Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Jan;91(1):9–15. doi: 10.1111/j.1349-7006.2000.tb00854.x

Lack of Evidence of Association of p21WAF1/CIP1 Polymorphism with Lung Cancer Susceptibility and Prognosis in Taiwan

Chuen‐Ming Shih 1,2, Pey‐Tzy Lin 3, Hui‐Chun Wang 3, Wei‐Chi Huang 3, Yi‐Ching Wang 4,
PMCID: PMC5926229  PMID: 10744039

Abstract

An association between the Arg allele of the p21WAF1/CIP1 codon 31 polymorphism and lung cancer has been reported. However, the genotype distribution of the p21 codon 31 polymorphism, as well as the association of this polymorphism with lung cancer risk and prognosis, remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of the p21 codon 31 polymorphism in 155 lung cancer patients and 189 non‐cancer controls. The genotype frequencies in the Taiwanese non‐cancer controls were 0.51 (Ser) and 0.49 (Arg). χ2 analysis indicated significant differences in Taiwanese genotype distribution of p21 from those reported for Swedes (P=0.001), Caucasians (P=0.001), Indians (P=0.001), and African‐Americans (P=0.001). However, our data did not demonstrate an association of the Arg allele of the p21 polymorphism with lung cancer risk in Taiwan. Lung cancer patients with Ser/Arg and Arg/Arg genotypes were at a nonsignificant 1.15‐fold increased risk of lung cancer when compared to individuals with the Ser/Ser genotype (95%CI, 0.70–1.86). In addition, although p21 is a downstream target of p53, we found no significant correlation of the p21 polymorphism with the p53 polymorphism and p53 gene mutation in lung cancer patients. We further investigated the association of the p21 polymorphism with prognosis in 154 lung cancer patients. Patients with the Ser/Ser genotype tended to have a poorer prognosis than those with the Ser/Arg and Arg/Arg genotypes (P=0.097, by the log rank test). Our data suggest that the p21 codon 31 polymorphism may not play a significant role in cancer susceptibility and the prognosis of lung cancer patients in Taiwan.

Keywords: Lung cancer, p21 codon 31 polymorphism, Susceptibility, Prognosis, p53 tumor suppressor gene

Full Text

The Full Text of this article is available as a PDF (82.1 KB).

