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International Journal of Clinical Oncology

, Volume 15, Issue 2, pp 126–134 | Cite as

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention

  • Masaru Morita
  • Ryuichi Kumashiro
  • Nobuhide Kubo
  • Yuichiro Nakashima
  • Rintaro Yoshida
  • Keiji Yoshinaga
  • Hiroshi Saeki
  • Yasunori Emi
  • Yoshihiro Kakeji
  • Yoshihisa Sakaguchi
  • Yasushi Toh
  • Yoshihiko Maehara
Review Article

Abstract

Both cigarette smoking and alcohol drinking are well-established risk factors for esophageal squamous cell carcinoma (ESCC), and the relationship of dose to cancer risk has already been described. Furthermore, the synergistic effect of these two factors has been reported. Our case–control study revealed the odds ratio of ESCC to be 50.1 for those who were both heavy smokers and heavy drinkers in comparison to people who neither drank nor smoked. In patients with ESCC, head and neck cancers as well as dysplastic lesions are frequently observed. Heavy smoking and heavy drinking are closely related to such multicentric carcinogenesis events in the upper aerodigestive tract (UADT), including the esophagus and head andneck region. Polymorphisms in acetaldehyde dehydrogenase 2 (ALDH2) are reported to be a key event in deciding individual susceptibility to UADT cancer. Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers. For the early detection of the disease, effective follow up using endoscopy with Lugol staining or narrow band imaging endoscopy is strongly recommended for high-risk populations, such as smokers, heavy drinkers, people with experience of flushing after the drinking of alcohol, and patients with UADT cancer.

Keywords

Esophageal cancer Smoking Drinking Multiple cancers Aldehyde dehydrogenase 

Notes

Acknowledgments

We thank Brian Quinn for his critical comments. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sport, Science and Technology of Japan.

Conflict of interest statement

No author has any conflict of interest.

References

  1. 1.
    World Health Organization. Data and Statistics. http://www.who.int/research/en/
  2. 2.
    Muller JM, Erasmi H, Stelzner M et al (1990) Surgical therapy of oesophageal carcinoma. Br J Surg 77:845–857CrossRefPubMedGoogle Scholar
  3. 3.
    Morita M, Yoshida R, Ikeda K et al (2008) Advances in esophageal cancer surgery in Japan: an analysis of 1000 consecutive patients treated at a single institute. Surgery 143:499–508CrossRefPubMedGoogle Scholar
  4. 4.
    International Agency for Research on Cancer (1986) Tobacco smoking. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol 38. IARC, LyonGoogle Scholar
  5. 5.
    International Agency for Research on Cancer (1988) Alcohol drinking. In: IARC monographs on the evaluation of carcinogenic risks to humans, vol 44. IARC, LyonGoogle Scholar
  6. 6.
    Boffetta P (2003) Oesophageal cancer. In: Stewart BW, Kleihues P (eds) World Cancer Report, World Health Organization, International Agency for Research on Cancer. IARC Press, Lyon, pp 223–227Google Scholar
  7. 7.
    Kinjo Y, Cui Y, Akiba S et al (1998) Mortality risks of oesophageal cancer associated with hot tea, alcohol, tobacco, and diet in Japan. J Epidemiol 8:235–243PubMedGoogle Scholar
  8. 8.
    Morita M, Saeki H, Mori M et al (2002) Risk factors for esophageal cancer and the multiple occurrence of carcinoma in the upper aerodigestive tract. Surgery 131:S1–S6CrossRefPubMedGoogle Scholar
  9. 9.
    Morita M, Kuwano H, Ohno S et al (1994) Multiple occurrence of carcinoma in the upper aerodigestive tract associated with esophageal cancer: reference to smoking, drinking and family history. Int J Cancer 58:207–210CrossRefPubMedGoogle Scholar
  10. 10.
    Morita M, Kuwano H, Nakashima T et al (1998) Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract. Int J Cancer 76:468–471CrossRefPubMedGoogle Scholar
  11. 11.
    Morita M, Araki K, Saeki H et al (2003) Risk factors for multicentric occurrence of carcinoma in the upper aerodigestive tract—analysis with a serial histologic evaluation of the whole resected-esophagus including carcinoma. J Surg Oncol 83:216–221CrossRefPubMedGoogle Scholar
  12. 12.
    Yokoyama A, Muramatsu T, Ohmori T et al (1998) Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis 19:1383–1387CrossRefPubMedGoogle Scholar
  13. 13.
    Yokoyama A, Kato H, Yokoyama T et al (2002) Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma. Carcinogenesis 23:1851–1859CrossRefPubMedGoogle Scholar
  14. 14.
    Yoshino I, Maehara Y (2007) Impact of smoking status on the biological behavior of lung cancer. Surg Today 37:725–734CrossRefPubMedGoogle Scholar
  15. 15.
    Sakata K, Hoshiyama Y, Morioka S et al (2005) Smoking, alcohol drinking and esophageal cancer: findings from the JACC study. J Epidemiol 15(Suppl II):S212–S219CrossRefPubMedGoogle Scholar
  16. 16.
    Fan Y, Yunan JM, Wang R et al (2008) Alcohol, tobacco, and diet in relation to esophageal cancer: the Shanghai cohort study. Nutr Cancer 60:354–363CrossRefPubMedGoogle Scholar
  17. 17.
    Takezaki T, Shinoda M, Hattoka S et al (2000) Subsite–specific risk factors for hypopharyngeal and esophageal cancer (Japan). Cancer Causes Control 11:597–608CrossRefPubMedGoogle Scholar
  18. 18.
    Tavani A, Negri E, Franceschi S et al (1993) Risk factors for esophageal cancer in women in Northern Italy. Cancer 72:2531–2536CrossRefPubMedGoogle Scholar
  19. 19.
    Castellsague X, Munoz N, DeStefani E et al (1999) Independent and joint effects of tobacco smoking and alcohol drinking on the risk of esophageal cancer in men and women. Int J Cancer 82:657–664CrossRefPubMedGoogle Scholar
  20. 20.
    Gallus S, Bosetti C, Franceschi S et al (2001) Oesophageal cancer in women: tobacco, alcohol, nutrition and hormonal factors. Br J Cancer 85:341–345CrossRefPubMedGoogle Scholar
  21. 21.
    Pandeya N, Williams G, Green AC et al (2009) Alcohol consumption and risks of adenocarcinoma and squamous cell carcinoma of the esophagus. Gastroenterology 136:1215–1224CrossRefPubMedGoogle Scholar
  22. 22.
    Launoy G, Milan CH, Faivre J et al (1997) Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption, mean intake, current and former consumption. Br J Cancer 75:1389–1396Google Scholar
  23. 23.
    Lee CH, Wu DC, Lee JM et al (2007) Carcinogenetic impact of alcohol intake on squamous cell carcinoma risk of oesophagus in relation to tobacco smoking. Eur J Cancer 43:1188–1199CrossRefPubMedGoogle Scholar
  24. 24.
    Seitz HK, Stickel F (2007) Molecular mechanisms of alcohol mediated carcinogenesis. Nat Rev Cancer 7:599–612CrossRefPubMedGoogle Scholar
  25. 25.
    Salaspuro V, Salaspuro M (2004) Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva. Int J Cancer 111:480–483CrossRefPubMedGoogle Scholar
  26. 26.
    Homann N, Tillonen J, Meurman JH et al (2000) Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer. Carcinogenesis 21:663–668CrossRefPubMedGoogle Scholar
  27. 27.
