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 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2014

Open Access 01-12-2014 | Primary research

Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk

Authors: Yin Duan, Chi Pan, Jinan Shi, Hailong Chen, Suzhan Zhang

Published in: Cancer Cell International | Issue 1/2014

Login to get access

Abstract

Background

Interleukin-4(IL-4) is a critical inflammatory cytokine and has been involved in pathogenesis of cancer. To date, several studies have investigated the association between IL-4 intron 3 variable number of tandem repeats (VNTR) polymorphism and cancer risk in humans; however, the results remain controversial. We performed this meta-analysis to find a more conclusive association between this polymorphism and cancer risk.

Methods

Eight eligible case–control studies were identified through searching electronic databases, including 1583 cases and 1638 controls. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate the strength of the association.

Results

The results of overall analyses indicated that the variant RP2 allele was associated with a decreased cancer risk compared with the RP1 allele (RP2/RP2 vs. RP1/RP1, OR = 0.64, 95% CI = 0.44-0.94; RP2/RP2 vs. RP1/RP1 + RP1/RP2, OR = 0.75, 95% CI = 0.60-0.92; RP2 vs. RP1, OR = 0.72, 95% CI = 0.56-0.92). In subgroup analyses stratified by ethnicity, there was evidence in the Asian population for an association between this polymorphism and cancer risk (RP2/RP2 vs. RP1/RP1 + RP1/RP2, OR = 0.79, 95% CI = 0.63-0.99; RP2 vs. RP1, OR = 0.77, 95% CI = 0.61-0.97).

