| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Environmental Health (Occupational Health Program) [R. F., M-T. W., D. M., K. T. K., D. C. C.] and Cancer Cell Biology [K. T. K.], Harvard School of Public Health, Boston, Massachusetts 02115; Thoracic Surgery Unit, Department of Surgery [J. C. W.], and Pulmonary and Critical Care Unit, Department of Medicine [D. C. C.], Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114; University of California at San Francisco, Department of Epidemiology and Biostatistics, San Francisco, California 94143 [J. K. W.]
The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01–2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma.
This article has been cited by other articles:
|
|
 |
|
  P. Sun, Y. Qiu, Z. Zhang, J. Wan, T. Wang, X. Jin, Q. Lan, N. Rothman, and Z.-l. Xia Association of Genetic Polymorphisms, mRNA Expression of p53 and p21 with Chronic Benzene Poisoning in a Chinese Occupational Population Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1821 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Mechanic, E. D. Bowman, J. A. Welsh, M. A. Khan, N. Hagiwara, L. Enewold, P. G. Shields, L. Burdette, S. Chanock, and C. C. Harris Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 214 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kohno, T. Sakiyama, H. Kunitoh, K. Goto, Y. Nishiwaki, D. Saito, H. Hirose, T. Eguchi, N. Yanagitani, R. Saito, et al. Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk Carcinogenesis, December 1, 2006; 27(12): 2448 - 2454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Shin, S. J. Lee, J. E. Choi, S. I. Cha, C. H. Kim, W. K. Lee, S. Kam, Y. M. Kang, T. H. Jung, and J. Y. Park Glu346Lys Polymorphism in the Methyl-CpG Binding Domain 4 Gene and the Risk of Primary Lung Cancer Jpn. J. Clin. Oncol., August 1, 2006; 36(8): 483 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Jain, V. Singh, S. Hedau, S. Kumar, M. K. Daga, R. Dewan, N. S. Murthy, S. A. Husain, and B. C. Das Infection of Human Papillomavirus Type 18 and p53 Codon 72 Polymorphism in Lung Cancer Patients From India Chest, December 1, 2005; 128(6): 3999 - 4007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sotamaa, S. Liyanarachchi, J.-P. Mecklin, H. Jarvinen, L. A. Aaltonen, P. Peltomaki, and A. de la Chapelle p53 Codon 72 and MDM2 SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome Clin. Cancer Res., October 1, 2005; 11(19): 6840 - 6844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tommiska, H. Eerola, M. Heinonen, L. Salonen, M. Kaare, J. Tallila, A. Ristimaki, K. von Smitten, K. Aittomaki, P. Heikkila, et al. Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival Clin. Cancer Res., July 15, 2005; 11(14): 5098 - 5103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hu, M. P. McDermott, and S. A. Ahrendt The p53 Codon 72 Proline Allele Is Associated with p53 Gene Mutations in Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2005; 11(7): 2502 - 2509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Mechanic, A. J. Marrogi, J. A. Welsh, E. D. Bowman, M. A. Khan, L. Enewold, Y.-L. Zheng, S. Chanock, P. G. Shields, and C. C. Harris Polymorphisms in XPD and TP53 and mutation in human lung cancer Carcinogenesis, March 1, 2005; 26(3): 597 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Scheckenbach, O. Lieven, K. Gotte, U. Bockmuhl, R. Zotz, H. Bier, and V. Balz p53 Codon 72 Polymorphic Variants, Loss of Allele-Specific Transcription, and Human Papilloma Virus 16 and/or 18 E6 Messenger RNA Expression in Squamous Cell Carcinomas of the Head and Neck Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1805 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. Xi, K.-Y. Ding, X.-L. Su, D.-F. Chen, W.-C. You, Y. Shen, and Y. Ke p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions Carcinogenesis, November 1, 2004; 25(11): 2201 - 2206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Omori, S. Yoshida, S. H. Kennedy, K. Negoro, S. Hamana, D. H. Barlow, and T. Maruo Polymorphism at Codon 72 of the p53 Gene Is Not associated With Endometriosis in a Japanese Population Reproductive Sciences, May 1, 2004; 11(4): 232 - 236. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Zhu, M. R. Spitz, C. I. Amos, J. Lin, M. B. Schabath, and X. Wu An Evolutionary Perspective on Single-Nucleotide Polymorphism Screening in Molecular Cancer Epidemiology Cancer Res., March 15, 2004; 64(6): 2251 - 2257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-W. Zhang, N. J. Laurence, A. Hollowood, P. Newcomb, M. Moorghen, J. Gupta, R. Feakins, M. J. G. Farthing, D. Alderson, and J. Holly Prognostic Value of TP53 Codon 72 Polymorphism in Advanced Gastric Adenocarcinoma Clin. Cancer Res., January 1, 2004; 10(1): 131 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Matakidou, T. Eisen, and R.S. Houlston TP53 polymorphisms and lung cancer risk: a systematic review and meta-analysis Mutagenesis, July 1, 2003; 18(4): 377 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-W. Zhang, P. Newcomb, A. Hollowood, R. Feakins, M. Moorghen, A. Storey, M. J. G. Farthing, D. Alderson, and J. Holly Age-associated Increase of Codon 72 Arginine p53 Frequency in Gastric Cardia and Non-Cardia Adenocarcinoma Clin. Cancer Res., June 1, 2003; 9(6): 2151 - 2156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A-M Martin, P A Kanetsky, B Amirimani, T A Colligon, G Athanasiadis, H A Shih, M R Gerrero, K Calzone, T R Rebbeck, and B L Weber Germline TP53 mutations in breast cancer families with multiple primary cancers: is TP53 a modifier of BRCA1? J. Med. Genet., April 1, 2003; 40(4): e34 - 34. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wu, H. Zhao, C. I. Amos, S. Shete, N. Makan, W. K. Hong, F. F. Kadlubar, and M. R. Spitz p53 Genotypes and Haplotypes Associated With Lung Cancer Susceptibility and Ethnicity J Natl Cancer Inst, May 1, 2002; 94(9): 681 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Miller, G. Liu, I. De Vivo, T. J. Lynch, J. C. Wain, L. Su, and D. C. Christiani Combinations of the Variant Genotypes of GSTP1, GSTM1, and p53 Are Associated with an Increased Lung Cancer Risk Cancer Res., May 1, 2002; 62(10): 2819 - 2823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Furihata, T. Takeuchi, M. Matsumoto, A. Kurabayashi, Y. Ohtsuki, N. Terao, M. Kuwahara, and T. Shuin p53 Mutation Arising in Arg72 Allele in the Tumorigenesis and Development of Carcinoma of the Urinary Tract Clin. Cancer Res., May 1, 2002; 8(5): 1192 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. I. Wang, D. P. Miller, Y. Sai, G. Liu, L. Su, J. C. Wain, T. J. Lynch, and D. C. Christiani Manganese Superoxide Dismutase Alanine-to-Valine Polymorphism at Codon 16 and Lung Cancer Risk J Natl Cancer Inst, December 5, 2001; 93(23): 1818 - 1821. [Full Text] [PDF]
|
|
|
|
|
|
G. Liu, D. P. Miller, W. Zhou, S. W. Thurston, R. Fan, L.-L. Xu, T. J. Lynch, J. C. Wain, L. Su, and D. C. Christiani Differential Association of the Codon 72 p53 and GSTM1 Polymorphisms on Histological Subtype of Non-Small Cell Lung Carcinoma Cancer Res., December 1, 2001; 61(24): 8718 - 8722. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
