Cancer Causes & Control

, Volume 19, Issue 7, pp 689–701 | Cite as

Smoking and gastric cancer: systematic review and meta-analysis of cohort studies

  • Ricardo Ladeiras-Lopes
  • Alexandre Kirchhofer Pereira
  • Amanda Nogueira
  • Tiago Pinheiro-Torres
  • Isabel Pinto
  • Ricardo Santos-Pereira
  • Nuno LunetEmail author
Original Paper



We conducted a systematic review of studies addressing the relation between cigarette smoking and gastric cancer to estimate the magnitude of the association for different levels of exposure and cancer locations.


Published cohort, case–cohort, and nested case–control studies were identified through PubMed, Scopus, and Web of Science searches, from inception to July 2007. Relative risk (RR) estimates referring to the comparison of two categories of exposure (e.g., current smokers vs. never smokers) were combined using a random effects model. Generalized least squares regression was used for trend estimation. Heterogeneity was quantified using the I 2 statistic.


Forty-two articles were considered for the systematic review. Comparing current smokers with never smokers: the summary RR estimates were 1.62 in males (95% CI: 1.50–1.75; I 2 = 46.0%; 18 studies) and 1.20 in females (95% CI: 1.01–1.43; I 2 = 49.8%; nine studies); the RR increased from 1.3 for the lowest consumptions to 1.7 for the smoking of approximately 30 cigarettes per day in the trend estimation analysis; smoking was significantly associated with both cardia (RR = 1.87; 95% CI: 1.31–2.67; I 2 = 73.2%; nine studies) and non-cardia (RR = 1.60; 95% CI: 1.41–1.80; I 2 = 18.9%; nine studies) cancers.


Our study provides solid evidence to classify smoking as the most important behavioral risk factor for gastric cancer.


