A systematic review of meta-analyses on gene polymorphisms and gastric cancer risk

Current Genomics

Volumn 9, Issue 6, 2008, Pages 361-374

  Gianfagna, Francesco ^a   De Feo, Emma ^a   van Duijn, Cornelia M ^b   Ricciardi, Gualtiero ^a   Boccia, Stefania ^a  

^a CATHOLIC UNIVERSITY   (Italy)

^b ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Gastric cancer; Heterogeneity; Meta analysis; Polymorphism; Population attributable risk

Indexed keywords

EID: 54749097888     PISSN: 13892029     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920208785699544     Document Type: Review

References (86)

1. Verdecchia, A., Corazziari, I., Gatta, G., Lisi, D., Faivre, J., Forman, D.; EUROCARE Working Group. Explaining gastric cancer survival differences among European countries. Int. J. Cancer 2004, 109: 737-741.
2. Correa, P., Schneider, B.G. Etiology of gastric cancer: what is new? Cancer Epidemiol. Biomarkers Prev. 2005, 14: 1865-1868.
3. Zagari, R.M., Bazzoli, F. Gastric cancer: who is at risk? Dig. Dis. 2004, 22: 302-305.
4. Roberts-Thomson, I.C., Butler, W.J. Polymorphism and gastric cancer. J. Gastroenterol. Hepatol. 2005, 20: 793-794.
5. Hamilton, J.P., Meltzer, S.J. A review of the genomics of gastric cancer. Clin. Gastroenterol. Hepatol. 2006, 4: 416-425.
6. Boccia, S., Gianfagna, F., La Torre, G., Persiani, R., D'Ugo, D., van Duijn, C.M., Ricciardi, G. Genetic Susceptibility to Gastric Cancer: A review of the Published Meta-Analyses. In Cardinni, D.C. (ed.), Research Focus on Gastric Cancer. Hauppauge, NY: Nova Science Publishers 2008, 137-163.
7. Boccia, S., Brand, A., Brand, H., Ricciardi, G. The integration of gene-environment interactions into healthcare and disease prevention as a major challenge for Public Health Genomics. Mut. Res. in press.
8. Gonzalez, C.A., Sala, N., Capella, G. Genetic susceptibility and gastric cancer risk. Int. J. Cancer 2002, 100: 249-260.
9. Patsopoulos, N.A., Analatos, A.A., Ioannidis, J.P. Relative citation impact of various study designs in the health sciences. JAMA 2005, 293: 2362-2366.
10. Egger, M., Dickersin, K., Davey Smith, G. Problems and limitations in conducting systematic reviews. In Egger, M., Davey Smith, G., Altman, D.G. (eds.), Systematic reviews in health care. Meta-analysis in context. London, United Kingdom: BMJ Publishing Group, 2001, 43-68.
11. Oxman, A.D., Guyatt, G.H. Validation of an index of the quality of review articles. J. Clin. Epidemiol. 1991, 44: 1271-1278.
12. Deeks, J.J., Altman, D.G., Bradburn, M.J. Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In Egger, M., Davey Smith, G., Altman, D.G. (eds.), Systematic reviews in health care - meta-analysis in context. London, United Kingdom: BMJ Books 2005, 285-312.
13. Begg, C.B., Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994, 50: 1088-1101.
14. Egger, M., Smith, G.D., Schneider, M., Minder, C. Bias in meta-analysis detected by a simple graphical test. BMJ 1997, 315: 629-634.
15. Greenland, S., Rothman, K.J. Measures of effect and measures of association. In Rothman, K.J., Greenland, S. (eds.), Modern epidemiology, 2nd Edition. Philadelphia, PA: Lippincott-Raven 1998, 47-64.
16. Natarajan, S., Lipsitz, S.R., Rimm, E. A simple method of determining confidence intervals for population attributable risk from complex surveys. Stat. Med. 2007,26: 3229-3239.
17. Boccia, S., Hung, R., Ricciardi, G., Gianfagna, F., Ebert, M.P., Fang, J.Y., Gao, C.M., Götze, T., Graziaino, F., Lacasaña-Navarro, M, Lin, D., Löpez̀-Carrillo, L., Qiao, Y.L., Shen, H., Stolzenberg-Solomon, R., Takezaki, T., Weng, Y.R., Zhang, F.F., van Duijn, C.M., Boffetta, P., Taioli, E. Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk. a huge-GSEC review. Am. J. Epidemiol. 2008, 167: 505-516.
18. Wang, G.Y., Lu, C.Q., Zhang, R.M., Hu, X.H., Lou, Z.W. The E-cadeherin gene polymorphism 160C->A and cancer risk: A HuGE review and meta-analysis of 26 case-control studies. Am. J Epidemiol. 2009, 167: 7-14.
19. Lu, Y., Wang, Z.D., Shen, J., Xu, Y.C. Meta-analysis on the relationship between IL8-251 gene polymorphism, and gastric cancer. Zhonghua Yu Fang Yi Xue Za Zhi 2007, 41(Suppl.): 39-42.
20. Zhou, Y., Li, N., Zhuang, W., Liu, G.J., Wu, T.X., Yao, X., Du, L., Wei, M.L., Wu, X.T. P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature. Int. J. Cancer 2007, 121: 1481-1486.
21. Kamangar, F., Cheng, C., Abnet, C.C., Rabkin, C.S. Interleukin-1B polymorphisms and gastric cancer risk - a meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2006, 15: 1920-1928.
22. Camargo, M.C., Mera, R., Correa, P., Peek, R.M.Jr., Fontham, E.T., Goodman, K.J., Piazuelo, M.B., Sicinschi, L., Zabaleta, J., Schneider, B.G. Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis: Cancer Epidemiol. Biomarkers Prev. 2006, 15: 1674-1687.
23. Wang, P., Xia, H.H., Zhang, J.Y., Dai, L.P., Xu, X.Q., Wang, K.J. Association of interleukin-1 gene polymorphisms with gastric cancer a meta-analysis. Int. J Cancer 2007, 120: 552-562.
24. Zintzaras, E. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis. J. Hum. Genet. 2006, 51: 618-624.
25. Larsson, S.C., Giovannucci, E., Wolk, A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 2006, 131: 1271-1283.
26. Boccia, S., De Lauretis, A., Gianfagna, F., van Duijn, C.M., Ricciardi, G. CYP2E1 PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: A meta-analysis of the literature. Carcinogenesis 2007, 28: 101-106.
27. Saadat, M. Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis. Cancer Sci. 2006, 97: 505-509.
28. Boccia, S., La Torre, G., Gianfagna, F., Mannocci, A., Ricciardi, G. Glutathione S-transferase T1 status and gastric cancer risk: a meta-analysis of the literature. Mutagenesis 2006, 21: 115-123.
29. La Torre, G., Boccia, S., Ricciardi, G. Glutathione S-transferase M1 status and gastric cancer risk: a meta-analysis. Cancer Lett. 2005, 217: 53-60.
30. Macarthur, M., Hold, G.L., El-Omar, E.M. Inflammation and Cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am. J. Physiol. Gastrointest. Liver Physiol. 2004, 286: G515-G520.
31. Correa, P. Human gastric carcinogenesis: a multistep and multifactorial process - First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992, 52: 6735-6740.
32. Troost, E., Hold, G.L., Smith, M.G. Chow, W.H., Rabkin, C.S., McColl, K.E., El-Omar, E.M. The role of interleukin-1 beta and other potential genetic markers as indicators of gastric cancer risk. Can. J. Gastroenterol. 2003, 17(Suppl.B): 8B-12B.
33. Stark, G. Functional consequences of oxidative membrane damage. J. Membr. Biol. 2005, 205: 1-16.
34. Rozengurt, E., Walsh, J.H. Gastrin, CCK, signaling, and cancer. Annu. Rev. Physiol. 2001, 63: 49-76.
35. Takashima, M., Furuta, T., Hanai, H., Sugimura, H., Kaneko, E. Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils. Gut 2001, 48: 765-773.
36. Hwang, I.R, Kodama, T., Kikuchi, S., Sakai, K., Peterson, L.E., Graham, D.Y., Yamaoka, Y. Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection. Gastroenterology 2002, 123: 1793-1803.
37. Tu, S., Cui, G., Takaishi, S., Tran, A.V., Frederick, D.M., Carlson, J.E., Kurt-Jones, E., Wang, T.G. Overexpression of human interleukin-1beta in transgenic mice results in spontaneous gastric inflammation and carcinogenesis. Gastroenterology 2005, 128(Suppl.2): A62.
38. El-Omar, E.M., Carrington, M., Chow, W.H., McColl, K.E., Bream, J.H., Young, H.A., Herrera, J., Lissowska, J., Yuan, C.C., Rothman, N., Lanyon, G., Martin, M., Fraumeni, J.F.Jr., Rabkin, C.S. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000, 404(6776): 398-402.
39. Vamvakopoulos, J.E., Taylor, C.J., Morris-Stiff, G-J., Green, C., Metcalfe, S. The interleukin-1 receptor antagonist gene: a single-copy variant of the intron 2 variable number tandem repeat (VNTR) polymorphism. Eur. J. Immunogenet. 2002, 29: 337-340.
40. Pociot, F., Molvig, J., Wogense, L., Worsaae, H., Nerup, J.A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur. J. Clin. Invest. 1992, 22: 396-402.
41. Santtila, S., Savinainen, K., Hurme, M. Presence of the IL-IRA allele 2 (IL1RN* 2) is associated with enhanced IL-1beta production in vitro. Scand. J. Immunol. 1998, 47: 195-198.
42. Thakkinstian, A., McElduff, P., D'Este, C., Duffy, D., Attia, J. A method for metaanalysis of molecular association studies. Stat. Med. 2005, 24: 1291-1306.
43. Heinzmann, A., Ahlert, I., Kurz, T., Berner, R., Deichmann, K.A. Association study suggests opposite effects of polymorphisms within IL8 on bronchial asthma and respiratory syncytial virus bronchiolitis. J. Allergy Clin. Immunol. 2004, 114: 671-676.
44. Yoshino, N., Ishihara, S., Rumi, M,A., Ortega-Cava, C.F., Yuki, T., Kazumori, H., Takazawa, S., Okamoto, H., Kadowaki, Y., Kinoshita, Y. Interleukin-8 regulates expression of Reg protein in Helicobacter pylori-infected gastric mucosa. Am. J. Gastroenterol. 2005, 100: 2157-2166.
45. Brat, D.J., Bellail, A.C., Van Meir, E.G. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol. 2005, 7: 122-133.
46. Hull, J., Rowlands, K., Lockhart E., Sharland, M., Moore, C., Hanchard, N., Kwiatkowski, D.P. Haplotype mapping of the bronchiolitis susceptibility locus near IL8. Hum. Genet. 2004, 114: 272-279
47. Canedo, P., Castanheira-Vale, A.J., Lunet, N., Pereira, F., Figueiredo, C., Gioia-Patricola, L., Canzian, F., Moreira, H., Suriano, G., Barros, H., Carneiro, F., Seruca, R., Machado, J.C. The interleukin-8-251*T/*A polymorphism is not associated with risk for gastric carcinoma development in a Portuguese population. Eur. J. Cancer Prev. 2008, 17: 28-32.
48. Hull, J., Thomson, A., Kwiatkowski, D. Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax 2000, 55: 1023-1027.
49. Savage, S.A., Hou, L., Lissowska, J., Chow, W.H., Zatonski, W., Chanock, S.J., Yeager, M. Interleukin-8 polymorphisms are not associated with gastric cancer risk in a Polish population. Cancer Epidemiol. Biomarkers Prev. 2006, 15: 589-591.
50. Kamangar, F., Abnet, C.C., Hutchinson, A.A., Newschaffer, C.J., Helzlsouer, K., Shugart, Y.Y., Pietinen, P., Dawsey, S.M., Albanes, D., Virtamo, J., Taylor, P.R. Polymorphisms in inflammation-related genes and risk of gastric cancer (Finland). Cancer Causes Control 2006, 17: 117-125.
51. Savage, S.A., Abnet, C.C., Mark, S.D., Qiao, Y.L., Dong, Z.W., Dawsey, S.M., Taylor, P.R., Chanock, S.J. Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 2004, 13: 2251-2257.
52. Taguchi, A., Ohmiya, N., Shirai, K., Mabuchi, N., Itoh, A., Hirooka, Y., Niwa, Y., Goto, H. Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol. Biomarkers Prev. 2005, 14(11 Pt 1): 2487-2493.
53. Hayashi, S., Watanabe, J., Kawajiri, K. Genetic polymorphisms in the 5′-flanking region change transcriptional regulation of the human cytochrome P45011E1 gene. J. Biochem. 1991, 110: 559-565.
54. Guengerich, F.P., Kim, D.H., Iwasaki, M. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol. 1991, 4: 168-179.
55. Mueller, R.L., Bagel, H.J., Wild, H., Ruppin, H., Domschke, W. Nitrate and nitrite in normal gastric juice. Precursors of the endogenous N-nitroso compound synthesis. Oncology 1986, 43: 50-53.
56. Thorn, M., Finnstrom, N., Lundgren, S., Rane, A., Lööf, L. Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br. J. Clin. Pharmacol. 2005, 60: 54-60.
57. Danko, I.M., Chaschin, N.A. Association of CYP2E1 gene polymorphism with predisposition to cancer development. Exp. Oncol. 2005, 27: 248-256,
