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. 1996 Apr;73(8):902–908. doi: 10.1038/bjc.1996.180

The relationship between smoking exposure and p53 overexpression in colorectal cancer.

A N Freedman 1, A M Michalek 1, J R Marshall 1, C J Mettlin 1, N J Petrelli 1, Z F Zhang 1, J D Black 1, S Satchidanand 1, J E Asirwatham 1
PMCID: PMC2075827  PMID: 8611424

Abstract

Although epidemiological studies of the relationship between cigarette smoking and colorectal cancer risk have been equivocal, a positive association is consistently found for colorectal adenoma development. We performed an epidemiological study to determine whether p53 protein overexpression, in tumours obtained at the time of resection, is associated with cigarette exposure in colorectal cancer. A total of 163 colorectal cancer cases and 326 healthy controls responded to a standardised questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking. All patients' tumours were analysed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Comparison of colorectal cases with controls revealed an elevated risk for ex-smokers (OR = 1.34, 95% CI 0.85-2.12) and current smokers (OR = 1.13, 95% CI 0.63-2.02) when compared with non-smokers. No dose-response relationship was found for total pack-years of smoking (trend test: P = 0.19). However, a trend for total pack-years of smoking was found when p53-positive cases were compared with p53-negative cases suggesting aetiological, heterogeneity (trend test: P = 0.06). Estimating the individual relative risk of developing a p53-positive tumour relative to controls showed no associations for smoking status or total pack-years of smoking. However, when p53-negative cases were compared with controls, an elevated risk was found for ex-smokers (OR = 1.84, 95% CI 1.00-3.37) and current years of smoking (trend test: P = 0.03). Colorectal tumours developing through p53-positive dependent pathways were not associated with smoking exposure. A significant increase in risk was observed for the p53-negative independent pathway with smoking. p53 overexpression appears to be associated with smoking exposure in colorectal cancer.

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Selected References

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  1. Begg C. B., Zhang Z. F. Statistical analysis of molecular epidemiology studies employing case-series. Cancer Epidemiol Biomarkers Prev. 1994 Mar;3(2):173–175. [PubMed] [Google Scholar]
  2. Bennett W. P., Hollstein M. C., He A., Zhu S. M., Resau J. H., Trump B. F., Metcalf R. A., Welsh J. A., Midgley C., Lane D. P. Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. Oncogene. 1991 Oct;6(10):1779–1784. [PubMed] [Google Scholar]
  3. Carstensen J. M., Pershagen G., Eklund G. Mortality in relation to cigarette and pipe smoking: 16 years' observation of 25,000 Swedish men. J Epidemiol Community Health. 1987 Jun;41(2):166–172. doi: 10.1136/jech.41.2.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chiba I., Takahashi T., Nau M. M., D'Amico D., Curiel D. T., Mitsudomi T., Buchhagen D. L., Carbone D., Piantadosi S., Koga H. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603–1610. [PubMed] [Google Scholar]
  5. Choi S. Y., Kahyo H. Effect of cigarette smoking and alcohol consumption in the etiology of cancers of the digestive tract. Int J Cancer. 1991 Sep 30;49(3):381–386. doi: 10.1002/ijc.2910490312. [DOI] [PubMed] [Google Scholar]
  6. Chute C. G., Willett W. C., Colditz G. A., Stampfer M. J., Baron J. A., Rosner B., Speizer F. E. A prospective study of body mass, height, and smoking on the risk of colorectal cancer in women. Cancer Causes Control. 1991 Mar;2(2):117–124. doi: 10.1007/BF00053131. [DOI] [PubMed] [Google Scholar]
