Abstract
Purpose
This study aims to explore the associations of polymorphisms in tachykinin, precursor 1 (TAC1), tachykinin receptor 1 (TACR1), and tachykinin receptor 2 (TACR2) genes and their interactions with the risk of colorectal cancer (CRC) among Chinese population.
Methods
A population-based case-control study which included 394 cases and 393 cancer-free controls was carried out. A total of 19 tagSNPs in the three genes were chosen based on HapMap and NCBI datasets and genotyped by SNPshot assay. Multiple logistic regression models were applied to evaluate the associations of SNPs with CRC after adjustment for potential covariates. Furthermore, generalized multifactor dimensionality reduction (GMDR) method was used to test the interactive effect among three genes on CRC.
Results
Compared with those carrying rs3755457 CC/CT or rs12477554 TT/CT genotype, individuals carrying homozygous variants had higher risk of colorectal cancer (adjusted OR = 1.80, 95 % CI = 1.03–3.13, P = 0.039 for rs3755457; adjusted OR = 1.73, 95 % CI = 1.07–2.79, P = 0.024 for rs12477554). As for rs10198644, GG genotype was associated with a 1.72-fold (95 % CI = 0.37–0.88) decreased risk when compared with the common CC genotype. Moreover, the GMDR analysis indicated that the best interactive model included five polymorphisms: rs2072100 (TAC1), rs10198644 (TACR1), rs2193409 (TACR1), rs3771810 (TACR1), and rs4644560 (TACR2).
Conclusions
Our study suggests that tachykinins pathway genes may participate in the development of CRC and the potential interactions among the three genes on CRC may exist, which has to be confirmed in future larger studies.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90
Wu M, Zhang SW, Han RQ, Zhou JY, Zou XN, Chen WQ (2010) Analysis on the mortality of colorectal and anal cancer in China during 2004–2005. Zhonghua Yu Fang Yi Xue Za Zhi 44(5):403–407
Singh D, Joshi DD, Hameed M, Qian J, Gascon P, Maloof PB, Mosenthal A, Rameshwar P (2000) Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis. Proc Natl Acad Sci USA 97(1):388–393
David S, Kan T, Cheng Y, Agarwal R, Jin Z, Mori Y (2009) Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer. Biochem Biophys Res Commun 378(3):605–609
Jin Z, Olaru A, Yang J, Sato F, Cheng Y, Kan T, Mori Y, Mantzur C, Paun B, Hamilton JP, Ito T, Wang S, David S, Agarwal R, Beer DG, Abraham JM, Meltzer SJ (2007) Hypermethylation of tachykinin-1 is a potential biomarker in human esophageal cancer. Clin Cancer Res 13(21):6293–6300
Friess H, Zhu Z, Liard V, Shi X, Shrikhande SV, Wang L, Lieb K, Korc M, Palma C, Zimmermann A, Reubi JC, Buchler MW (2003) Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer. Lab Invest 83(5):731–742
Pennefather JN, Lecci A, Candenas ML, Patak E, Pinto FM, Maggi CA (2004) Tachykinins and tachykinin receptors: a growing family. Life Sci 74(12):1445–1463
Patacchini R, Lecci A, Holzer P, Maggi CA (2004) Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature. Trends Pharmacol Sci 25(1):1–3
Jaafari N, Hua G, Adelaide J, Jule Y, Imbert J (2008) Expression of the tachykinin receptor mRNAs in healthy human colon. Eur J Pharmacol 599(1–3):121–125
Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V (2002) The tachykinin peptide family. Pharmacol Rev 54(2):285–322
Watanabe T, Kubota Y, Muto T (1997) Substance P containing nerve fibers in rectal mucosa of ulcerative colitis. Dis Colon Rectum 40(6):718–725
Vento P, Kiviluoto T, Keranen U, Jarvinen HJ, Kivilaakso E, Soinila S (2001) Quantitative comparison of growth-associated protein-43 and substance P in ulcerative colitis. J Histochem Cytochem 49(6):749–758
Rosso M, Robles-Frias MJ, Covenas R, Salinas-Martin MV, Munoz M (2008) The NK-1 receptor is expressed in human primary gastric and colon adenocarcinomas and is involved in the antitumor action of L-733,060 and the mitogenic action of substance P on human gastrointestinal cancer cell lines. Tumour Biol 29(4):245–254
Ogasawara M, Murata J, Ayukawa K, Saiki I (1997) Differential effect of intestinal neuropeptides on invasion and migration of colon carcinoma cells in vitro. Cancer Lett 119(1):125–130
Fan TP, Hu DE, Guard S, Gresham GA, Watling KJ (1993) Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition by NK1 or interleukin-1 receptor antagonists. Br J Pharmacol 110(1):43–49
Rameshwar P, Gascon P (1996) Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma. Blood 88(1):98–106