Conclusions

IL-4 intron 3 VNTR polymorphism could influence the risk of human cancer. Due to the limitations of this meta-analysis, further well-designed and functional researches should be performed to validate our results.
Appendix
Available only for authorised users
Literature
1.
Hoeijmakers JH: Genome maintenance mechanisms for preventing cancer. Nature. 2001, 411 (6835): 366-374. 10.1038/35077232.CrossRefPubMed
2.
Bredberg A: Cancer: more of polygenic disease and less of multiple mutations? A quantitative viewpoint. Cancer. 2011, 117 (3): 440-445. 10.1002/cncr.25440.CrossRefPubMed
3.
Wang S, Liu Z, Wang L, Zhang X: NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol. 2009, 6 (5): 327-334. 10.1038/cmi.2009.43.CrossRefPubMedCentralPubMed
4.
Kuper H, Adami HO, Trichopoulos D: Infections as a major preventable cause of human cancer. J Intern Med. 2000, 248 (3): 171-183. 10.1046/j.1365-2796.2000.00742.x.CrossRefPubMed
5.
Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, Oksenberg J, McNicholl J, Pociot F, Hardt C, D’Alfonso S: Cytokine gene polymorphism in human disease: on-line databases. Genes Immun. 1999, 1 (1): 3-19. 10.1038/sj.gene.6363645.CrossRefPubMed
6.
Olver S, Apte S, Baz A, Kienzle N: The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?. Tissue Antigens. 2007, 69 (4): 293-298. 10.1111/j.1399-0039.2007.00831.x.CrossRefPubMed
7.
Swain SL, Weinberg AD, English M, Huston G: IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990, 145 (11): 3796-3806.PubMed
8.
Toi M, Bicknell R, Harris AL: Inhibition of colon and breast carcinoma cell growth by interleukin-4. Cancer Res. 1992, 52 (2): 275-279.PubMed
9.
Yu SJ, Kim HS, Cho SW, Sohn J: IL-4 inhibits proliferation of renal carcinoma cells by increasing the expression of p21WAF1 and IRF-1. Exp Mol Med. 2004, 36 (4): 372-379. 10.1038/emm.2004.49.CrossRefPubMed
10.
Myers JN, Yasumura S, Suminami Y, Hirabayashi H, Lin W, Johnson JT, Lotze MT, Whiteside TL: Growth stimulation of human head and neck squamous cell carcinoma cell lines by interleukin 4. Clin Cancer Res. 1996, 2 (1): 127-135.PubMed
11.
Manchanda P, Sharma SC, Das SN: Differential regulation of IL-2 and IL-4 in patients with tobacco-related oral squamous cell carcinoma. Oral Dis. 2006, 12 (5): 455-462. 10.1111/j.1601-0825.2005.01220.x.CrossRefPubMed
12.
Agarwal A, Rani M, Saha GK, Valarmathi TM, Bahadur S, Mohanti BK, Das SN: Disregulated expression of the Th2 cytokine gene in patients with intraoral squamous cell carcinoma. Immunol Investig. 2003, 32 (1–2): 17-30. 10.1081/IMM-120019205.CrossRef
13.
Yamamoto T, Yoneda K, Ueta E, Hirota J, Osaki T: Serum cytokine levels in patients with oral mucous membrane disorders. J Oral Pathol Med. 1991, 20 (6): 275-279. 10.1111/j.1600-0714.1991.tb00927.x.CrossRefPubMed
14.
Liang J, Li Y, Liu X, Xu X, Zhao Y: Relationship between cytokine levels and clinical classification of gastric cancer. Asian Pac J Cancer Prev. 2011, 12 (7): 1803-1806.PubMed
15.
Goto T, Nishizono A, Fujioka T, Ikewaki J, Mifune K, Nasu M: Local secretory immunoglobulin A and postimmunization gastritis correlate with protection against Helicobacter pylori infection after oral vaccination of mice. Infect Immun. 1999, 67 (5): 2531-2539.PubMedCentralPubMed
16.
Serefoglou Z, Yapijakis C, Nkenke E, Vairaktaris E: Genetic association of cytokine DNA polymorphisms with head and neck cancer. Oral Oncol. 2008, 44 (12): 1093-1099. 10.1016/j.oraloncology.2008.02.012.CrossRefPubMed
17.
Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M, Borish L: Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy. 1995, 25 (Suppl 2): 74-78. 10.1111/j.1365-2222.1995.tb00428.x. discussion 95–76CrossRefPubMed
18.
19.
Nakashima H, Miyake K, Inoue Y, Shimizu S, Akahoshi M, Tanaka Y, Otsuka T, Harada M: Association between IL-4 genotype and IL-4 production in the Japanese population. Genes Immun. 2002, 3 (2): 107-109. 10.1038/sj.gene.6363830.CrossRefPubMed
20.
Breslow NE, Day NE: Statistical methods in cancer research. Volume II--The design and analysis of cohort studies.IARC Sci Publ 1987, (82):1–406.,
21.
Haber M: Exact significance levels of goodness-of-fit tests for the Hardy-Weinberg equilibrium. Hum Hered. 1981, 31 (3): 161-166. 10.1159/000153199.CrossRefPubMed
22.
23.
Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959, 22 (4): 719-748.PubMed
24.
DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials. 1986, 7 (3): 177-188. 10.1016/0197-2456(86)90046-2.CrossRefPubMed
25.
Sterne JA, Gavaghan D, Egger M: Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000, 53 (11): 1119-1129. 10.1016/S0895-4356(00)00242-0.CrossRefPubMed
26.
Tsai FJ, Chang CH, Chen CC, Hsia TC, Chen HY, Chen WC: Interleukin-4 gene intron-3 polymorphism is associated with transitional cell carcinoma of the urinary bladder. BJU Int. 2005, 95 (3): 432-435. 10.1111/j.1464-410X.2005.05315.x.CrossRefPubMed
27.
Tsai MH, Chen WC, Tsai CH, Hang LW, Tsai FJ: Interleukin-4 gene, but not the interleukin-1 beta gene polymorphism, is associated with oral cancer. J Clin Lab Anal. 2005, 19 (3): 93-98. 10.1002/jcla.20060.CrossRefPubMed
28.
Lai KC, Chen WC, Jeng LB, Li SY, Chou MC, Tsai FJ: Association of genetic polymorphisms of MK, IL-4, p16, p21, p53 genes and human gastric cancer in Taiwan. Eur J Surg Oncol. 2005, 31 (10): 1135-1140. 10.1016/j.ejso.2005.07.005.CrossRefPubMed
29.
Kesarwani P, Ahirwar DK, Mandhani A, Mittal RD: Association between −174 G/C promoter polymorphism of the interleukin-6 gene and progression of prostate cancer in North Indian population. DNA Cell Biol. 2008, 27 (9): 505-510. 10.1089/dna.2008.0742.CrossRefPubMed
