young women from hereditary breast cancer families. Br J Cancer 2005; 92: 857-866.
18.
Palles C, Johnson N, Coupland B, et al. Identification of genetic variants that influence circulating IGF1 levels: a targeted search strategy. Hum Mol Genet 2008; 17: 1457-1464.
19.
Al-Zahrani A, Sandhu MS, Luben RN, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet 2006; 15: 1-10.
20.
Verheus M, McKay JD, Kaaks R, et al. Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density. Breast Cancer Res Treat 2008; 112: 109-122.
21.
Byrne C, Colditz GA, Willett WC, Speizer FE, Pollak M, Hankinson SE. Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. Cancer Res 2000; 60: 3744-3748.
22.
Boyd NF, Stone J, Martin LJ, et al. The association of breast mitogens with mammographic densities. Br J Cancer 2002; 87: 876-882.
23.
Costa-Silva DR, da Conceição Barros-Oliveira M, Borges RS, et al. Insulin-like growth factor 1 gene polymorphism in women with breast cancer. Med Oncol 2017; 34: 59.
24.
Henningson M, Hietala M, Törngren T, Olsson H, Jernström H. IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early- onset breast cancer. Fam Cancer 2011; 10: 173-185.
25.
Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 2019; 51: 27-41.
26.
Zamarron BF, Chen W. Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci 2011; 7: 651-658.
27.
Rašková M, Lacina L, Kejík Z, et al. The role of IL-6 in cancer cell invasiveness and metastasis-overview and therapeutic opportunities. Cells 2022; 11: 3698.
28.
Terry CF, Loukaci V, Green FR. Cooperative influence of gene-tic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 2000; 275: 18138-18144.
29.
Saha A, Bairwa NK, Ranjan A, Gupta V, Bamezai R. Two novel somatic mutations in the human interleukin 6 promoter region in a patient with sporadic breast cancer. Eur J Immunogenet 2003; 30: 397-400.
30.
Dethlefsen C, Hojfeldt G, Hojman P. The role of intratumoural and systemic IL-6 in breast cancer Breast. Cancer Res Treat 2013; 138: 657-664.
31.
Shi J, Aronson KJ, Grundy A, et al. Polymorphisms of insulin-like growth Factor 1 pathway genes and breast cancer risk. Front 2016; 6: 136.
32.
Henningson M, Hietala M, Torngren T, Olsson H, Jernstrom H. IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer. Fam Cancer 2011; 10: 173-185.
33.
Muendlein A, Lang AH, Geller-Rhomberg S, et al. Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer. J Cancer Res Clin Oncol 2013; 139: 491-498.
34.
Winder T, Zhang W, Yang D, et al. Germline polymorphisms in genes involved in the IGF1 pathway predict efficacy of cetuximab in wild-type KRAS mCRC patients. Clin Cancer Res 2010; 16: 5591-5602.
35.
Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta 2007; 1773: 642-652.
36.
Bromberg J, Wang TC. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 2009; 15: 79-80.
37.
Kozlowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz MZ. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients Rocz Akad Med Bialymst 2003; 48: 82-84.
38.
Shibayama O, Yoshiuchi K, Inagaki M, et al. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy. Cancer Med 2014; 3: 702-709.
39.
Guo Y, Xu F, Lu T, Duan Z, Zhang Z. Interleukin-6 signalling pathway in targeted therapy for cancer. Cancer Treat Rev 2012; 38: 904-910. .
40.
Yu KD, Di GH, Fan L, Chen AX, Yang C, Shao ZM. Lack of an association between a functional polymorphism in the interleukin-6 gene promoter and breast cancer risk: a meta-analysis involving 25,703 subjects. Breast Cancer Res Treat 2010; 122: 483-488.
41.
Bouhniz OE, Zaied S, Naija L, et al. Association between HER2 and IL-6 genes polymorphisms and clinicopathological characteristics of breast cancer: significant role of genetic variability in specific breast cancer subtype. Clin Exp Med 2020; 20: 427-436.
42.
Balasubramanian SP, Azmy IA, Higham SE, et al. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review. BMC Cancer 2006; 6 : 188.
43.
Chérel M, Campion L, Bézieau S, et al. Molecular screening of interleukin-6 gene promoter and influence of 174G/C polymorphism on breast cancer. Cytokine 2009; 47: 214-223.
44.
DeMichele A, Martin AM, Mick R, et al. Interleukin-6-174G > C polymorphism is associated with improved outcome in high-risk breast cancer. Cancer Res 2003; 63: 8051-8056.
45.
Iacopetta B, Grieu F, Joseph D. The –174 G/C gene polymorphism in interleukin-6 is associated with an aggressive breast cancer phenotype. Br J Cancer 2004; 90: 419-422.
46.
Pooja S, Chaudhary P, Nayak LV, et al. Polymorphic variations in IL-1, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women. Cytokine 2012; 60: 122-128.
47.
Padala C, Puranam K, Shyamala N, et al. Genotypic and haplotype analysis of Interleukin-6 and -18 gene polymorphisms in association with clinicopathological factors in breast cancer. Cytokine 2022; 160: 156024.
48.
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition Nat Rev Mol Cell Biol 2014; 15: 178-196.
49.
Ricciardi M, Zanotto M, Malpeli G, et al. Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune modulatory properties in cancer cells. Br J Cancer 2015; 112: 1067- 1075.
50.
Madden KS, Szpunar MJ, Brown EB. Beta-adrenergic receptors (beta-AR) regulate VEGF and IL-6 production by divergent pathways in high beta-AR-expressing breast cancer cell lines. Breast Cancer Res Treat 2011; 130: 747-758.
51.
Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population Mol Cell 2012; 47: 570-584.
52.
DeMichele A, Gray R, Horn M, et al. Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with oestrogen receptor-positive, node-positive breast cancer. Cancer Res 2009; 69: 4184-4191.
53.
Abana CO, Bingham BS, Cho JH, et al. IL-6 variant is associated with metastasis in breast cancer patients. PLoS One 2017; 12: e0181725.
54.
Chavey C, Bibeau F, Gourgou-Bourgade S, et al. Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res 2007; 9: R15.
55.
Fontanini G, Campani D, Roncella M, et al. Expression of interleukin 6 (IL-6) correlates with oestrogen receptor in human breast carcinoma. Br J Cancer 1999; 80: 579-584.
56.
Chiu JJ, Sgagias MK, Cowan KH. Interleukin 6 acts as a paracrine growth factor in human mammary carcinoma cell lines. Clin Cancer Res1996; 2: 215-221.
57.
Selander KS, Li Li, Watson L, et al. Inhibition of gp130 signalling in breast cancer blocks constitutive activation of Stat3 and inhibits in vivo malignancy. Cancer Res 2004; 64: 6924-6933.
58.
Korobeinikova E, Ugenskiene R, Insodaite R, et al. Association of angiogenesis and inflammation-related gene functional polymorphisms with early-stage breast cancer prognosis. Oncol Lett 2020; 19: 3687-3700.
59.
Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell 2012; 47: 570-584.
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