    Homann N, Tillonen J, Rintamaki H et al (2001) Poor dental status increases acetaldehyde production from ethanol in saliva: a possible link to increased oral cancer risk among heavy drinkers. Oral Oncol 37:153–158CrossRefPubMedGoogle Scholar
  28. 28.
    Kuratsune M, Kochi S, Horie A (1965) Carcinogenesis in the esophagus. I. Penetration of benzo[a]pyrene and other hydrocarbon into the esophageal mucosa. Gann 56:177–187PubMedGoogle Scholar
  29. 29.
    Gao YT, Mc Laughlin JK, Blot WJ et al (1994) Risk factors for esophageal cancer in Shanghai, China. I. Role of cigarette smoking and alcohol drinking. Int J Cancer 58:192–196CrossRefPubMedGoogle Scholar
  30. 30.
    Slaughter DP, Southwick HW, Smejkal W (1953) “Field cancerization” in oral stratified epithelium. Cancer 6:963–968CrossRefPubMedGoogle Scholar
  31. 31.
    Morita M, Kuwano H, Yasuda M et al (1994) The multicentric occurrence of squamous epithelial dysplasia and squamous cell carcinoma in the esophagus. Cancer 74:2889–2895CrossRefPubMedGoogle Scholar
  32. 32.
    Kuwano H, Matsuda H, Matsuoka H et al (1987) Intra-epithelial carcinoma concomitant with esophageal squamous cell carcinoma. Cancer 59:783–787CrossRefPubMedGoogle Scholar
  33. 33.
    Kuwano H, Ohno S, Matsuda H et al (1988) Serial histologic evaluation of multiple primary squamous cell carcinoma of the esophagus. Cancer 61:1635–1638CrossRefPubMedGoogle Scholar
  34. 34.
    Tsutsui S, Kuwano H, Mori M et al (1991) Comparison of cell nuclear DNA contents between intraepithelial and invasive components of oesophageal squamous cell carcinoma. Eur J Cancer 27:620–624CrossRefPubMedGoogle Scholar
  35. 35.
    Kuwano H, Morita M, Tsutsui S et al (1991) Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer. J Surg Oncol 46:107–109CrossRefPubMedGoogle Scholar
  36. 36.
    Miyazaki M, Ohono S, Futatsugi M et al (2002) The relation of alcohol consumption and cigarette smoking to the multiple occurrence of esophageal dysplasia and squamous cell carcinoma. Surgery 131:S7–S13CrossRefPubMedGoogle Scholar
  37. 37.
    Matsubara T, Yamada K, Nakagawa A (2003) Risk of second primary malignancy after esophagectomy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol 21:4336–4341CrossRefPubMedGoogle Scholar
  38. 38.
    Morita M, Kuwano H, Baba H et al (1998) Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma. Cancer 83:1307–1311CrossRefPubMedGoogle Scholar
  39. 39.
    Hollstein M, Hergenhahn M, Yang Q et al (1999) New approaches to understanding p53 gene tumor mutation spectra. Mutat Res 431:199–209PubMedGoogle Scholar
  40. 40.
    Saeki H, Ohno S, Araki K et al (2000) Alcohol consumption and cigarette smoking in relation to high frequency of p53 protein accumulation in oesophageal squamous cell carcinoma in the Japanese. Br J Cancer 82:1892–1894CrossRefPubMedGoogle Scholar
  41. 41.
    Saeki H, Ohno S, Miyazaki M et al (2002) p53 protein accumulation in multiple oesophageal squamous cell carcinoma: relationship to risk factors. Oncology 62:175–179CrossRefPubMedGoogle Scholar
  42. 42.
    Egashira A, Morita M, Kakeji Y et al (2007) p53 gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: results in Japan and comparison with other countries. Cancer Sci 98:1152–1156CrossRefPubMedGoogle Scholar
  43. 43.
    Oki E, Zhao Y, Yoshida R et al (2009) The difference in p53 mutations between cancers of the upper and lower gastrointestinal tract. Digestion 79(Suppl 1):33–39CrossRefPubMedGoogle Scholar
  44. 44.
    Ito S, Ohga T, Saeki H et al (2005) p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate carcinogenesis. Int J Cancer 113:22–28CrossRefPubMedGoogle Scholar
  45. 45.
    Mori M, Mimori K, Shiraishi T et al (2000) Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus. Cancer Res 60:1177–1182PubMedGoogle Scholar
  46. 46.
    Morita M, Oyama T, Nakata S et al (2006) Expression of FHIT in esophageal epithelium and carcinoma: reference to drinking, smoking and multicentric carcinogenesis. Anticancer Res 26:2243–2248PubMedGoogle Scholar
  47. 47.
    Soma T, Kagonoi J, Kawabe A et al (2006) Nicotine induces the fragile histidine triad methylation in human esophageal squamous cells. Int J Cancer 119:1023–1027CrossRefPubMedGoogle Scholar
  48. 48.
    Brooks PJ, Theruvathu JA (2005) DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol 35:187–193CrossRefPubMedGoogle Scholar
  49. 49.
    Paget V, Lechevrel M, Sichel F (2008) Acetaldehyde-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the FASAY (functional analysis of separated alleles in yeast). Mutat Res 652:12–19PubMedGoogle Scholar
  50. 50.
    Higuchi S, Matsushita S, Murayama M et al (1995) Alcohol and aldehyde dehydrogenase polymorphism and the risk for alcoholism. Am J Psychiatry 152:1219–1221PubMedGoogle Scholar
  51. 51.
    Mizoi Y, Yamamoto K, Ueno Y et al (1994) Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenases in individual variation of alcohol metabolism. Alcohol Alcohol 29:707–710Google Scholar
  52. 52.
    Takeshita T, Morimoto K (1998) Development of a questionnaire method to discriminate between typical and atypical genotypes of low Km aldehyde dehydrogenase in a Japanese population. Alcohol Clin Exp Res 22:1409–1413Google Scholar