Reeve JG, Bleehen NM (1994) [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P induces apoptosis in lung cancer cell lines in vitro. Biochem Biophys Res Commun 199(3):1313–1319
Fan C, Jin M, Chen K, Zhang Y, Zhang S, Liu B (2007) Case-only study of interactions between metabolic enzymes and smoking in colorectal cancer. BMC Cancer 7:115
Nasiri H, Forouzandeh M, Rasaee MJ, Rahbarizadeh F (2005) Modified salting-out method: high-yield, high-quality genomic DNA extraction from whole blood using laundry detergent. J Clin Lab Anal 19(6):229–232
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265
Lou XY, Chen GB, Yan L, Ma JZ, Zhu J, Elston RC, Li MD (2007) A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence. Am J Hum Genet 80(6):1125–1137
Hennig IM, Laissue JA, Horisberger U, Reubi JC (1995) Substance-P receptors in human primary neoplasms: tumoral and vascular localization. Int J Cancer 61(6):786–792
Akazawa T, Kwatra SG, Goldsmith LE, Richardson MD, Cox EA, Sampson JH, Kwatra MM (2009) A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas. J Neurochem 109(4):1079–1086
Munoz M, Rosso M, Aguilar FJ, Gonzalez-Moles MA, Redondo M, Esteban F (2008) NK-1 receptor antagonists induce apoptosis and counteract substance P-related mitogenesis in human laryngeal cancer cell line HEp-2. Invest New Drugs 26(2):111–118
Nowicki M, Miskowiak B (2003) Substance P—a potent risk factor in childhood lymphoblastic leukaemia. Leukemia 17(6):1096–1099
Luo W, Sharif TR, Sharif M (1996) Substance P-induced mitogenesis in human astrocytoma cells correlates with activation of the mitogen-activated protein kinase signaling pathway. Cancer Res 56(21):4983–4991
Munoz M, Rosso M, Perez A, Covenas R, Rosso R, Zamarriego C, Soult JA, Montero I (2005) Antitumoral action of the neurokinin-1-receptor antagonist L-733,060 and mitogenic action of substance P on human retinoblastoma cell lines. Invest Ophthalmol Vis Sci 46(7):2567–2570
Munoz M, Rosso M, Perez A, Covenas R, Rosso R, Zamarriego C, Piruat JI (2005) The NK1 receptor is involved in the antitumoural action of L-733,060 and in the mitogenic action of substance P on neuroblastoma and glioma cell lines. Neuropeptides 39(4):427–432
Palma C (2006) Tachykinins and their receptors in human malignancies. Curr Drug Targets 7(8):1043–1052
Reubi JC (1997) Regulatory peptide receptors as molecular targets for cancer diagnosis and therapy. Q J Nucl Med 41(2):63–70
Reubi JC, Zimmermann A, Jonas S, Waser B, Neuhaus P, Laderach U, Wiedenmann B (1999) Regulatory peptide receptors in human hepatocellular carcinomas. Gut 45(5):766–774
Cunningham S, Patterson CC, McDonnell G, Hawkins S, Vandenbroeck K (2005) Haplotype analysis of the preprotachykinin-1 (TAC1) gene in multiple sclerosis. Genes Immun 6(3):265–270
Giegling I, Rujescu D, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, De Ronchi D, Moller HJ, Serretti A (2007) Tachykinin receptor 1 variants associated with aggression in suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 144B(6):757–761
Renner SP, Ekici AB, Maihofner C, Oppelt P, Thiel FC, Schrauder M, Uenluehan N, Bani MR, Strissel PL, Strick R, Beckmann MW, Fasching PA (2009) Neurokinin 1 receptor gene polymorphism might be correlated with recurrence rates in endometriosis. Gynecol Endocrinol 25(11):726–733
Friedrich P, Feulner TM, Laws SM, Eckart K, Perneczky R, Kurz A, Forstl H, Riemenschneider M (2011) No association of tachykinin receptor 2 (TACR2) polymorphisms with Alzheimer's disease. Neurobiol Aging 32(3):544–545
Acknowledgements
The study was funded in part by grants from the New Teacher Foundation of the Ministry of Education (20090101120103), Natural Science Foundation of Zhejiang Province (Y2090154 and Y2110499), Department of Education of Zhejiang Province (Z200804565), and Zhejiang Foundation of Young Teachers' innovation (2009QNA7018). We are grateful to all participants for agreeing to take part in our study. We also thank the staff of Cancer Institute of Jiashan County for their continuous support and assistance to collect the epidemiological data and blood specimen.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOC 177 kb)
Rights and permissions
About this article
Cite this article
Yu, Y., Pan, Y., Jin, M. et al. Association of genetic variants in tachykinins pathway genes with colorectal cancer risk. Int J Colorectal Dis 27, 1429–1436 (2012). https://doi.org/10.1007/s00384-012-1478-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00384-012-1478-7