Analysis of TP53 Polymorphisms in North Indian Sporadic Esophageal Cancer Patients

  • Kaur, Sukhpreet (Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University) ;
  • Sambyal, Vasudha (Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University) ;
  • Guleria, Kamlesh (Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University) ;
  • Manjari, Mridu (Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Sudan, Meena (Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Uppal, Manjit Singh (Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Singh, Neeti Rajan (Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Singh, Gursimran (Dr. D.Y. Patel Medical College and Hospital) ;
  • Singh, Harpreet (Liver & Digestive Diseases Centre)
  • Published : 2014.10.23


Background: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. Materials and Methods: Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadic EC patients and 136 controls using polymerase chain reaction and PCR-RFLP. Results: The frequencies of genotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27% among patients and controls respectively. We observed significantly increased frequency of RP genotype in cases as compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 and A2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patients and controls. There was no significant difference among genotype and allele distribution between patients and controls. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56 vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotype and allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, all the cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination shows significant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). Conclusions: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility.


Esophageal cancer;TP53;polymorphism


  1. Ali I, Wani WA, Saleem K (2011). Cancer scenario in India with future perspectives. Cancer Therapy, 8, 56-70.
  2. Adeli K, Ogbonna G (1990). Rapid purification of human DNA from whole blood for potential application in clinical chemistry laboratories. Clin Chem, 36, 261-4.
  3. Akkiprik M, Sonmez O, Gulluoglu BM, et al (2009). Analysis of p53 gene polymorphisms and protein over-expression in patients with breast cancer. Pathol Oncol Res, 15, 359-68.
  4. Alawadi S, Ghabreau L, Alsaleh M, et al (2011). P53 gene polymorphisms and breast cancer risk in Arab women. Med Oncol, 28, 709-15.
  5. Almeida LO, Custodio AC, Pinto GR, et al (2009). Polymorphisms and DNA methylation of gene TP53 associated with extraaxial brain tumors. Genet Mol Res, 8, 8-18.
  6. Al-Qasem A, Toulimat M, Tulbah A, et al (2012). The p53 codon 72 polymorphism is associated with the risk and early onset of breast cancer among Saudi women. Oncol Lett, 3, 875-8.
  7. Bergamaschi D, Gasco M, Hiller L, et al (2003). p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell, 3, 387-402.
  8. Biros E, Kalina I, Kohut A, Stubna J, Salagovic J (2001). Germ line polymorphisms of the tumor suppressor gene p53 and lung cancer. Lung Cancer, 31, 157-62.
  9. Cescon DW, Bradbury PA, Asomaning K, et al (2009). p53 Arg72Pro and MDM2 T309G polymorphisms, histology and esophageal cancer prognosis. Clin Cancer Res, 15, 3103-9.
  10. Bojesen SE, Nordestgaard BG (2008). The common germline Arg72Pro polymorphism of p53 and increased longevity in humans. Cell Cycle, 7, 158-63.
  11. Cai L, Mu LN, Lu H, et al (2006). Dietary selenium intake and genetic polymorphisms of the GSTP1 and p53 genes on the risk of esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 294-300.
  12. Castellsaque X, Quintana MJ, Martinez MC, et al (2004). The role of type of tobacco and type of alcoholic beverage in oral carcinogenesis. Int J Cancer, 108, 741-9.
  13. Chansaenroj J, Theamboonlers A, Junyangdikul P, et al (2013). Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566) genes in Thai cervical cancer patients with HPV 16 infection. Asian Pac J Cancer Prev, 14, 341-6.
  14. Chen K, Hu Z, Wang LE, et al (2007). Polymorphic TP53BP1 and TP53 gene interactions associated with risk of squamous cell carcinoma of the head and neck. Clin Cancer Res, 13, 4300-5.
  15. Cherdyntseva NV, Gervas PA, Litvyakov NV, et al (2010). Agerelated function of tumor suppressor gene TP53: contribution to cancer risk and progression. Exp Oncol, 32, 205-8.