  53. 53.
    Yokoyama A, Ohmori T, Muramatsu T et al (1996) Cancer screening of upper aerodigestive tract in Japanese alcoholics with reference to drinking and smoking habits and aldehyde dehydrogenase-2 genotype. Int J Cancer 68:313–316CrossRefPubMedGoogle Scholar
  54. 54.
    Yokoyama A, Muramatsu T, Ohmori T et al (2001) Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics. Carcinogenesis 22:433–439CrossRefPubMedGoogle Scholar
  55. 55.
    Yokoyama A, Ohmori T, Muramatsu T et al (1996) Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics. Cancer 77:1986–1990CrossRefPubMedGoogle Scholar
  56. 56.
    Muto M, Hitomi Y, Ohtsu A (2000) Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients. Gut 47:256–261CrossRefPubMedGoogle Scholar
  57. 57.
    Muto M, Takahashi M, Ohtsu A et al (2005) Risk of multiple squamous cell carcinoma in the esophagus and the head and neck region. Carcinogenesis 26:1008–1012CrossRefPubMedGoogle Scholar
  58. 58.
    Yokoyama A, Tsutsumi E, Imazeki H et al (2008) Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype. Alcohol Clin Exp Res 32:1607–1614CrossRefPubMedGoogle Scholar
  59. 59.
    Morita M, Oyama T, Kagawa N et al (2005) Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer. Front Biosci 10:2319–2324CrossRefPubMedGoogle Scholar
  60. 60.
    Oyama T, Isse T, Kagawa N et al (2005) Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism. Front Biosci 10:951–960CrossRefPubMedGoogle Scholar
  61. 61.
    Oyama T, Isse T, Ogawa M et al (2007) Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice. Front Biosci 12:1927–1934CrossRefPubMedGoogle Scholar
  62. 62.
    World Cancer Research Fund in Association with American Institute for Cancer Research (1997) Oesophagus. In: Food, nutrition and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington DC, pp 118–129Google Scholar
  63. 63.
    La Vechia C, Altieri A, Tavani A (2001) Vegetables, fruit, antioxidants and cancer: a review of Italian studies. Eur J Nutr 40:261–267CrossRefGoogle Scholar
  64. 64.
    Yamaji T, Inoue M, Sasazuki S et al (2008) Fruits and vegetable and squamous cell carcinoma of the esophagus in Japan: the JPHC study. Int J Cancer 123:1935–1940CrossRefPubMedGoogle Scholar
  65. 65.
    Kreimer AR, Randi G, Herrero R et al (2006) Diet and body mass, and oral and oropharyngeal squamous cell carcinomas: analysis from IARC multinational case–control study. Int J Cancer 118:2293–2297CrossRefPubMedGoogle Scholar
  66. 66.
    Galeone C, Pelucchi C, Levi F et al (2006) Folate intake and squamous-cell carcinoma of the oesophagus in Italian and Swiss men. Ann Oncol 17:521–525CrossRefPubMedGoogle Scholar
  67. 67.
    Yokoyama T, Saito K, Lwin H et al (2005) Epidemiological evidence that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated mean corpuscular volume in alcohol drinkers. Alcohol Clin Exp Res 29:622–630CrossRefPubMedGoogle Scholar
  68. 68.
    Toh Y, Sakaguchi Y, Ikeda O et al (2009) The triangulating stapling technique for cervical esophago anastomosis after esophagectomy. Surg Today 39:201–206CrossRefPubMedGoogle Scholar
  69. 69.
    National Cancer Center (2009) Trends in consumption of tobacco, alcohol and food, Cancer Statistics in Japan ‘09. http://ganjoho.ncc.go.jp/public/statistics/backnumber/2009_en.html
  70. 70.
    Yokoyama T, Yokoyama A, Kato H et al (2003) Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes and risk for esophageal squamous cell carcinoma in Japanese men. Cancer Epidemiol Biomarkers Prev 12:1227–1233Google Scholar
  71. 71.
    Katada C, Muto M, Momma K et al (2007) Clinical outcome after endoscopic mucosal resection for esophageal squamous cell carcinoma invading the muscularis mucosae–a multicenter retrospective cohort study. Endoscopy 39:779–783CrossRefPubMedGoogle Scholar
  72. 72.
    Sugimachi K, Ohno S, Matsuda H et al (1987) Lugol-combined endoscopic detection of minute lesions of the thoracic esophagus. Ann Surg 208:179–183CrossRefGoogle Scholar
  73. 73.
    Larghi A, Lecca PG, Costamagna G (2008) High-resolution narrow band imaging endoscopy. Gut 57:976–986CrossRefPubMedGoogle Scholar
  74. 74.
    Takenaka R, Kawahara Y, Okada H et al (2009) Narrow-band imaging provides reliable screening for esophageal malignancy in patients with head and neck cancers. Am J Gastroenterol 104:2942–2948CrossRefPubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2010

Authors and Affiliations

  • Masaru Morita
    • 1
  • Ryuichi Kumashiro
    • 1
  • Nobuhide Kubo
    • 1
  • Yuichiro Nakashima
    • 1
  • Rintaro Yoshida
    • 1
  • Keiji Yoshinaga
    • 1
  • Hiroshi Saeki
    • 1
  • Yasunori Emi
    • 1
  • Yoshihiro Kakeji
    • 1
  • Yoshihisa Sakaguchi
    • 2
  • Yasushi Toh
    • 1
    • 2
  • Yoshihiko Maehara
    • 1
  1. 1.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Gastroenterological SurgeryNational Kyushu Cancer CenterFukuokaJapan

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