Stomach neoplasms Smoking Meta-analysis Cohort studies 


  1. 1.
    Tredaniel J, Boffetta P, Buiatti E et al (1997) Tobacco smoking and gastric cancer: review and meta-analysis. Int J Cancer 72:565–573PubMedCrossRefGoogle Scholar
  2. 2.
    International Agency for Research on Cancer (2004) Tobacco smoke and involuntary smoking. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol. 83. IARC, LyonGoogle Scholar
  3. 3.
    World Cancer Research Fund (1997) Food, nutrition and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington, DCGoogle Scholar
  4. 4.
    Lunet N, Lacerda-Vieira A, Barros H (2005) Fruit and vegetables consumption and gastric cancer: a systematic review and meta-analysis of cohort studies. Nutr Cancer 53:1–10PubMedCrossRefGoogle Scholar
  5. 5.
    International Agency for Research on Cancer. Schistosomes, liver flukes and Helicobacter pylori. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol. 61. IARC, LyonGoogle Scholar
  6. 6.
    Nishino Y, Inoue M, Tsuji I et al (2006) Tobacco smoking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 36:800–807PubMedCrossRefGoogle Scholar
  7. 7.
    Greenland S, Longnecker M (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309PubMedGoogle Scholar
  8. 8.
    Higgins J, Thompson S (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  9. 9.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRefGoogle Scholar
  10. 10.
    Egger M, Smith GD, Schieder M, Minder C (1997) Bias in meta-analysis detected by a simple graphical test. BMJ 315:629–634PubMedGoogle Scholar
  11. 11.
    Guo W, Blot WJ, Li JY et al (1994) A nested case–control study of oesophageal and stomach cancers in the Linxian nutrition intervention trial. Int J Epidemiol 23:444–450PubMedCrossRefGoogle Scholar
  12. 12.
    Kato I, Tominaga S, Ito Y et al (1992) A prospective study of atrophic gastritis and stomach cancer risk. Jpn J Cancer Res 83:1137–1142PubMedGoogle Scholar
  13. 13.
    Nomura A, Grove JS, Stemmermann GN, Severson RK (1990) A prospective study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption. Cancer Res 50:627–631PubMedGoogle Scholar
  14. 14.
    Abnet CC, Qiao YL, Mark SD et al (2001) Prospective study of tooth loss and incident esophageal and gastric cancers in China. Cancer Causes Control 12:847–854PubMedCrossRefGoogle Scholar
  15. 15.
    Yun YH, Jung KW, Bae JM et al (2005) Cigarette smoking and cancer incidence risk in adult men: National Health Insurance Corporation Study. Cancer Detect Prev 29:15–24PubMedCrossRefGoogle Scholar
  16. 16.
    Liaw KM, Chen CJ (1998) Mortality attributable to cigarette smoking in Taiwan: a 12-year follow-up study. Tob Control 7:141–148PubMedGoogle Scholar
  17. 17.
    Tran GD, Sun XD, Abnet CC et al (2005) Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer 113:456–463PubMedCrossRefGoogle Scholar
  18. 18.
    Inoue M, Tajima K, Kobayashi S et al (1996) Protective factor against progression from atrophic gastritis to gastric cancer—data from a cohort study in Japan. Int J Cancer 66:309–314PubMedCrossRefGoogle Scholar
  19. 19.
    Nomura AM, Stemmermann GN, Chyou PH (1995) Gastric cancer among the Japanese in Hawaii. Jpn J Cancer Res 86:916–923PubMedGoogle Scholar
  20. 20.
    Wen CP, Tsai SP, Chen CJ, Cheng TY (2004) The mortality risks of smokers in Taiwan—Part I: cause-specific mortality. Prev Med 39:528–535PubMedCrossRefGoogle Scholar
  21. 21.
    Doll R, Peto R, Boreham J, Sutherland I (2005) Mortality from cancer in relation to smoking: 50 years observations on British doctors. Br J Cancer 92:426–429PubMedCrossRefGoogle Scholar
  22. 22.
    Doll R, Peto R (1976) Mortality in relation to smoking: 20 years’ observations on male British doctors. Br Med J 2:1525–1536PubMedGoogle Scholar
  23. 23.
    Doll R, Peto R, Wheatley K et al (1994) Mortality in relation to smoking: 40 years’ observations on male British doctors. Br Med J 309:901–911Google Scholar
  24. 24.
    McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JF Jr (1990) Stomach cancer and cigarette smoking among U.S. veterans, 1954–1980. Cancer Res 50:3804PubMedGoogle Scholar
  25. 25.
    Kahn HA (1966) The Dorn study of smoking and mortality among U.S. veterans: report on eight and one-half years of observation. Natl Cancer Inst Monogr 19:1–125PubMedGoogle Scholar
  26. 26.
    Mizoue T, Tokui N, Nishisaka K et al (2000) Prospective study on the relation of cigarette smoking with cancer of the liver and stomach in an endemic region. Int J Epidemiol 29:232–237PubMedCrossRefGoogle Scholar
  27. 27.
    Ngoan LT, Mizoue T, Fujino Y et al (2002) Dietary factors and stomach cancer mortality. Br J Cancer 87:37–42PubMedCrossRefGoogle Scholar
  28. 28.
    McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JF Jr (1995) Smoking and cancer mortality among U.S. veterans: a 26-year follow-up. Int J Cancer 60:190–193PubMedGoogle Scholar
  29. 29.