  16. Costa S, Pinto D, Pereira D, et al (2008). Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer. BMC Cancer, 8, 32.
  17. Daugherty CL, Curtis H, Realini T, Charlton JF, Zareparsi S (2009). Primary open angle glaucoma in a Caucasian population is associated with the p53 codon 72 polymorphism. Mol Vis, 15, 1939-44.
  18. Gallus S, Vecchia CL, Levi F, et al (2001). Leaness and squamous cell oesophageal cancer. Ann Oncol, 12, 975-9.
  19. Dumont P, Leu JI, Della Pietra AC 3rd, George DL, Murphy M (2003). The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet, 33, 357-65.
  20. Felley-Bosco E, Weston A, Cawley HM, Bennett WP, Harris CC (1993). Functional studies of a germ-line polymorphism at codon 47 within the p53 gene. Am J Hum Genet, 53, 752-59.
  21. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.
  22. Franceschi S, Talamini R, Barra S, et al (1990). Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx and esophagus in northern Italy. Cancer Res, 50, 6502-7.
  23. Gemingnani F, Moreno V, Landi S, et al. (2004) A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene, 23, 1954-6.
  24. Gervas P, Litvyakov N, Stacheeva M, et al (2009). Influence of apoptosis and repair gene polymorphism on neoadjuvant chemotherapy response of malignant tumors. Siberian J Oncol, 34, 41-7.
  25. Guimaraes DP, Lu SH, Snijders P, et al (2001). Absence of association between HPV DNA, TP53 codon 72 polymorphism, and risk of oesophageal cancer in a high-risk area of China. Cancer Lett, 162, 231-5.
  26. Hainaut P, Hollstein M (2000). P53 and human cancer: the first ten thousand mutations. Adv Cancer Res, 77, 81-137.
  27. Hamajima N, Matsuo K, Suzuki T, et al (2002). No associations of p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese. Cancer Lett, 181, 81-5.
  28. Haupt S, Haupt Y (2006). Importance of p53 for cancer onset and therapy. Anticancer Drugs, 17, 725-32.
  29. Hamroun D, Kato S, Ishioka C, et al (2006). The UMD TP53 database and website: update and revisions. Hum Mutat, 27, 14-20.
  30. Harris CC, Hollstein M (1993). Clinical implications of the p53 tumor-suppressor gene. N Engl J Med, 329, 1318-27.
  31. Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J (2003). Ageing and genome maintenance: lessons from the mouse? Science, 299, 1355-9.
  32. He B, Duan G, Zhang W, et al (2005). Study on p53 codon 72 polymorphism and human papillomavirus-associated esophageal cancer in Anyang area, Henan Province. Henan J Prev Med, 16, 67-9.
  33. Hong Y, Miao X, Zhang X, et al (2005). The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma. Cancer Res, 65, 9582-7.
  34. Hosking L, Lumsden S, Lewis K, et al (2004). Detection of genotyping errors by Hardy-Weinberg equilibrium testing. Eur J Hum Genet, 12, 395-9.
  35. Hrstka R, Beranek M, Klocova K, Nenutil R, Vojtesek B (2009). Intronic polymorphisms in TP53 indicate lymph node metastasis in breast cancer. Oncol Rep, 22, 1205-11.
  36. Hu N, Li WJ, Su H, et al (2003). Common genetic variants of TP53 and BRCA2 in esophageal cancer patients and healthy individuals from low and high risk areas of northern China. Cancer Detect Prev, 27, 132-8.
  37. Hunt CR, Ramnarain D, Horikoshi N, et al (2013). Histone modifications and DNA double-strand break repair after exposure to ionizing radiations. Radiat Res, 179, 383-92.
  38. IARC (2014) IARC TP53 Database, Gene Variations. Available at Accessed June 25, 2014.
  39. Kawaguchi H, Ohno S, Araki K, et al (2000). p53 polymorphism in human papillomavirus-associated esophageal cancer. Cancer Res, 60, 2753-5.