REFERENCES

  • 1. ) Kastan , M. B. , Zhan , Q. , El‐Deiry , W. S. , Carrier , F. , Jacks , T. , Walsh , W. V. , Plunkett , B. S. , Vogelstein , B. and Fornace , A. J. , Jr.A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxiatelangiectasia . Cell , 71 , 587 – 597 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) El‐Deiry , W. S. , Tokino , T. , Velculescu , V. E. , Levy , D. B. , Parsons , R. , Trent , J. M. , Lin , D. , Mercer , W. E. , Kinzler , K. W. and Vogelstein , B.WAF1, a potential mediator of p53 tumor suppression . Cell , 75 , 817 – 825 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Xiong , Y. , Hannon , G. J. , Zhang , H. , Casso , D. , Kobayashi , R. and Beach , D.p21 is a universal inhibitor of cyclin kinases . Nature , 366 , 701 – 704 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Waga , S. , Hannon , G. J. , Beach , D. and Stillman , B.The p21 inhibitor of cyclin‐dependence kinases controls DNA replication by interaction with PCNA . Nature , 369 , 574 – 578 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Shimizu , T. , Miwa , W. , Nakamori , S. , Ishikawa , O. , Konishi , Y. and Sekiya , T.Absence of a mutation of the p21/WAF1 gene in human lung and pancreatic cancers . Jpn. J. Cancer Res. , 87 , 275 – 278 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Shiohara , M. , El‐Deiry , W. S. , Wada , M. , Nakamaki , T. , Takeuchi , S. , Yang , R. , Chen , D.‐L. , Vogelstein , B. and Koeffler , P.Absence of WAF1 mutations in a variety of human malignancies . Blood , 84 , 3781 – 3784 ( 1994. ). [PubMed] [Google Scholar]
  • 7. ) Koopmann , J. , Maintz , D. , Schild , S. , Schramm , J. , Louis , D. N. , Wiestler , O. D. and von Deimling , A.Multiple polymorphisms, but no mutations, in the WAF1/CIP1 gene in human brain tumours . Br. J. Cancer , 72 , 1231 – 1233 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Chedid , M. , Michieli , P. , Lengel , C. , Huppi , K. and Givol , D.A. A single nucleotide substitution at codon 31 (Ser/Arg) defines a polymorphism in a highly conserved region of the p53‐inducible gene WAF1/CIP1 . Oncogene , 9 , 3021 – 3024 ( 1994. ). [PubMed] [Google Scholar]
  • 9. ) Huppi , K. , Siwarski , D. , Dosik , J. , Michieli , P. , Chedid , M. , Reed , S. , Mock , B. , Givol , D. and Mushinsky , J. F.Molecular cloning, sequencing, chromosomal localization and expression of mouse p21 (WAF) . Oncogene , 9 , 3017 – 3020 ( 1994. ). [PubMed] [Google Scholar]
  • 10. ) Lori , A. T. , Boyd , J. , Alcorta , D. , Lyon , T. , Solomon , G. , Hannon , G. , Berchuck , A. , Beach , D. and Barrett , J. C.Mutational analysis of the p21/WAF1/CIP1/SID1 coding region in human tumor cell lines . Mol. Carcinog. , 16 , 221 – 228 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Sun , Y. , Hildesheim , A. , Li , H. , Li , Y. , Chen , J.‐Y. , Cheng , Y.‐J. , Hayes , R. B. , Rothman , N. , Bi , W.‐F. , Cao , Y. , Yao , K.‐T. , Lanier , A. P. , Hegamyer , G. , El‐Deiry , W. S. , Xiong , Y. and Colburn , N. H.No point mutation but a codon 31ser→arg polymorphism of the WAF‐1/CIP‐1/p21 tumor suppressor gene in nasopharyngeal carcinoma (NPC): the polymorphism distinguishes Caucasians from Chinese . Cancer Epidemiol. Biomarkers Prev. , 4 , 261 – 267 ( 1995. ). [PubMed] [Google Scholar]
  • 12. ) Mousses , S. , Ozcelik , H. , Lee , P. D. , Malkin , D. , Bull , S. B. and Andrulis , I. L.Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer . Hum. Mol. Genet. , 4 , 1089 – 1092 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Akama , Y. , Yasui , W. , Kuniyasu , H. , Yokozaki , H. , Akagi , M. and Tahara , H.No point mutations but a codon 31 polymorphism and decreased expression of the p21(SDI1/WAF1/CIP1/MDA6) gene in human gastric carcinomas . Mol. Cell Differ. , 4 , 187 – 198 ( 1996. ). [Google Scholar]
  • 14. ) Hachiya , T. , Kuriaki , Y. , Ueoka , Y. , Nishida , J. , Kato , K. and Wake , N.WAF1 genotype and endometrial cancer susceptibility . Gynecol. Oncol. , 72 , 187 – 192 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Själander , A. , Birgander , R. , Rannug , A. , Alexandrie , A. K. , Tornling , G. and Beckman , G.Association between the p21 codon 31 A1 (arg) allele and lung cancer . Hum. Hered. , 46 , 221 – 225 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Facher , E. A. , Becich , M. J. , Deka , A. and Law , J. C.Association between human cancer and two polymorphisms occurring together in the p21Waf1/Cip1 cyclin‐dependent kinase inhibitor gene . Cancer , 79 , 2424 – 2429 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Heinzel , P. A. , Balaram , P. and Bernard , H.‐U.Mutations and polymorphisms in the p53, p21 and p16 genes in oral carcinomas of Indian betal quid chewers . Int. J. Cancer , 68 , 420 – 423 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Lukas , J. , Groshen , S. , Saffari , B. , Niu , N. , Reles , A. , Wen , W.‐H. , Felix , J. , Jones , L. A. , Hall , F. L. and Press , M. F.WAF1/CIP1 gene polymorphism and expression in carcinomas of the breast, ovary, and endometrium . Am. J. Pathol. , 150 , 167 – 175 ( 1997. ). [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Milner , B. J. , Hosking , L. , Sun , S. , Haites , N. E. and Foulkes , W. D.Polymorphisms in p21CIP1/WAF1 are not correlated with TP53 status in sporadic ovarian tumours . Eur. J. Cancer , 32A , 2360 – 2363 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Birgander , R. , Själander , A. , Saha , N. , Spitsyn , V. , Beckman L. and Beckman , G.The codon 31 polymorphism of the p53‐inducible gene p21 shows distinct differences between major ethnic groups . Hum. Hered. , 46 , 148 – 154 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) WHO. Histological typing of lung tumors . Am. J. Clin. Pathol. , 77 , 123 – 126 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Mountain , C. F.A new international staging system for lung cancer . Chest , 89 , 225 – 233 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Lehman , T. A. , Bennett , W. P. , Metcalf , R. A. , Welsh , J. A. , Ecker , J. , Modali , R. V. , Ullrich , S. , Romano , J. W. , Appella , E. , Testa , J. R. , Gerwin , B. I. and Harris , C. C.p53 mutations, ras mutations, and p53‐heat shock 70 protein complexes in human lung carcinoma cell lines . Cancer Res. , 51 , 4090 – 4096 ( 1991. ). [PubMed] [Google Scholar]
  • 24. ) Lee , E. T. “ Statistical Methods for Survival Data Analysis ,” 2nd Ed. , pp. 1 – 7 ( 1992. ). John Wiley & Sons, Inc. , New York . [Google Scholar]
  • 25. ) Kaplan , E. L. and Meier , P.Nonparametric estimation from incomplete observation . J. Am. Stat. Assoc. , 53 , 457 – 481 ( 1958. ). [Google Scholar]
  • 26. ) The Lifetest Procedure . In “ SAS Technical Report: P‐179 ,” Additional SAS/STAT Procedures, Release 6.03 , pp. 49 – 90 ( 1988. ). SAS Institute; , Cary , NC . [Google Scholar]
  • 27. ) Wang , Y.‐C. , Chen , C.‐Y. , Chen , S.‐K. , Chang , Y.‐Y. and Pin , L.p53 codon 73 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis . Clin. Cancer Res. , 5 , 129 – 134 ( 1999. ). [PubMed] [Google Scholar]
  • 28. ) Wang , Y.‐C. , Chen , C.‐Y. , Chen , S.‐K. , Cherng , S.‐H. , Ho , W. L. and Lee , H.High frequency of deletion mutations in p53 gene from squamous‐cell lung cancer patients in Taiwan . Cancer Res. , 58 , 328 – 333 ( 1998. ). [PubMed] [Google Scholar]
  • 29. ) Beckman , G. , Birgander , R. , Själander , A. , Saha , N. , Holmberg , P. Å. , Kivelä , A. and Beckman , L.Is p53 polymorphism maintained by natural selection ? Hum. Hered. , 44 , 266 – 270 ( 1994. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES