Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

Oncogene volume 25, pages 3756–3770 (2006)Cite this article

Abstract

Hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol consumption are major causes of hepatocellular carcinoma (HCC) worldwide. We performed a systematic review of epidemiologic studies carried out on HCC aetiology in Southern Europe, an area with an intermediate–high prevalence of these agents as well as of putative risk factors such as tobacco smoking, diabetes and obesity. To retrieve the articles, we performed a Medline search for titles and abstracts of articles. After the Medline search, we reviewed the papers and reference lists to identify additional articles. A synergism between HCV infection and HBV infection, overt (hepatitis B virus antigen (HbsAg) positivity) or occult (HBsAg negativity with presence of HBV DNA in liver or serum), is suggested by the results of some studies. The pattern of the risk for HCC due to alcohol intake shows a continuous dose–effect curve without a definite threshold, although most studies found that HCC risk increased only for alcohol consumption above 40–60 g of ethanol per day. Some evidence supports a positive interaction of alcohol intake probably with HCV infection and possibly with HBV infection. A few studies found that coffee has a protective effect on HCC risk due to various risk factors. Some data also support a role of tobacco smoking, diabetes and obesity as single agents or preferably co-factors in causing HCC. In countries with a relatively high alcohol consumption and intermediate levels of HCV and HBV infections (1–3% of population infected by each virus), such as Mediterranean countries, the three main risk factors together account for about 85% of the total HCC cases, leaving little space to other known risk factors, such as haemochromatosis, and to new, still unrecognised, factors as independent causes of HCC.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

Abbreviations

anti-HCV:

antibody to hepatitis C virus

BMI:

body mass index

HBsAg:

hepatitis B virus antigen

HBV:

hepatitis B virus

HCC:

hepatocellular carcinoma

HCV:

hepatitis C virus

HIV:

human immunodeficiency virus

IR:

incidence rate

NAFLD:

nonalcoholic fatty liver disease

NASH:

non alcoholic steatohepatitis

OR:

odds ratio

RR:

relative risk

References

  • Adami HO, Chow WH, Nyren O, Berne C, Linet MS, Ekbom A et al. (1996). J Natl Cancer Inst 88: 1472–1477.

  • Adami HO, Hsing AW, McLaughlin JK, Trichopoulos D, Hacker D, Ekbom A et al. (1992). Int J Cancer 51: 898–902.

  • Aizawa Y, Shibamoto Y, Takagi I, Zeniya M, Toda G . (2000). Cancer 89: 53–59.

  • Becker U, Gronbaek M, Johansen D, Sorensen TI . (2002). Hepatology 35: 868–875.

  • Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S . (2005). Hepatology 42: 44–52.

  • Bellentani S, Pozzato G, Saccoccio G, Crovatto M, Croce LS, Mazzoran L et al. (1999). Gut 44: 874–880.

  • Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M et al. (1997). Gut 41: 845–850.

  • Bellentani S, Tiribelli C . (2001). J Hepatol 35: 531–537.

  • Bellentani S, Tiribelli C, Saccoccio G, Sodde M, Fratti N, De Martin C et al. (1994). Hepatology 20: 1442–1449.

  • Benvegnù L, Fattovich G, Noventa F, Tremolada F, Chemello L, Cecchetto A et al. (1994). Cancer 74: 2442–2448.

  • Benvegnù L, Gios M, Boccato S, Alberti A . (2004). Gut 53: 744–749.

  • Bhattacharya R, Shuhart MC . (2003). J Clin Gastroenterol 36: 242–252.

  • Bosch FX, Ribes J, Diaz M, Cleries R . (2004). Gastroenterology 127: S5–S16.

  • Braga C, La Vecchia C, Negri E, Franceschi S . (1997). Eur J Cancer 33: 629–634.

  • Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P . (2001). Hepatology 34: 194–203.

  • Bugianesi E . (2005). Aliment Pharmacol Ther 22(Suppl 2): 40–43.

  • Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P et al. (2002). Gastroenterology 123: 134–140.

  • Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G . (1999). N Engl J Med 341: 22–26.

  • Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ . (2003). N Engl J Med 348: 1625–1638.

  • Casiglia E, Spolaore P, Ginocchio G, Ambrosio GB . (1993). Eur J Epidemiol 9: 293–297.

  • Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS et al. (2002). Am J Gastroenterol 97: 1211–1215.

  • Chen CJ, Liang KY, Chang AS, Chang YC, Lu SN, Liaw YF et al. (1991). Hepatology 13: 398–406.

  • Chen SY, Wang LY, Lunn RM, Tsai WY, Lee PH, Lee CS et al. (2002). Int J Cancer 99: 14–21.

  • Chen ZM, Liu BQ, Boreham J, Wu YP, Chen JS, Peto R . (2003). Int J Cancer 107: 106–112.

  • Chiaramonte M, Stroffolini T, Vian A, Stazi MA, Floreani A, Lorenzoni U et al. (1998). Cancer 85: 2132–2137.

  • Choudhury J, Sanyal AJ . (2004). Semin Liver Dis 24: 349–362.

  • Corrao G, Aricò S . (1998). Hepatology 27: 914–919.

  • Corrao G, Aricò S, Lepore R, Valenti M, Torchio P, Galatola G et al. (1993). J Clin Epidemiol 46: 601–607.

  • Corrao G, Aricò S, Zambon A, Torchio P, Lepore AR, Busellu G et al. (1997). J Hepatol 27: 470–476.

  • Corrao G, Bagnardi V, Zambon A, La Vecchia C . (2004). Prev Med 38: 613–619.

  • Corrao G, Bagnardi V, Zambon A, Torchio P . (1998a). Alcohol Alcohol 33: 381–392.

  • Corrao G, Torchio P, Zambon A, Ferrari P, Arico S, di Orio F . (1998b). Eur J Epidemiol 14: 447–456.

  • Corrao G, Zambon A, Bagnardi V, D'Amicis A, Klatsky A, Collaborative SIDECIR Group. (2001). Ann Epidemiol 11: 458–465.

  • Corrao G, Zambon A, Torchio P, Arico S, La Vecchia C, di Orio F . (1998c). J Hepatol 28: 608–614.

  • Cotrim HP, Parana R, Braga E, Lyra L . (2000). Am J Gastroenterol 95: 3018–3019.

  • Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ . (2004). Am J Epidemiol 159: 1160–1167.

  • Covolo L, Gelatti U, Talamini R, Garte S, Trevisi P, Franceschi S et al. (2005). Cancer Causes Control 16: 831–838.

  • Crespo J, Lozano JL, de la Cruz F, Rodrigo L, Rodriguez M, San Miguel G et al. (1994). Am J Gastroenterol 89: 1147–1151.

  • Cuadrado A, Orive A, Garcia-Suarez C, Dominguez A, Fernandez-Escalante JC, Crespo J et al. (2005). Obes Surg 15: 442–446.

  • Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB . (2005). Gut 54: 533–539.

  • del Olmo JA, Serra MA, Rodriguez F, Escudero A, Gilabert S, Rodrigo JM . (1998). J Cancer Res Clin Oncol 124: 560–564.

  • Doll R, Peto R, Hall E, Wheatley K, Gray R . (1994). BMJ 309: 901–911.

  • Donato F, Boffetta P, Puoti M . (1998). Int J Cancer 75: 347–354.

  • Donato F, Ribero ML, Menatti E, Gelatti U, Covolo L, Nardi G et al. (2005). Dig Liver Dis 37: A47 (abstract).

  • Donato F, Tagger A, Chiesa R, Ribero ML, Tomasoni V, Fasola M et al. (1997). Hepatology 26: 579–584.

  • Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A et al. (2002). Am J Epidemiol 155: 323–331.

  • El-Serag HB, Tran T, Everhart JE . (2004). Gastroenterology 126: 460–468.

  • Evans AA, Chen G, Ross EA, Shen FM, Lin WY, London WT . (2002). Cancer Epidemiol Biomarkers Prev 11: 369–376.

  • Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ . (2001). Semin Liver Dis 21: 17–26.

  • Fattovich G, Stroffolini T, Zagni I, Donato F . (2004). Gastroenterology 127: S35–S50.

  • Fong TL, Di Bisceglie AM, Waggoner JG, Banks SM, Hoofnagle JH . (1991). Hepatology 14: 64–67.

  • Gallus S, Bertuzzi M, Tavani A, Bosetti C, Negri E, La Vecchia C et al. (2002a). Br J Cancer 87: 956–959.

  • Gallus S, Tavani A, Negri E, La Vecchia C . (2002b). Ann Epidemiol 12: 202–205.

  • Gelatti U, Covolo L, Franceschini M, Pirali F, Tagger A, Ribero ML, et al. Brescia HCC Study Group. (2005a). J Hepatol 42: 528–534.

  • Gelatti U, Covolo L, Talamini R, Tagger A, Barbone F, Martelli C et al. (2005b). Int J Cancer 115: 301–306.

  • Goodman MT, Moriwaki H, Vaeth M, Akiba S, Hayabuchi H, Mabuchi K . (1995). Epidemiology 6: 36–41.

  • Hadziyannis S, Tabor E, Kaklamani E, Tzonou A, Stuver S, Tassopoulos N et al. (1995). Int J Cancer 60: 627–631.

  • Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB et al. (2001). Ann Intern Med 134: 120–124.

  • Haslam DW, James WP . (2005). Lancet 366: 1197–1209.

  • Hassan MM, Hwang LY, Hatten CJ, Swaim M, Li D, Abbruzzese JL et al. (2002). Hepatology 36: 1206–1213.

  • Heathcote EJ . (2004). Gastroenterology 127(5 Suppl 1): S294–S302.

  • Hezode C, Lonjon I, Roudot-Thoraval F, Mavier JP, Pawlotsky JM, Zafrani ES et al. (2003). Gut 52: 126–129.

  • Honjo S, Kono S, Coleman MP, Shinchi K, Sakurai Y, Todoroki I et al. (1999). Ann Epidemiol 9: 325–331.

  • Honjo S, Kono S, Coleman MP, Shinchi K, Sakurai Y, Todoroki I et al. (2001). J Clin Epidemiol 54: 823–829.

  • Hu KQ . (2002). J Viral Hepatitis 9: 243–257.

  • Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K et al. (2003). Hepatology 38: 420–427.

  • Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I et al. (1998). J Hepatol 28: 930–938.

  • Inoue M, Yoshimi I, Sobue T, Tsugane S, JPHC Study Group. (2005). J Natl Cancer Inst 97: 293–300.

  • International Agency for Research on Cancer (IARC) (1988). Alcohol Drinking IARC Monographs, vol. 44. International Agency for Research on Cancer: Lyon, France.

  • International Agency for Research on Cancer (IARC) (1991). Coffee, Tea, Mate, Methylxanthines and Methylglyoxal IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 51. International Agency for Research on Cancer: Lyon, France.

  • International Agency for Research on Cancer (IARC) (1994). Hepatitis Viruses IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 59. International Agency for Research on Cancer: Lyon, France.

  • Jee SH, Ohrr H, Sull JW, Samet JM . (2004). J Natl Cancer Inst 96: 1851–1856.

  • Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM . (2005). JAMA 293: 194–202.

  • Kamper-Jorgensen M, Gronbaek M, Tolstrup J, Becker U . (2004). J Hepatol 41: 25–30.

  • Klatsky AL, Armstrong MA . (1992). Am J Epidemiol 136: 1248–1257.

  • Klatsky AL, Armstrong MA, Friedman GD . (1993). Ann Epidemiol 3: 375–381.

  • Koike K, Yasuda K, Yotsuyanagi H, Moriya K, Hino K, Kurokawa K et al. (1995). J Med Virol 45: 236–239.

  • Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO et al. (2000a). Int J Cancer 85: 498–502.

  • Kuper H, Ye W, Broomè U, Romelsjo A, Mucci LA, Ekbom A et al. (2001). Hepatology 34: 714–718.

  • Kuper HE, Tzonou A, Kaklamani E, Hadziyannis S, Tasopoulos N, Lagiou P et al. (2000b). Cancer Causes Control 11: 171–175.

  • Kuriyama S, Tsubono Y, Hozawa A, Shimazu T, Suzuki Y, Koizumi Y et al. (2005). Int J Cancer 113: 148–157.

  • Kurozawa Y, Ogimoto I, Shibata A, Nose T, Yoshimura T, Suzuki H et al. JACC Study Group. (2005). Br J Cancer 93: 607–610.

  • La Vecchia C, Negri E, Decarli A, Franceschi S . (1997). Int J Cancer 73: 204–207.

  • Lagiou P, Kuper H, Stuver SO, Tzonou A, Trichopoulos D, Adami HO . (2000). J Natl Cancer Inst 92: 1096–1099.

  • Lecube A, Hernandez C, Genesca J, Esteban JI, Jardi R, Simo R . (2004). Diabetes Care 27: 1171–1175.

  • Liaw KM, Chen CJ . (1998). Tob Control 7: 141–148.

  • Liaw YF . (1995). Hepatology 22: 1101–1108.

  • Liu BQ, Peto R, Chen ZM, Boreham J, Wu YP, Li JY et al. (1998). BMJ 317: 1411–1422.

  • Loguercio C, Di Pierro M, Di Marino MP, Federico A, Disalvo D, Crafa E et al. (2000). Alcohol Alcohol 35: 296–301.

  • Mandayam S, Jamal MM, Morgan TR . (2004). Semin Liver Dis 24: 217–232.

  • Manno M, Camma C, Schepis F, Bassi F, Gelmini R, Giannini F et al. (2004). Gastroenterology 127: 756–763.

  • Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R et al. (2003). Hepatology 37: 917–923.

  • Marchesini G, Forlani G, Bugianesi E . (2005). Ann Med 37: 333–346.

  • Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS . (2002). Hepatology 36: 1349–1354.

  • Marrero JA, Lok AS . (2004). Gastroenterology 126: 347–350.

  • Mastrangelo G, Fedeli U, Fadda E, Valentini F, Agnesi R, Magarotto G et al. (2004). Environ Health Perspect 112: 1188–1192.

  • McGlynn KA, London WT . (2005). Best Pract Res Clin Gastroenterol 19: 3–23.

  • McKillop IH, Schrum LW . (2005). Alcohol 35: 195–203.

  • Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J et al. (2003). Hepatology 38: 50–56.

  • Mehta SH, Strathdee SA, Thomas DL . (2001). Epidemiol Rev 23: 302–312.

  • Mendenhall CL, Seeff L, Diehl AM, Ghosn SJ, French SW, Gartside PS et al. the VA Cooperative Study Group. (1991). Hepatology 14: 581–589.

  • Mizoue T, Tokui N, Nishisaka K, Nishisaka S, Ogimoto I, Ikeda M et al. (2000). Int J Epidemiol 29: 232–237.

  • Moller H, Mellemgaard A, Lindvig K, Olsen JH . (1994). Eur J Cancer 30A: 344–350.

  • Monto A, Patel K, Bostrom A, Pianko S, Pockros P, McHutchison JG et al. (2004). Hepatology 39: 826–834.

  • Morgan TR, Mandayam S, Jamal MM . (2004). Gastroenterology 127: S87–S96.

  • Mori M, Hara M, Wada I, Hara T, Yamamoto K, Honda M et al. (2000). Am J Epidemiol 151: 131–139.

  • Nair S, Mason A, Eason J, Loss G, Perrillo RP . (2002). Hepatology 36: 150–155.

  • Neuschwander-Tetri BA, Caldwell SH . (2003). Hepatology 37: 1202–1219.

  • N'Kontchou G, Paries J, Tin Tin Htar M, Ganne-Carrie N, Costentin L, Grando-Lemaire V et al. (2006). Clin Gastroenterol Hepatol (in press).

  • Pan SY, Johnson KC, Ugnat AM, Wen SW, Mao Y, Canadian Cancer Registries Epidemiology Research Group. (2004). Am J Epidemiol 159: 259–268.

  • Pessione F, Ramond MJ, Njapoum C, Duchatelle V, Degott C, Erlinger S et al. (2001). Hepatology 34: 121–125.

  • Peters MG, Terrault NA . (2002). Hepatology 36: S220–S225.

  • Pintus F, Mascia P . (1996). Eur J Epidemiol 12: 71–76.

  • Poikolainen K, Vartiainen E . (1997). Am J Epidemiol 146: 1019–1024.

  • Pollicino T, Squadrito G, Cerenzia G, Cacciola I, Raffa G, Crax A et al. (2004). Gastroenterology 126: 102–110.

  • Pontisso P, Ruvoletto MG, Fattovich G, Chemello L, Gallorini A, Ruol A et al. (1993). Gastroenterology 105: 1529–1533.

  • Poschl G, Seitz HK . (2004). Alcohol Alcohol 39: 155–165.

  • Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW . (1990). Hepatology 11: 74–80.

  • Poynard T, Bedossa P, Opolon P . (1997). Lancet 349: 825–832.

  • Raimondo G, Brunetto MR, Pontisso P, Smedile A, Maina AM, Saitta C et al. (2006). Hepatology 43: 100–107.

  • Rapp K, Schroeder J, Klenk J, Stoehr S, Ulmer H, Concin H et al. (2005). Br J Cancer 93: 1062–1067.

  • Ratziu V, Bonyhay L, Di Martino V, Charlotte F, Cavallaro L, Sayegh-Tainturier MH et al. (2002). Hepatology 35: 1485–1493.

  • Ratziu V, Heurtier A, Bonyhay L, Poynard T, Giral P . (2005). Aliment Pharmacol Ther 22(Suppl 2): 56–60.

  • Ratziu V, Poynard T . (2005). Hepatocellular carcinoma in NAFLD. In: Farrell G, De la Hall P, George J, McCullough AJ (eds). Fatty Liver Disease NASH and Related Disorders. Blackwell: Oxford (UK). pp 263–275.

    Google Scholar 

  • Regev A, Jeffers LJ . (1999). Alcohol Clin Exp Res 23: 1543–1551.

  • Regimbeau JM, Colombat M, Mognol P, Durand F, Abdalla E, Degott C et al. (2004). Liver Transpl 10: S69–S73.

  • Rockhill B, Newman B, Weinbarg C . (1998). Am J Public Health 88: 15–19.

  • Rothman KJ . (1986). Modern epidemiology. Little, Brown and Co.: Boston.

    Google Scholar 

  • Roudot-Thoraval F, Bastie A, Pawlotsky JM, Dhumeaux D, The Study Group for the Prevalence and the Epidemiology of Hepatitis C Virus. (1997). Hepatology 26: 485–490.

  • Ruhl CE, Everhart JE . (2005). Gastroenterology 129: 1928–1936.

  • Sagnelli E, Stroffolini T, Mele A, Almasio P, Coppola N, Ferrigno L et al. (2005). J Med Virol 75: 522–527.

  • Samanic C, Gridley G, Chow WH, Lubin J, Hoover RN, Fraumeni Jr JF . (2004). Cancer Causes Control 15: 35–43.

  • Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R et al. (2004). Gastroenterology 126: 1005–1014.

  • Sharp DS, Everhart JE, Benowitz NL . (1999). Ann Epidemiol 9: 391–393.

  • Shi J, Zhu L, Liu S, Xie WF . (2005). Br J Cancer 92: 607–612.

  • Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N et al. (2002). J Hepatol 37: 154–160.

  • Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S et al. (2004). Gastroenterology 126: 840–848.

  • Sorensen HT, Friis S, Olsen JH, Thurlstrup AM, Mellemkjaer L, Linet M et al. (1998). Hepatology 28: 921–925.

  • Sorensen HT, Mellemkjaer L, Jepsen P, Thulstrup AM, Baron J, Olsen JH et al. (2003). J Clin Gastroenterol 36: 356–359.

  • Squadrito G, Pollicino T, Cacciola I, Caccamo G, Villari D, La Masa T et al. (2006). Cancer 106: 1326–1330.

  • Staretz ME, Murphy SE, Patten CJ, Nunes MG, Koehl W, Amin S et al. (1997). Drug Metab Dispos 25: 154–162.

  • Stroffolini T, Chiaramonte M, Tiribelli C, Villa E, Simonetti RG, Rapicetta M et al. (1992). J Hepatol 16: 360–363.

  • Stroffolini T, Sagnelli E, Almasio P, Ferrigno L, Craxi A, Mele A, Italian Hospitals Collaborating Groups. (2004). Dig Liver Dis 36: 56–60.