  40. Jaiswal PK, Goel A, Mittal RD (2011). Association of p53 codon 248 (exon7) with urinary bladder cancer risk in the North Indian population. Biosci Trends, 5, 205-10.
  41. Jiang DK, Yao L, Wang WZ, et al (2011). TP53 Arg72Pro polymorphism is associated with esophageal cancer risk: A meta-analysis. World J Gastroenterol, 17, 1227-3.
  42. Johnstone RW, Ruefli AA, Lowe SW (2002). Apoptosis: a link between cancer genetics and chemotherapy. Cell, 108, 153-64.
  43. Kazemi M, Salehi Z, Chakosari RJ (2009). TP53 codon 72 polymorphism and breast cancer in northern Iran. Oncol Res, 18, 25-30.
  44. Kirkwood TB, Austad SN (2000). Why do we age? Nature, 408, 233-8.
  45. Launoy G, Milan CH, Faivre J, et al (1997). Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption, mean intake and current and former consumption. Br J Cancer, 75, 1389-96.
  46. Lee CH, Lee JM, Wu DC, et al (2005). Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan. Int J Cancer, 113, 475-82.
  47. Lee JM, Lee YC, Yang SY, et al (2000). Genetic polymorphisms of P53 and GSTP1, but not NAT2, are associated with susceptibility to squamous-cell carcinoma of the esophagus. Int J Cancer, 89, 458-64.<458::AID-IJC10>3.0.CO;2-R
  48. Lehman TA, Haffty BG, Carbone CJ, et al (2000). Elevated frequency and functional activity of a specific germline p53 intron mutation in familial breast cancer. Cancer Res, 60, 1062-9.
  49. Levine AJ (1997). p53, the cellular gatekeeper for growth and division. Cell, 88, 323-31.
  50. Liu G, Cescon DW, Zhai R, et al (2010). p53 Arg72Pro, MDM2 T309G and CCND1 G870A polymorphisms are not associated with susceptibly to esophageal adenocarcinoma. Dis Esophagus, 23, 36-9.
  51. Levine AJ, Oren M (2009). The first 30 years of p53: growing ever more complex. Nat Rev Cancer, 9, 749-58.
  52. Li T, Lu ZM, Guo M, et al (2002). p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinoma in China. Cancer, 95, 2571-6.
  53. Li X, Dumont P, Della Pietra A, et al (2005). The codon 47 polymorphism in p53 is functionally significant. J Biol Chem, 280, 24245-51.
  54. Lozano G, Zambetti GP (2005). What have animal models taught us about the p53 pathway? J Pathol, 205, 206-20.
  55. Lu XM, Zhang YM, Lin RY, et al (2004). p53 polymorphism in human papillomavirus-associated Kazakh's esophageal cancer in Xinjiang, China. World J Gastroenterol, 10, 2775-8.
  56. Ma J, Zhang J, Ning T, Chen Z, Xu C (2012). Association of genetic polymorphisms in MDM2, PTEN and P53 with the risk of esophageal squamous cell carcinoma. J Hum Genet, 57, 261-4.
  57. Malik MA, Sharma K, Goel S, Zargar SA, Mittal B (2011). Association of TP53 intron 3, 16bp duplication polymorphism with esophageal and gastric cancer susceptibility in Kashmir Valley. Oncol Res, 19, 165-9.
  58. Malkinson AM, You M (1994). The intronic structure of cancer-related genes regulates susceptibility to cancer. Mol Carcinog, 10, 61-5.
  59. Mammano E, Belluco C, Bonafe M, et al (2009). Association of p53 polymorphisms and colorectal cancer: modulation of risk and progression. Eur J Surg Oncol, 35, 415-9.
  60. Mavridou D, Gornall R, Campbell IG, Eccles DM (1998). TP53 intron 6 polymorphism and the risk of ovarian and breast cancer. Br J Cancer, 77, 676-7.
  61. Mao WM, Zheng WH, Ling ZQ (2011). Epidemiology risk factors for esophageal cancer development. Asian Pac J Cancer Prev, 12, 2461-6.
  62. Mattick JS (1994). Introns: evolution and function. Curr Opin Genet Dev, 4, 823-31.
  63. Mattick JS (2004). RNA regulation: a new genetics? Nat Rev Genet, 5, 316-23.
  64. Mazars GR, Jeanteur P, Lynch HT, Lenoir G, Theillet C (1992). Nucleotide sequence polymorphism in a hotspot mutation region of the p53 gene. Oncogene, 7, 781-2.
  65. Meyer A, Alexandre PC, Chrisman Jde R, et al (2011). Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates. Int J Hyg Environ Health, 214, 151-5.
  66. Mitchell AA, Cutler DJ, Chakravarti A (2003). Undetected genotyping errors cause apparent overtransmission of common alleles in the transmission/disequilibrium test. Am J Hum Genet, 72, 598-610.
  67. Mitra S, Chatterjee S, Panda CK, et al (2003). Haplotype structure of TP53 locus in Indian population and possible association with head and neck cancer. Ann Hum Genet, 67, 26-34.
  68. Mitra S, Misra C, Singh RK, Panda CK, Roychoudhury S (2005). Association of specific genotype and haplotype of p53 gene with cervical cancer in India. J Clin Pathol, 58, 26-31.
  69. Mittal RD, George GP, Mishra J, Mittal T, Kapoor R (2011). Role of functional polymorphisms of P53 and P73 genes with the risk of prostate cancer in a case-control study from Northern India. Arch Med Res, 42, 122-7.
  70. Nelson HH, Wilkojmen M, Marsit CJ, Kelsey KT (2005). TP53 mutation, allelism and survival in non-small cell lung cancer. Carcinogenesis, 26, 1770-3.
  71. Mohiuddin MK, Chava S, Upendrum P, et al (2013). Role of Human papilloma virus infection and altered methylation of specific genes in esophageal cancer. Asian Pac J Cancer Prev, 14, 4187-93.
  72. Murphy ME (2006). Polymorphic variants in the p53 pathway. Cell Death Differ, 13, 916-20.
  73. Muwonge R, Ramadas K, Sankila R, et al (2008). Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: a nested case-control design using incident cancer cases. Oral Oncol, 44, 446-54.
  74. Owen RG, Davis SA, Randerson J, et al (1997). p53 gene mutations in multiple myeloma. Mol Pathol, 50, 18-20.
  75. Pantelis A, Pantelis D, Ruemmele P, et al (2007). p53 codon 72 polymophism, loss of heterozygosity and high-risk human papillomavirus infection in a low-incidence German esophageal squamous cell carcinoma patient cohort. Oncol Rep, 17, 1243-8.
  76. Peller S, Kopilova Y, Slutzki S, et al (1995). A novel polymorphism in intron 6 of the human p53 gene: a possible association with cancer predisposition and susceptibility. DNA Cell Biol, 14, 983-90.
  77. Perfumo C, Bonelli L, Menichini P, et al (2006). Increased risk of colorectal adenomas in Italian subjects carrying the p53 PIN3 A2-Pro72 haplotype. Digestion, 74, 228-35.
  78. Petitjean A, Mathe E, Kato S, et al (2007). Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat, 28, 622-9.
  79. Ren YW, Yin ZH, Wan Y, et al (2013). P53 Arg72Pro and MDM2 SNP309 polymorphisms cooperate to increase lung adenocarcinoma risk in Chinese female non-smokers: a case control study. Asian Pac J Cancer Prev, 14, 5415-20.
  80. Piao JM, Kim HN, Song HR, et al (2011). p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case-control study. Dis Esophagus, 24, 596-600.