    Blair A, Walrath J, Rogot E (1985) Mortality patterns among U.S. veterans by occupation. I. Cancer. J Natl Cancer Inst 75:1039–1047PubMedGoogle Scholar
  30. 30.
    Sung NY, Choi KS, Park EC et al (2007) Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study. Br J Cancer 97:700–704PubMedCrossRefGoogle Scholar
  31. 31.
    Hammond EC, Horn D (1958) 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 166:1294–1308Google Scholar
  32. 32.
    Freedman ND, Chow WH, Gao YT et al (2007) Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women. Gut 56:1671–1677PubMedCrossRefGoogle Scholar
  33. 33.
    Wong BC, Lam SK, Wong WM et al (2004) Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 291:187–194PubMedCrossRefGoogle Scholar
  34. 34.
    Terry P, Nyren O, Yuen J (1998) Protective effect of fruits and vegetables on stomach cancer in a cohort of Swedish twins. Int J Cancer 76:35–37PubMedCrossRefGoogle Scholar
  35. 35.
    Hammond EC (1966) Smoking in relation to the death rates of one million men and women. Natl Cancer Inst Monogr 19:127–204PubMedGoogle Scholar
  36. 36.
    Weir JM, Dunn JE Jr (1970) Smoking and mortality: a prospective study. Cancer 25:105–112PubMedCrossRefGoogle Scholar
  37. 37.
    Yuan JM, Ross RK, Wang XL et al (1996) Morbidity and mortality in relation to cigarette smoking in Shanghai, China. A prospective male cohort study. JAMA 275:1646–1650PubMedCrossRefGoogle Scholar
  38. 38.
    Carstensen JM, Pershagen G, Eklund G (1987) Mortality in relation to cigarette and pipe smoking: 16 years’ observation of 25,000 Swedish men. J Epidemiol Community Health 41:166–172PubMedCrossRefGoogle Scholar
  39. 39.
    Kasum CM, Jacobs Jr DR, Nicodemus K, Folsom AR (2002) Dietary risk factors for upper aerodigestive tract cancers. Int J Cancer 99:267–272PubMedCrossRefGoogle Scholar
  40. 40.
    Kurosawa M, Kikuchi S, Xu J, Inaba Y (2006) Highly salted food and mountain herbs elevate the risk for stomach cancer death in a rural area of Japan. J Gastroenterol Hepatol 21:1681–1686PubMedCrossRefGoogle Scholar
  41. 41.
    Sauvaget C, Lagarde F, Nagano J et al (2005) Lifestyle factors, radiation and gastric cancer in atomic-bomb survivors (Japan). Cancer Causes Control 16:773–780PubMedCrossRefGoogle Scholar
  42. 42.
    Fujino Y, Mizoue T, Tokui N et al (2005) Cigarette smoking and mortality due to stomach cancer: findings from the JACC Study. J Epidemiol 15(Suppl 2):S113–119PubMedCrossRefGoogle Scholar
  43. 43.
    Koizumi Y, Tsubono Y, Nakaya N et al (2004) Cigarette smoking and the risk of gastric cancer: a pooled analysis of two prospective studies in Japan. Int J Cancer 112:1049–1055PubMedCrossRefGoogle Scholar
  44. 44.
    Sasazuki S, Sasaki S, Tsugane S (2002) Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by subsite and histologic type. Int J Cancer 101:560–566PubMedCrossRefGoogle Scholar
  45. 45.
    Murata M, Takayama K, Choi BC, Pak AW (1996) A nested case–control study on alcohol drinking, tobacco smoking, and cancer. Cancer Detect Prev 20:557–565PubMedGoogle Scholar
  46. 46.
    Xu Z, Brown LM, Pan GW et al (1996) Cancer risks among iron and steel workers in Anshan, China, Part II: case–control studies of lung and stomach cancer. Am J Ind Med 30:7–15PubMedCrossRefGoogle Scholar
  47. 47.
    Kato I, Tominaga S, Matsumoto K (1992) A prospective study of stomach cancer among a rural Japanese population: a 6-year survey. Jpn J Cancer Res 83:568–575PubMedGoogle Scholar
  48. 48.
    Akiba S, Hirayama T (1990) Cigarette smoking and cancer mortality risk in Japanese men and women—results from reanalysis of the six-prefecture cohort study data. Environ Health Perspect 87:19–26PubMedCrossRefGoogle Scholar
  49. 49.
    Kono S, Ikeda M, Tokudome S et al (1987) Cigarette smoking, alcohol and cancer mortality: a cohort study of male Japanese physicians. Jpn J Cancer Res 78:1323–1328PubMedGoogle Scholar
  50. 50.
    Jee SH, Samet JM, Ohrr H et al (2004) Smoking and cancer risk in Korean men and women. Cancer Causes Control 15:341–348PubMedCrossRefGoogle Scholar
  51. 51.
    Ho SY, Lam TH, Jiang CQ et al (2002) Smoking, occupational exposure and mortality in workers in Guangzhou, China. Ann Epidemiol 12:370–377PubMedCrossRefGoogle Scholar
  52. 52.
    Sjodahl K, Lu Y, Nilsen TI et al (2007) Smoking and alcohol drinking in relation to risk of gastric cancer: a population-based, prospective cohort study. Int J Cancer 120:128–132PubMedCrossRefGoogle Scholar
  53. 53.
    Lindblad M, Rodriguez LA, Lagergren J (2005) Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case–control study. Cancer Causes Control 16:285–294PubMedCrossRefGoogle Scholar
  54. 54.
    Gonzalez CA, Pera G, Agudo A et al (2003) Smoking and the risk of gastric cancer in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer 107:629–634PubMedCrossRefGoogle Scholar
  55. 55.
    Siman JH, Forsgren A, Berglund G, Floren CH (2001) Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter pylori-infected individuals. Scand J Gastroenterol 36:208–213PubMedCrossRefGoogle Scholar