  7. Cope G. F., Wyatt J. I., Pinder I. F., Lee P. N., Heatley R. V., Kelleher J. Alcohol consumption in patients with colorectal adenomatous polyps. Gut. 1991 Jan;32(1):70–72. doi: 10.1136/gut.32.1.70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cordon-Cardo C., Dalbagni G., Saez G. T., Oliva M. R., Zhang Z. F., Rosai J., Reuter V. E., Pellicer A. p53 mutations in human bladder cancer: genotypic versus phenotypic patterns. Int J Cancer. 1994 Feb 1;56(3):347–353. doi: 10.1002/ijc.2910560309. [DOI] [PubMed] [Google Scholar]
  9. Dales L. G., Friedman G. D., Ury H. K., Grossman S., Williams S. R. A case-control study of relationships of diet and other traits to colorectal cancer in American blacks. Am J Epidemiol. 1979 Feb;109(2):132–144. doi: 10.1093/oxfordjournals.aje.a112668. [DOI] [PubMed] [Google Scholar]
  10. Demers R. Y., Neale A. V., Demers P., Deighton K., Scott R. O., Dupuis M. H., Herman S. Serum cholesterol and colorectal polyps. J Clin Epidemiol. 1988;41(1):9–13. doi: 10.1016/0895-4356(88)90003-0. [DOI] [PubMed] [Google Scholar]
  11. Doll R., Gray R., Hafner B., Peto R. Mortality in relation to smoking: 22 years' observations on female British doctors. Br Med J. 1980 Apr 5;280(6219):967–971. doi: 10.1136/bmj.280.6219.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Doll R., Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J. 1976 Dec 25;2(6051):1525–1536. doi: 10.1136/bmj.2.6051.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Drexler J. Asymptomatic polyps of the colon and rectum. 3. Proximal and distal polyp relationships. Arch Intern Med. 1971 Mar;127(3):466–469. [PubMed] [Google Scholar]
  14. Fearon E. R. Molecular genetic studies of the adenoma-carcinoma sequence. Adv Intern Med. 1994;39:123–147. [PubMed] [Google Scholar]
  15. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  16. Ferraroni M., Negri E., La Vecchia C., D'Avanzo B., Franceschi S. Socioeconomic indicators, tobacco and alcohol in the aetiology of digestive tract neoplasms. Int J Epidemiol. 1989 Sep;18(3):556–562. doi: 10.1093/ije/18.3.556. [DOI] [PubMed] [Google Scholar]
  17. Field J. K., Spandidos D. A., Malliri A., Gosney J. R., Yiagnisis M., Stell P. M. Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck. Br J Cancer. 1991 Sep;64(3):573–577. doi: 10.1038/bjc.1991.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Field J. K., Zoumpourlis V., Spandidos D. A., Jones A. S. p53 expression and mutations in squamous cell carcinoma of the head and neck: expression correlates with the patients' use of tobacco and alcohol. Cancer Detect Prev. 1994;18(3):197–208. [PubMed] [Google Scholar]
  19. Garland C., Shekelle R. B., Barrett-Connor E., Criqui M. H., Rossof A. H., Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985 Feb 9;1(8424):307–309. doi: 10.1016/s0140-6736(85)91082-7. [DOI] [PubMed] [Google Scholar]
  20. Giovannucci E., Colditz G. A., Stampfer M. J., Hunter D., Rosner B. A., Willett W. C., Speizer F. E. A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. women. J Natl Cancer Inst. 1994 Feb 2;86(3):192–199. doi: 10.1093/jnci/86.3.192. [DOI] [PubMed] [Google Scholar]
  21. Giovannucci E., Rimm E. B., Stampfer M. J., Colditz G. A., Ascherio A., Kearney J., Willett W. C. A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. men. J Natl Cancer Inst. 1994 Feb 2;86(3):183–191. doi: 10.1093/jnci/86.3.183. [DOI] [PubMed] [Google Scholar]
  22. Graham S., Dayal H., Swanson M., Mittelman A., Wilkinson G. Diet in the epidemiology of cancer of the colon and rectum. J Natl Cancer Inst. 1978 Sep;61(3):709–714. [PubMed] [Google Scholar]
  23. Greenblatt M. S., Bennett W. P., Hollstein M., Harris C. C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994 Sep 15;54(18):4855–4878. [PubMed] [Google Scholar]
  24. Haenszel W., Berg J. W., Segi M., Kurihara M., Locke F. B. Large-bowel cancer in Hawaiian Japanese. J Natl Cancer Inst. 1973 Dec;51(6):1765–1779. doi: 10.1093/jnci/51.6.1765. [DOI] [PubMed] [Google Scholar]
  25. Haenszel W., Locke F. B., Segi M. A case-control study of large bowel cancer in Japan. J Natl Cancer Inst. 1980 Jan;64(1):17–22. [PubMed] [Google Scholar]
  26. Hammond E. C., Horn D. Smoking and death rates: report on forty-four months of follow-up of 187,783 men. 2. Death rates by cause. J Am Med Assoc. 1958 Mar 15;166(11):1294–1308. doi: 10.1001/jama.1958.02990110030007. [DOI] [PubMed] [Google Scholar]
  27. Hammond E. C. Smoking in relation to the death rates of one million men and women. Natl Cancer Inst Monogr. 1966 Jan;19:127–204. [PubMed] [Google Scholar]
  28. Harris C. C. Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res. 1991 Sep 15;51(18 Suppl):5023s–5044s. [PubMed] [Google Scholar]
  29. Heineman E. F., Zahm S. H., McLaughlin J. K., Vaught J. B. Increased risk of colorectal cancer among smokers: results of a 26-year follow-up of US veterans and a review. Int J Cancer. 1994 Dec 15;59(6):728–738. doi: 10.1002/ijc.2910590603. [DOI] [PubMed] [Google Scholar]
  30. Higginson J. Etiological factors in gastrointestinal cancer in man. J Natl Cancer Inst. 1966 Oct;37(4):527–545. [PubMed] [Google Scholar]
  31. Hoff G., Vatn M. H., Larsen S. Relationship between tobacco smoking and colorectal polyps. Scand J Gastroenterol. 1987 Jan;22(1):13–16. doi: 10.3109/00365528708991849. [DOI] [PubMed] [Google Scholar]
  32. Hollstein M. C., Peri L., Mandard A. M., Welsh J. A., Montesano R., Metcalf R. A., Bak M., Harris C. C. Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. Cancer Res. 1991 Aug 1;51(15):4102–4106. [PubMed] [Google Scholar]
  33. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  34. Honjo S., Kono S., Shinchi K., Imanishi K., Hirohata T. Cigarette smoking, alcohol use and adenomatous polyps of the sigmoid colon. Jpn J Cancer Res. 1992 Aug;83(8):806–811. doi: 10.1111/j.1349-7006.1992.tb01984.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jain M., Cook G. M., Davis F. G., Grace M. G., Howe G. R., Miller A. B. A case-control study of diet and colo-rectal cancer. Int J Cancer. 1980 Dec 15;26(6):757–768. doi: 10.1002/ijc.2910260609. [DOI] [PubMed] [Google Scholar]
  36. Jarebinski M., Adanja B., Vlajinac H. Case-control study of relationship of some biosocial correlates to rectal cancer patients in Belgrade, Yugoslavia. Neoplasma. 1989;36(3):369–374. [PubMed] [Google Scholar]
  37. Jarebinski M., Vlajinac H., Adanja B. Biosocial and other characteristics of the large bowel cancer patients in Belgrade (Yugoslavia). Arch Geschwulstforsch. 1988;58(6):411–417. [PubMed] [Google Scholar]
  38. Jones P. A., Buckley J. D., Henderson B. E., Ross R. K., Pike M. C. From gene to carcinogen: a rapidly evolving field in molecular epidemiology. Cancer Res. 1991 Jul 1;51(13):3617–3620. [PubMed] [Google Scholar]
  39. Kabat G. C., Howson C. P., Wynder E. L. Beer consumption and rectal cancer. Int J Epidemiol. 1986 Dec;15(4):494–501. doi: 10.1093/ije/15.4.494. [DOI] [PubMed] [Google Scholar]
  40. Klatsky A. L., Armstrong M. A., Friedman G. D., Hiatt R. A. The relations of alcoholic beverage use to colon and rectal cancer. Am J Epidemiol. 1988 Nov;128(5):1007–1015. doi: 10.1093/oxfordjournals.aje.a115045. [DOI] [PubMed] [Google Scholar]
  41. Kono S., Ikeda M., Tokudome S., Nishizumi M., Kuratsune M. Cigarette smoking, alcohol and cancer mortality: a cohort study of male Japanese physicians. Jpn J Cancer Res. 1987 Dec;78(12):1323–1328. [PubMed] [Google Scholar]
  42. Kune G. A., Kune S., Vitetta L., Watson L. F. Smoking and colorectal cancer risk: data from the Melbourne Colorectal Cancer Study and brief review of literature. Int J Cancer. 1992 Feb 1;50(3):369–372. doi: 10.1002/ijc.2910500307. [DOI] [PubMed] [Google Scholar]
  43. Kune G. A., Kune S., Watson L. F., Penfold C. Smoking and adenomatous colorectal polyps. Gastroenterology. 1992 Oct;103(4):1370–1371. doi: 10.1016/0016-5085(92)91545-f. [DOI] [PubMed] [Google Scholar]
  44. Layton D. W., Bogen K. T., Knize M. G., Hatch F. T., Johnson V. M., Felton J. S. Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research. Carcinogenesis. 1995 Jan;16(1):39–52. doi: 10.1093/carcin/16.1.39. [DOI] [PubMed] [Google Scholar]
  45. Lee W. C., Neugut A. I., Garbowski G. C., Forde K. A., Treat M. R., Waye J. D., Fenoglio-Preiser C. Cigarettes, alcohol, coffee, and caffeine as risk factors for colorectal adenomatous polyps. Ann Epidemiol. 1993 May;3(3):239–244. doi: 10.1016/1047-2797(93)90025-y. [DOI] [PubMed] [Google Scholar]
  46. Martínez M. E., McPherson R. S., Annegers J. F., Levin B. Cigarette smoking and alcohol consumption as risk factors for colorectal adenomatous polyps. J Natl Cancer Inst. 1995 Feb 15;87(4):274–279. doi: 10.1093/jnci/87.4.274. [DOI] [PubMed] [Google Scholar]
  47. Miller C. W., Simon K., Aslo A., Kok K., Yokota J., Buys C. H., Terada M., Koeffler H. P. p53 mutations in human lung tumors. Cancer Res. 1992 Apr 1;52(7):1695–1698. [PubMed] [Google Scholar]
  48. Monnet E., Allemand H., Farina H., Carayon P. Cigarette smoking and the risk of colorectal adenoma in men. Scand J Gastroenterol. 1991 Jul;26(7):758–762. doi: 10.3109/00365529108998596. [DOI] [PubMed] [Google Scholar]
  49. Olsen J., Kronborg O. Coffee, tobacco and alcohol as risk factors for cancer and adenoma of the large intestine. Int J Epidemiol. 1993 Jun;22(3):398–402. doi: 10.1093/ije/22.3.398. [DOI] [PubMed] [Google Scholar]
  50. Papadimitriou C., Day N., Tzonou A., Gerovassilis F., Manousos O., Trichopoulos D. Biosocial correlates of colorectal cancer in Greece. Int J Epidemiol. 1984 Jun;13(2):155–159. doi: 10.1093/ije/13.2.155. [DOI] [PubMed] [Google Scholar]
  51. Peters R. K., Garabrant D. H., Yu M. C., Mack T. M. A case-control study of occupational and dietary factors in colorectal cancer in young men by subsite. Cancer Res. 1989 Oct 1;49(19):5459–5468. [PubMed] [Google Scholar]
  52. Rogot E., Murray J. L. Smoking and causes of death among U.S. veterans: 16 years of observation. Public Health Rep. 1980 May-Jun;95(3):213–222. [PMC free article] [PubMed] [Google Scholar]
  53. Sandler R. S., Lyles C. M., McAuliffe C., Woosley J. T., Kupper L. L. Cigarette smoking, alcohol, and the risk of colorectal adenomas. Gastroenterology. 1993 May;104(5):1445–1451. doi: 10.1016/0016-5085(93)90354-f. [DOI] [PubMed] [Google Scholar]
  54. Sandler R. S., Sandler D. P., Comstock G. W., Helsing K. J., Shore D. L. Cigarette smoking and the risk of colorectal cancer in women. J Natl Cancer Inst. 1988 Oct 19;80(16):1329–1333. doi: 10.1093/jnci/80.16.1329. [DOI] [PubMed] [Google Scholar]
  55. Shi S. R., Key M. E., Kalra K. L. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. doi: 10.1177/39.6.1709656. [DOI] [PubMed] [Google Scholar]
  56. Spruck C. H., 3rd, Rideout W. M., 3rd, Olumi A. F., Ohneseit P. F., Yang A. S., Tsai Y. C., Nichols P. W., Horn T., Hermann G. G., Steven K. Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage. Cancer Res. 1993 Mar 1;53(5):1162–1166. [PubMed] [Google Scholar]
  57. Subar A. F., Harlan L. C. Nutrient and food group intake by tobacco use status: the 1987 National Health Interview Survey. Ann N Y Acad Sci. 1993 May 28;686:310–322. doi: 10.1111/j.1749-6632.1993.tb39193.x. [DOI] [PubMed] [Google Scholar]