  81. Pilger DA, Lopez PL, Segal F, Leistner-Segal S (2007). Analysis of R213R and 13494 g>a polymorphisms of the p53 in individuals with esophagitis, intestinal metaplasia of the cardia and Barrett's Esophagus compared with a control group. Genomic Med, 1, 57-63.
  82. Pinto GR, Yoshioka FK, Silva RL, et al (2008). Prognostic value of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms and susceptibility to gliomas in individuals from Southeast Brazil. Genet Mol Res, 7, 207-16.
  83. Renouf DJ, Zhai R, Sun B, et al (2013). Association of MDM2 T309G and p53 Arg72Pro polymorphisms and gastroesophageal reflux disease with survival in esophageal adenocarcinoma. J Gastroenterol Hepatol, 28, 1482-8.
  84. Rogler A, Rogenhofer M, Borchardt A, et al (2011). P53 codon 72 (Arg72Pro) polymorphism and prostate cancer risk: association between disease onset and proline genotype. Pathobiology, 78, 193-200.
  85. Ryan AM, Rowley SP, Fitegerald AP, Ravi N, Reynolds JV (2006). Adenocarcinoma of the oesophagus and gastric cardia: male preponderance in association with obesity. Eur J Cancer, 42, 1151-8.
  86. Sakamuro D, Sabbatini P, White E, Prendergast GC (1997). The polyproline region of p53 is required to activate apoptosis but not growth arrest. Oncogene, 15, 887-98.
  87. Sameer AS, Shah ZA, Syeed N, et al (2010). TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population. Genet Mol Res, 9, 651-60.
  88. Singamsetty GK, Malempati S, Bhogadhi S, et al (2014). TP53 alterations and colorectal cancer predisposition in south Indian population: a case-control study. Tumor Biol, 35, 2303-11.
  89. Santos LE, Guilhen AC, de Andrade RA, Sumi LG, Ward LS (2011). The role of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms in the susceptibility to bladder cancer. Urol Oncol, 29, 291-4.
  90. Shao Y, Tan W, Zhang S (2008). P53 gene codon 72 polymorphism and risk of esophageal squamous cell carcinoma: a case/control study in a Chinese Population. Dis Esophagus, 21, 139-43.
  91. Siddique MM, Balram C, Fiszer-MalisZewska L, et al (2005). Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development. Cancer Epidemiol Biomarkers Prev, 14, 2245-52.
  92. Singh V, Rastogi N, Mathur N, Singh K, Singh MP (2008). Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women. Ann Epidemiol, 18, 48-57.
  93. Sjalander A, Birgander R, Hallmans G, et al (1996). p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis, 17, 1313-16.
  94. Smith M, Zhou M, Whitlock G, et al (2008). Esophageal cancer and body mass index: results from prospective study of 220,000 men in China and meta-analysis of published studies. Int J Cancer, 122, 1604-10.
  95. Stacey SN, Sulem P, Jonasdottir A, et al (2011). A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. Nat Genet, 43, 1098-103.
  96. Steyerberg EW, Neville B, Weeks JC, Earle CC (2007). Referral patterns, treatment choices, and outcomes in locoregional esophageal cancer: a population-based analysis of elderly patients. J Clin Oncol, 25, 2389-96.
  97. Thomas M, Kalita A, Labrecque S, et al (1999). Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol, 19, 1092-100.
  98. Sullivan A, Syed N, Gasco M, et al (2004). Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo. Oncogene, 23, 3328-37.
  99. Suzuki K, Matsubara H (2011). Recent advances in p53 research and cancer treatment. J Biomed Biotechnol, 2011, 978312.
  100. Takiar R, Nadayil D, Nandakumar A (2010). Projections of number of cancer cases in India (2010-2020) by cancer groups. Asian Pac J Cancer Prev, 11, 1045-9.
  101. Tommiska J, Eerola H, Heinonen M, et al (2005). Breast cancer patients with p53 Pro72 homozygous genotype have a poorer survival. Clin Cancer Res, 11, 5098-103.