  • Sun CA, Wu DM, Lin CC, Lu SN, You SL, Wang LY et al. (2003). Am J Epidemiol 157: 674–682.

  • Sun Z, Lu P, Gail MH, Pee D, Zhang Q, Ming L et al. (1999). Hepatology 30: 379–383.

  • Tanaka K, Tokunaga S, Kono S, Tokudome S, Akamatsu T, Moriyama T et al. (1998). Int J Epidemiol 27: 438–443.

  • Teli MR, Day CP, Burt AD, Bennett MK, James OF . (1995). Lancet 346: 987–990.

  • Torbenson M, Thomas DL . (2002). Lancet Infect Dis 2: 479–486.

  • Tverdal A, Skurtveit S . (2003). Ann Epidemiol 13: 419–423.

  • Tzonou A, Trichopoulos D, Kaklamani E, Zavitsanos X, Koumantaki Y, Hsieh CC . (1991). Int J Cancer 49: 377–380.

  • Vall Mayans M, Calvet X, Bruix J, Bruguera M, Costa J, Esteve J et al. (1990). Int J Cancer 46: 378–381.

  • Verlato G, Zoppini G, Bonora E, Muggeo M . (2003). Diabetes Care 26: 1047–1051.

  • Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT et al. (2004). J Natl Cancer Inst 96: 99–106.

  • Voigt MD . (2005). Clin Liver Dis 9: 151–169.

  • Wang LY, Chen CJ, Zhang YJ, Tsai WY, Lee PH, Feitelson MA et al. (1998). Am J Epidemiol 147: 315–323.

  • Wang LY, You SL, Lu SN, Ho HC, Wu MH, Sun CA et al. (2003). Cancer Causes Control 14: 241–250.

  • Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S et al. (1997). J Natl Cancer Inst 89: 1360–1365.

  • Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF et al. (2001). Cancer Causes Control 12: 13–21.

  • Wong RH, Chen PC, Wang JD, Du CL, Cheng TJ . (2003). J Occup Environ Med 45: 379–383.

  • Yamanaka T, Shiraki K, Nakazawa S, Okano H, Ito T, Deguchi M et al. (2001). Anticancer Res 21: 2937–2940.

  • Yotsuyanagi H, Hashidume K, Suzuki M, Maeyama S, Takayama T, Uchikoshi T . (2004). Alcohol Clin Exp Res 28: 181S–185S.

  • Yu MC, Tong MJ, Govindarajan S, Henderson BE . (1991). J Natl Cancer Inst 83: 1820–1826.

  • Yu MC, Yuan JM . (2004). Gastroenterology 127: S72–S78.

  • Yu MW, Hsu FC, Sheen IS, Chu CM, Lin DY, Chen CJ et al. (1997). Am J Epidemiol 145: 1039–1047.

  • Yuan JM, Govindarajan S, Arakawa K, Yu MC . (2004). Cancer 101: 1009–1017.

  • Zavitsanos X, Hatzakis A, Kaklamani E, Tzonou A, Toupadaki N, Broeksma C et al. (1992). Cancer Res 52: 5364–5367.

  • Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakanuma Y . (2001). Pathol Int 51: 127–131.

  • Zoli M, Magalotti D, Bianchi G, Gueli C, Marchesini G, Pisi E . (1996). Cancer 78: 977–985.

Download references

Acknowledgements

The following researchers kindly provided unpublished information regarding the characteristics and results of their studies: Professor M Colombo and Dr A Sangiovanni, IRCSS Maggiore Hospital and University of Milan, Milan; Dr L Benvegnù, University of Padova, Padova and Professor G Raimondo, University of Messina, Messina, Italy.

Author information

Authors and Affiliations

  1. Institute of Hygiene, Epidemiology and Public Health, University of Brescia, Brescia, Italy

    F Donato, U Gelatti & R M Limina

  2. Department of Gastroenterology, University of Verona, Verona, Italy

    G Fattovich

Authors
  1. F Donato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U Gelatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R M Limina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Fattovich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F Donato.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donato, F., Gelatti, U., Limina, R. et al. Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence. Oncogene 25, 3756–3770 (2006). https://doi.org/10.1038/sj.onc.1209557

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209557

Keywords

This article is cited by

Search

Advanced search

Quick links