  58. Suzuki H., Takahashi T., Kuroishi T., Suyama M., Ariyoshi Y., Takahashi T., Ueda R. p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. Cancer Res. 1992 Feb 1;52(3):734–736. [PubMed] [Google Scholar]
  59. Tajima K., Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan. Jpn J Cancer Res. 1985 Aug;76(8):705–716. [PubMed] [Google Scholar]
  60. Tuyns A. J., Péquignot G., Gignoux M., Valla A. Cancers of the digestive tract, alcohol and tobacco. Int J Cancer. 1982 Jul 15;30(1):9–11. doi: 10.1002/ijc.2910300103. [DOI] [PubMed] [Google Scholar]
  61. Tverdal A., Thelle D., Stensvold I., Leren P., Bjartveit K. Mortality in relation to smoking history: 13 years' follow-up of 68,000 Norwegian men and women 35-49 years. J Clin Epidemiol. 1993 May;46(5):475–487. doi: 10.1016/0895-4356(93)90025-v. [DOI] [PubMed] [Google Scholar]
  62. Umekita Y., Kobayashi K., Saheki T., Yoshida H. Nuclear accumulation of p53 protein correlates with mutations in the p53 gene on archival paraffin-embedded tissues of human breast cancer. Jpn J Cancer Res. 1994 Aug;85(8):825–830. doi: 10.1111/j.1349-7006.1994.tb02954.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Vobecky J., Caro J., Devroede G. A case-control study of risk factors for large bowel carcinoma. Cancer. 1983 May 15;51(10):1958–1963. doi: 10.1002/1097-0142(19830515)51:10<1958::aid-cncr2820511036>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  64. Weir J. M., Dunn J. E., Jr Smoking and mortality: a prospective study. Cancer. 1970 Jan;25(1):105–112. doi: 10.1002/1097-0142(197001)25:1<105::aid-cncr2820250115>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  65. Williams R. R., Horm J. W. Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J Natl Cancer Inst. 1977 Mar;58(3):525–547. doi: 10.1093/jnci/58.3.525. [DOI] [PubMed] [Google Scholar]
  66. Williams R. R., Sorlie P. D., Feinleib M., McNamara P. M., Kannel W. B., Dawber T. R. Cancer incidence by levels of cholesterol. JAMA. 1981 Jan 16;245(3):247–252. [PubMed] [Google Scholar]
  67. Wu A. H., Paganini-Hill A., Ross R. K., Henderson B. E. Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study. Br J Cancer. 1987 Jun;55(6):687–694. doi: 10.1038/bjc.1987.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wynder E. L., Kajitani T., Ishikawa S., Dodo H., Takano A. Environmental factors of cancer of the colon and rectum. II. Japanese epidemiological data. Cancer. 1969 May;23(5):1210–1220. doi: 10.1002/1097-0142(196905)23:5<1210::aid-cncr2820230530>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  69. Wynder E. L., Shigematsu T. Environmental factors of cancer of the colon and rectum. Cancer. 1967 Sep;20(9):1520–1561. doi: 10.1002/1097-0142(196709)20:9<1520::aid-cncr2820200920>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  70. Zahm S. H., Cocco P., Blair A. Tobacco smoking as a risk factor for colon polyps. Am J Public Health. 1991 Jul;81(7):846–849. doi: 10.2105/ajph.81.7.846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Zhang Z. F., Sarkis A. S., Cordon-Cardo C., Dalbagni G., Melamed J., Aprikian A., Pollack D., Sheinfeld J., Herr H. W., Fair W. R. Tobacco smoking, occupation, and p53 nuclear overexpression in early stage bladder cancer. Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):19–24. [PubMed] [Google Scholar]
  72. Zhang Z. F., Zeng Z. S., Sarkis A. S., Klimstra D. S., Charytonowicz E., Pollack D., Vena J., Guillem J., Marshall J. R., Cordon-Cardo C. Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer. Br J Cancer. 1995 Apr;71(4):888–893. doi: 10.1038/bjc.1995.171. [DOI] [PMC free article] [PubMed] [Google Scholar]

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