  102. Tsigris C, Chatzitheoflaktou A, Xiromeritis C, Nikiteas N, Yannopoulos A (2007). Genetic association studies in digestive system malignancies. Anticancer Res, 27, 3577-88.
  103. Umar M, Upadhyay R, Khurana R, et al (2012). Role of p53 and p73 genes polymorphisms in susceptibily to esophageal cancer: a case control study in a northern Indian population. Mol Biol Rep, 39, 1153-62.
  104. Vogelstein B, Kinzler KW (1993). The multistep nature of cancer. Trends Genet, 9, 138-41.
  105. Vogelstein B, Lane D, Levine AJ (2000). Surfing the p53 network. Nature, 408, 307-10.
  106. Vos M, Adams CH, Victor TC, van Helden PD (2003). Polymorphisms and mutations found in the regions flanking exons 5 to 8 of the TP53 gene in a population at high risk for esophageal cancer in South Africa. Cancer Genet Cytogenet, 140, 23-30.
  107. Wade M, Li YC, Wahl GM (2013). MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer, 13, 83-96.
  108. Weston A, Pan CF, Ksieski HB, et al (1997). p53 haplotype determination in breast cancer. Cancer Epidemiol Biomarkers Prev, 6, 105-12.
  109. Wang W, Spitz MR, Yang H, et al (2007). Genetic variants in cell cycle control pathway confer susceptibility to lung cancer. Clin Cancer Res, 13, 5974-81.
  110. Wang-Gohrke S, Becher H, Kreienberg R, Runnebaum IB, Chang-Claude J (2002). Intron 3 16bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years. Pharmacogenetics, 12, 269-72.
  111. Wang-Gohrke S, Weikel W, Risch H, et al (1999). Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations. Br J Cancer, 81, 179-83.
  112. Whibley C, Pharoah PD, Hollstein M (2009). p53 polymorphisms: cancer implications. Nat Rev Cancer, 9, 95-107.
  113. Wu M, Zhang ZF, Kampman E, et al (2011). Does family history of cancer modify the effects of lifestyle risk factors on esophageal cancer? a population-based case-control study in China. Int J Cancer, 128, 2147-57.
  114. Xu Y, Yao L, Ouyang T, et al (2005). p53 Codon 72 polymorphism predicts the pathologic response to neoadjuvant chemotherapy in patients with breast cancer. Clin Cancer Res, 11, 7328-33.
  115. Yair D, Baruch GB, Chetrit A, et al (2000). p53 and WAFl polymorphisms in Jewish-Israeli women with epithelial ovarian cancer and its association with BRCA mutations. Br J Obs Gynae, 107, 849-54.
  116. Yang J, Liu B, Li W, et al (2013). Association of p53 and MDM2 polymorphisms with the risk of human papillomavirus (HPV)-related esophageal Squamous cell carcinoma (ESCC). Cancer Epidemiol, 37, 629-33.
  117. Yang W, Zhang Y, Tian X, Ning T, Ke Y (2008). p53 codon 72 polymorphism and the risk of esophageal squamous cell carcinoma. Mol Carcinog, 47, 100-4.
  118. Zambon P, Talamini R, Vecchia CL, et al (2000). Smoking, type of alcoholic beverage and squamous-cell oesophageal cancer in northern Italy. Int J Cancer, 86, 144-9.<144::AID-IJC23>3.0.CO;2-B
  119. Zhou X, Gu Y, Zhang SL (2012). Association between p53 codon 72 polymorphism and cervical cancer risk among Asians: a HuGE review and meta-analysis. Asian Pac J Cancer Prev, 13, 4909-14.

Cited by

  1. No Association between the CCR5Δ32 Polymorphism and Sporadic Esophageal Cancer in Punjab, North-West India vol.16, pp.10, 2015,
  2. No association of TP53 codon 72 and intron 3 16-bp duplication polymorphisms with breast cancer risk in Chinese Han women: new evidence from a population-based case–control investigation vol.23, pp.1, 2018,