  56. 56.
    Nordlund L, Carstensen J, Pershagen G (1997) Cancer incidence in female smokers: a 26-year follow-up. Int J Cancer 73:625–628PubMedCrossRefGoogle Scholar
  57. 57.
    Engeland A, Andersen A, Haldorsen T, Tretli S (1996) Smoking habits and risk of cancers other than lung cancer: 28 years’ follow-up of 26,000 Norwegian men and women. Cancer Causes Control 7:497–506PubMedCrossRefGoogle Scholar
  58. 58.
    Tverdal A, Thelle D, Stensvold I et al (1993) Mortality in relation to smoking history: 13 years’ follow-up of 68,000 Norwegian men and women 35–49 years. J Clin Epidemiol 46:475–487PubMedCrossRefGoogle Scholar
  59. 59.
    Hansen S, Melby KK, Aase S et al (1999) Helicobacter pylori infection and risk of cardia cancer and non-cardia gastric cancer. A nested case–control study. Scand J Gastroenterol 34:353–360PubMedCrossRefGoogle Scholar
  60. 60.
    Jansson C, Johansson AL, Bergdahl IA et al (2005) Occupational exposures and risk of esophageal and gastric cardia cancers among male Swedish construction workers. Cancer Causes Control 16:755–764PubMedCrossRefGoogle Scholar
  61. 61.
    Freedman ND, Abnet CC, Leitzmann MF et al (2007) A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 165:1424–1433PubMedCrossRefGoogle Scholar
  62. 62.
    Chao A, Thun MJ, Henley SJ et al (2002) Cigarette smoking, use of other tobacco products and stomach cancer mortality in US adults: the Cancer Prevention Study II. Int J Cancer 101:380–389PubMedCrossRefGoogle Scholar
  63. 63.
    Galanis DJ, Kolonel LN, Lee J, Nomura A (1998) Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study. Int J Epidemiol 27:173–180PubMedCrossRefGoogle Scholar
  64. 64.
    Kneller RW, McLaughlin JK, Bjelke E et al (1991) A cohort study of stomach cancer in a high-risk American population. Cancer 68:672–678PubMedCrossRefGoogle Scholar
  65. 65.
    Padrão P, Lunet N, Santos AC, Barros H (2007) Smoking, alcohol, and dietary choices: evidence from the Portuguese National Health Survey. BMC Public Health 7:138PubMedCrossRefGoogle Scholar
  66. 66.
    Dallongeville J, Marécaux N, Fruchart JC, Amouyel P (1998) Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis. J Nutr 128:1450–1457PubMedGoogle Scholar
  67. 67.
    Peleteiro B, Bastos J, Barros H, Lunet N (2008) Systematic review of gastric intestinal metaplasia prevalence and its area level association with smoking. Gac Sanit (in press)Google Scholar
  68. 68.
    Peleteiro B, Lunet N, Figueiredo C et al (2007) Smoking, Helicobacter pylori virulence, and type of intestinal metaplasia in Portuguese males. Cancer Epidemiol Biomarkers Prev 16:322–326PubMedCrossRefGoogle Scholar
  69. 69.
    Mesquita P, Almeida R, Lunet N et al (2006) Metaplasia—a transdifferentiation process that facilitates cancer development. The model of gastric intestinal metaplasia. Crit Rev Oncog 12:3–26PubMedGoogle Scholar
  70. 70.
    Agudo A, Sala N, Pera G et al (2006) Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 15:2427–2434PubMedCrossRefGoogle Scholar
  71. 71.
    La Torre G, Boccia S, Ricciardi G (2005) Glutathione S-transferase M1 status and gastric cancer risk: a meta-analysis. Cancer Lett 217:53–60PubMedCrossRefGoogle Scholar
  72. 72.
    Sipponen P, Correa P (2002) Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern: etiologic hypothesis. Gastric Cancer 5:213–219PubMedCrossRefGoogle Scholar
  73. 73.
    Lopez A, Hollinshaw N, Piha T (1994) A descriptive model of the cigarette epidemic in developed countries. Tob Control 3:242–47Google Scholar
  74. 74.
    Santos AC, Barros H (2004) Smoking patterns in a community sample of Portuguese adults, 1999–2000. Prev Med 38:114–9PubMedCrossRefGoogle Scholar
  75. 75.
    Idris BI, Giskes K, Borrell C et al (2007) Higher smoking prevalence in urban compared to non-urban areas: time trends in six European countries. Health Place 13:702–712PubMedCrossRefGoogle Scholar
  76. 76.
    Huang XE, Tajima K, Hamajima N et al (2000) Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer. Nutr Cancer 38:30–36PubMedCrossRefGoogle Scholar
  77. 77.
    Palli D, Russo A, Saieva C et al (2000) Dietary and familial determinants of 10-year survival among patients with gastric carcinoma. Cancer 89:1205–1213PubMedCrossRefGoogle Scholar
  78. 78.
    Lunet N (2006) Gastric cancer frequency and trends. Arq Med 20:79–85Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Ricardo Ladeiras-Lopes
    • 1
  • Alexandre Kirchhofer Pereira
    • 1
  • Amanda Nogueira
    • 1
  • Tiago Pinheiro-Torres
    • 1
  • Isabel Pinto
    • 1
  • Ricardo Santos-Pereira
    • 1
  • Nuno Lunet
    • 1
    • 2
    Email author
  1. 1.Department of Hygiene and EpidemiologyPorto University Medical SchoolPortoPortugal
  2. 2.Serviço de Higiene e Epidemiologia, Faculdade de MedicinaUniversidade do PortoPortoPortugal

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