Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with oral cancer

Springer Science and Business Media LLC - Tập 2 - Trang 83-89 - 2018
Sejal Shah1,2, Girish Mishra3, Kiran Kalia1,4
1Lab #103 B, BRD School of Biosciences, Sardar Patel University, Vallabh Vidhyanagar, India
2Department of Microbiology, School of Science, RK University, Rajkot, India
3Otolaryngologist and Head and Neck Surgeon, E N T Department, P. S. Medical College, Karamsad, India
4National Institute of Pharmaceuticals Education and Research (NIPER) Ahmedabad, Gandhinagar, India

Tóm tắt

Oral squamous cell carcinoma (OSCC)—a subset of head and neck cancer is the sixth most common cancer worldwide and leading disease in India. The genes involved in PI3 K/AKT (Phosphatidylinositol 3-kinase—Akt) pathway, such as PIK3CA (Phosphoinositide-3-kinase catalytic α) and PTEN (Phosphatase and tensin homologue) were found to be associated with OSCC. The present study was aimed to find the genetic association of various polymorphisms in intron 9 of the PIK3CA gene and intron 5 of PTEN gene with primary OSCC tumors. 50 OSCC patients for PIK3CA gene, 60 OSCC patients for PTEN gene and 72 healthy individuals were included in the study. PCR-direct sequencing analyzed the polymorphisms in intron 9 of PIK3CA and intron 5 of PTEN gene. We observed rs114587137 (C>T) and rs17849071 (T>G) SNPs in intron 9 of the PIK3CA gene and rs35560700 (C>T) SNP in intron 5 of the PTEN gene. T allele of rs17849071 (T>G) was associated with the high-risk allele for developing OSCC; while G allele seemed to have the protective effect against OSCC (P = 0.02). We found an inverse association of rs17849071 (T>G) with OSCC development.

Tài liệu tham khảo

India Project Team of ICGC (2013) Mutational landscape of gingivobuccal oral squamous cell carcinoma reveals new recurrently mutated genes and molecular subgroups. Nat Commun 4:2873 Anantharaman D, Chaubal PM, Kannan S, Bhisey RA, Mahimkar MB (2007) Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis 28(7):1455–1462 Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108 Jayalekshmi PA, Gangadharan P, Akiba S et al (2011) Oral cavity cancer risk in relation to tobacco chewing, bidi smoking among men in Karunagappally, Kerala, India: Karunagappally cohort study. Cancer Sci 102:460–467 Du L, Shen J, Weems A, Lu S-L (2012) Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. J Oncol 2012:1–12 Molinolo AA, Amornphimoltham P, Squarize CH, Castilho RM, Patel V, Gutkind SJ (2009) Dysregulated molecular networks in head and neck carcinogenesis. Oral Oncol 45:324–334 Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22 Kang S, Bader AG, Vogt PK (2005) Phosphatisidynositol 3 kinase mutations identified in human cancer are oncogenic. PNAS 102(3):802–807 Qiu W, Schönleben F, Li X et al (2006) PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 12:1441–1446 Ma Z et al (2013) Role of KAI1/CD82 polymorphisms in colon cancer risk in Han Chinese population. Med Oncol 30(3):668 Xing JC, Tufano RP, Murugan AK, Liu D, Wand G et al (2012) Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with follicular thyroid cancer and PIK3CA amplification. PLoS One 7(11):e49192 Liu P, Cheng H, Roberts TM et al (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8:627–644 Collins F, Brooks L, Chakravarti A (1998) A DNA polymorphism discovery resource for research on human genetic variation. Genome Res 8(12):1229–1231 Wang X, Tomso D, Liu X, Bell D (2005) Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes. Toxicol Appl Pharmacol 207(2):84–90 Liu Z, Wei S, Ma H, Zhao M, Myers JN, Weber RS, Sturgis EM, Wei Q (2011) A functional variant at the miR-184 binding site in TNFAIP2 and risk of squamous cell carcinoma of the head and neck. Carcinogenesis 32(11):1668–1674 Shah S, Shah S, Padh H, Kalia K (2015) Genetic alterations of the PIK3CA oncogene in human oral squamous cell carcinoma in an Indian population. Oral Surg Oral Med Oral Pathol Oral Radiol 120(5):628–635 Kostakis GC, Papadogeorgakis N, Koumaki V, Kamakari S, Koumaki D, Alexandridis C (2010) Absence of hotspot mutations in exons 9 and 20 of the PIK3CA gene in human oral squamous cell carcinoma in the Greek population. Oral Surg Oral Med Oral Pathol Oral Radiol 109:53–58 Tanwar R, Iyengar AR, Nagesh KS, Patil S, Subhash BV (2015) Prevalence of glutathione S-transferase M1 null polymorphism in tobacco users, oral leukoplakia and oral squamous cell carcinoma patients in South Indian population: a polymerase chain reaction study. Contemp Clin Dent 6(Suppl 1):S59–S64 Kietthubthew S, Sriplung H, Au W, Ishida T (2006) Polymorphism in DNA repair genes and oral squamous cell carcinoma in Thailand. Int J Hyg Environ Health 209(1):21–29 Tu H, Wu C, Kao S, Liu C, Liu T, Lui M (2007) Functional − 1562 C-to-T polymorphism in matrix metalloproteinase-9 (MMP-9) promoter is associated with the risk for oral squamous cell carcinoma in younger male areca users. J Oral Pathol Med 36(7):409–414 Yen C, Liu S, Chen C, Tseng H, Chuang L, Yang C et al (2008) Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan. J Oral Pathol Med 37(5):271–277 Dahia PM (2000) PTEN, a unique tumor suppressor gene. Endocr Relat Cancer 7:115–129 Yamada KM, Araki M (2001) Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci 114:2375–2382 Bu S, Asano Y, Bujor A, Highland K, Hant F, Trojanowska M (2010) Dihydrosphingosine 1-phosphate has a potent antifibrotic effect in scleroderma fibroblasts via normalization of phosphatase and tensin homolog levels. Arthritis Rheum 62:2117–2126 Hao LS, Zhang XL, An JY, Karlin J, Tian XP, Dun ZN, Xie SR, Chen S (2009) PTEN expression is down-regulated in liver tissues of rats with hepatic fibrosis induced by biliary stenosis. APMIS 117:681–691 Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, Gunn A, Nakagawa Y, Shimano H, Todorov I, Rossi JJ, Natarajan R (2009) TGF beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol 11:881–889 Xia H, Diebold D, Nho R, Perlman D, Kleidon J, Kahm J, Avdulov S, Peterson M, Nerva J, Bitterman P, Henke C (2008) Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis. J Exp Med 205:1659–1672 Kuwano K (2006) PTEN as a new agent in the fight against fibrogenesis. Am J Respir Crit Care Med 173:5–6 Teunissen BE, Smeets PJ, Willemsen PH, De Windt LJ, Van der Vusse GJ, Van Bilsen M (2007) Activation of PPAR delta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Cardiovasc Res 75:519–529 Shah S, Jajal D, Mishra G, Kalia K (2017) Genetic profile of PTEN gene in Indian oral squamous cell carcinoma primary tumors. J Oral Pathol Med 46(2):106–111