30.
Konwar R, Chaudhary P, Kumar S, Mishra D, Chattopadhyay N, Bid HK: Breast cancer risk associated with polymorphisms of IL-1RN and IL-4 gene in Indian women. Oncol Res. 2009, 17 (8): 367-372. 10.3727/096504009788428442.CrossRefPubMed
31.
Shekari M, Kordi-Tamandani DM, MalekZadeh K, Sobti RC, Karimi S, Suri V: Effect of anti-inflammatory (IL-4, IL-10) cytokine genes in relation to risk of cervical carcinoma. Am J Clin Oncol. 2012, 35 (6): 514-519. 10.1097/COC.0b013e31822d9c12.CrossRefPubMed
32.
Yang CM, Chen HC, Hou YY, Lee MC, Liou HH, Huang SJ, Yen LM, Eng DM, Hsieh YD, Ger LP: A high IL-4 production diplotype is associated with an increased risk but better prognosis of oral and pharyngeal carcinomas. Arch Oral Biol. 2014, 59 (1): 35-46. 10.1016/j.archoralbio.2013.09.010.CrossRefPubMed
33.
Bozdogan ST, Erol B, Dursun A, Bozdogan G, Donmez I, Mungan NA, Seydaoglu G: The IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer: a case–control study.World J Urol 2014, [Epub ahead of print].,
34.
Zhang H, Xu Y, Zhang Z, Liu R, Ma B: Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis. BMC Immunol. 2012, 13: 14-10.1186/1471-2172-13-14.CrossRefPubMedCentralPubMed
35.
Zhang H, Qi C, Li L, Luo F, Xu Y: Clinical significance of NUCB2 mRNA expression in prostate cancer. J Exp Clin Cancer Res. 2013, 32 (1): 56-10.1186/1756-9966-32-56.CrossRefPubMedCentralPubMed
36.
Abaza MS, Bahman AM, Al-Attiyah RJ, Kollamparambil AM: Synergistic induction of apoptosis and chemosensitization of human colorectal cancer cells by histone deacetylase inhibitor, scriptaid, and proteasome inhibitors: potential mechanisms of action. Tumour Biol. 2012, 33 (6): 1951-1972. 10.1007/s13277-012-0456-6.CrossRefPubMed
37.
Sanchez-Correa B, Bergua JM, Campos C, Gayoso I, Arcos MJ, Banas H, Morgado S, Casado JG, Solana R, Tarazona R: Cytokine profiles in acute myeloid leukemia patients at diagnosis: survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine. 2013, 61 (3): 885-891. 10.1016/j.cyto.2012.12.023.CrossRefPubMed
38.
Porter GA, Abdalla J, Lu M, Smith S, Montgomery D, Grimm E, Ross MI, Mansfield PF, Gershenwald JE, Lee JE: Significance of plasma cytokine levels in melanoma patients with histologically negative sentinel lymph nodes. Ann Surg Oncol. 2001, 8 (2): 116-122. 10.1007/s10434-001-0116-3.CrossRefPubMed
39.
Lathers DM, Young MR: Increased aberrance of cytokine expression in plasma of patients with more advanced squamous cell carcinoma of the head and neck. Cytokine. 2004, 25 (5): 220-228. 10.1016/j.cyto.2003.11.005.CrossRefPubMed
40.
Shurin MR, Lu L, Kalinski P, Stewart-Akers AM, Lotze MT: Th1/Th2 balance in cancer, transplantation and pregnancy. Springer Semin Immunopathol. 1999, 21 (3): 339-359. 10.1007/BF00812261.CrossRefPubMed
41.
Mellgren K, Hedegaard CJ, Schmiegelow K, Muller K: Plasma cytokine profiles at diagnosis in pediatric patients with non-hodgkin lymphoma. J Pediatr Hematol Oncol. 2012, 34 (4): 271-275. 10.1097/MPH.0b013e3182431e02.CrossRefPubMed
42.
Pan XF, Wen Y, Loh M, Wen YY, Yang SJ, Zhao ZM, Tian Z, Huang H, Lan H, Chen F, Soong R, Yang CX: Interleukin-4 and −8 gene polymorphisms and risk of gastric cancer in a population in Southwestern China. Asian Pac J Cancer Prev. 2014, 15 (7): 2951-2957. 10.7314/APJCP.2014.15.7.2951.CrossRefPubMed
43.
Jin T, Li X, Zhang J, Wang H, Geng T, Li G, Gao G, Chen C: Genetic association between selected cytokine genes and glioblastoma in the Han Chinese population. BMC Cancer. 2013, 13: 236-10.1186/1471-2407-13-236.CrossRefPubMedCentralPubMed
44.
Monroy CM, Cortes AC, Lopez MS, D’Amelio AM, Etzel CJ, Younes A, Strom SS, El-Zein RA: Hodgkin disease risk: role of genetic polymorphisms and gene-gene interactions in inflammation pathway genes. Mol Carcinog. 2011, 50 (1): 36-46. 10.1002/mc.20688.CrossRefPubMed
45.
Olson SH, Orlow I, Simon J, Tommasi D, Roy P, Bayuga S, Ludwig E, Zauber AG, Kurtz RC: Allergies, variants in IL-4 and IL-4R alpha genes, and risk of pancreatic cancer. Cancer Detect Prev. 2007, 31 (5): 345-351. 10.1016/j.cdp.2007.10.002.CrossRefPubMed
46.
Zhenzhen L, Xianghua L, Qingwei W, Zhan G, Ning S: Three common polymorphisms in the IL-4 gene and cancer risk: a meta-analysis involving 5,392 cases and 6,930 controls. Tumour Biol. 2013, 34 (4): 2215-2224. 10.1007/s13277-013-0761-8.CrossRefPubMed
Metadata
Title
Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk
Authors
Yin Duan
Chi Pan
Jinan Shi
Hailong Chen
Suzhan Zhang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2014
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-014-0131-7

Other articles of this Issue 1/2014

Cancer Cell International 1/2014 Go to the issue

Primary research

Electromagnetic field investigation on different cancer cell lines

Primary research

The effects of phenoxodiol on the cell cycle of prostate cancer cell lines

Primary research

Correlation between HER-2/neu(erbB-2) expression level and therapeutic effect of combination treatment with HERCEPTIN and chemotherapeutic agents in gastric cancer cell lines

Primary research

Association between genetic polymorphisms in AURKA (rs2273535 and rs1047972) and breast cancer risk: a meta-analysis involving 37,221 subjects

Primary research

Abnormal expression of CDK11p58 in prostate cancer

Primary research

Mitochondrial structure alteration in human prostate cancer cells upon initial interaction with a chemopreventive agent phenethyl isothiocyanate

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

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