58. Garte, S., Gaspari, L., Alexandrie, A.K., Ambrosone, C., Autrup, H., Autrup, J.L., Baranova, H., Bathum, L., Benhamou, S., Boffetta, P., Bouchardy, C., Breskvar, K., Brockmoller, J., Cascorbi, I., Clapper, M.L., Coutelle, C., Daly, A., Dell'Omo, M., Dolzan, V., Dresler, C.M., Fryer, A., Raugen, A., Hein, D.W., Hildesheim, A., Hirvonen, A., Hsieh, L.L., Ingelman-Sundberg, M., Kalina, I., Kang, D., Kihara, M., Kiyohara, C., Kremers, P., Lazarus, P., Le Marchand, L., Lechner, M.C., van Lieshout, E.M., London, S., Manni, J.J,, Maugard, C.M., Morita, S., Nazar-Stewart, V., Noda, K., Oda, Y., Parl, F.F., Pastorelli, R., Persson, I., Peters, W.H., Rannug, A., Rebbeck, T., Risch, A., Roelandt, L., Romkes, M., Ryberg, D., Salagovic, J., Schoket, B., Seidegard, J., Shields, P.G., Sim, E., Sinnet, D., Strange, R.C., Stücker I., Sugimura, H., To-Figueras, J., Vineis, P., Yu, M.C., Taioli, E. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol. Biomarkers Prev. 2001, 10: 1239-1248.
59. Kato, S., Onda, M., Matsukura, N., Tokunaga, A., Tajiri, T., Kim, D.Y., Tsuruta, H., Matsuda, N., Yamashita, K., Shields, P.G. Cytochrome P4502E1 (CYP2E1) genetic polymorphism in a case-control study of gastric cancer and liver disease. Pharmacogenetics 1995, 5: S141-S144.
60. Egan, K.M., Cai, Q., Shu, X.O., Jin, F., Zhu, T.L., Dai, Q., Gao, Y.T., Zheng, W. Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2004, 13: 197-204.
61. Hayes, J.D., Pulford, D.J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 1995, 30: 445-600.
62. Strange, R.C., Spiteri, M.A., Ramachandran, S., Fryer, A.A. Glutathione Stransferase family of enzymes. Mutat. Res. 2001, 482: 21-26.
63. Saadat, I., Saadat, M. Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Lett. 2001, 169: 21-26.
64. Hashibe, M., Brennan, P., Strange, R.C., Bhisey, R., Cascorbi, I., Lazarus, P., Oude Ophuis, M.B., Benhamou, S., Foulkes, W.D., Katoh, T., Coutelle, C., Romkes, M., Gaspari, L., Taioli, E., Boffettá, P. Meta- and pooled-analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev. 2003, 12: 1509-1517.
65. Strange, R.C., Matharoo, B., Faulder, G.C., Jones, P., Cotton, W., Elder, J.B., Deakin, M. The human glutathione S-transferase: a case-control study of the incidence of the GST 10 phenotype in patients with adenocarcinoma. Carcinogenesis 1991, 12: 25-28.
66. Deakin, M., Elder, J., Hendrickse, C., Peckham, D., Baldwin, D., Pantin, C., Wild, N., Leopard, P., Bell, D.A., Jones, P., Duncan, H., Brannigan, K., Alldersea, J., Fryer, A.A., Strange, R.C. Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis 1996, 17: 881-884.
67. Bailey, L.B. Folate status assessment. J Nutr. 1990, 120(Suppl. 11): 1508-1511.
68. Bailey, L.B. Folate, methyl-related nutrients, alcohol, and the MTHFR 677C→-T polymorphism affect cancer risk: intake recommendations. J Nutr. 2003, 133(Suppl.1): 3748S-3753S.
69. Harrison, L.E., Zhang, Z.F., Karpeh, M.S., Sun, M., Kurtz, R.C. The role of dietary factors in the intestinal and diffuse histologic subtypes of gastric adenocarcinoma: a case-control study in the U.S. Cancer 1997, 80: 1021-1028.
70. Frosst, P., Blorn, H.J., Milos, R., Goyette, P., Sheppard, C.A., Matthews, R.G., Boers, G.J.H., den Heijer, M., Kluijtmans, L.A.J., van den Heuve, L.P., Rozen, R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetraltydrofolate reductase. Nat Genet. 1995, 10: 111-113.
71. Weisberg, I., Tran, P., Christensen, B., Sibani, S., Rozen, R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol. Genet. Metab. 1998, 64: 169-172.
72. Friedman, G., Goldschmidt, N., Friedlander, Y., Ben-Yehuda, A., Selbub, J., Babaey, S., Mendel, M., Kidron, M., Bar-On, H. A common mutation A1299C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. J. Nutr. 1999, 129: 1656-1661.
73. Choi, S.W., Mason, J.B. Folate and carcinogenesis: an integrated scheme, J. Nutr. 2000, 130: 129-132.
74. Shen, H., Xu, Y., Zheng, Y., Qian, Y., Yu, R., Qin, Y., Wang, X., Spitz, M.R., Wei, Q. Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study. Int. J. Cancer 2001, 95: 332-336.
75. Schabath, M.B., Wu, X., Wei, Q., Li, G., Gu, J., Spitz, M.R. Combined effects of the p53 and p73 polymorphisms on lung cancer risk. Cancer Epidemiol. Biomarkers Prev. 2006, 13: 158-1561.
76. Toyama, T., Zhang, Z., Nishio, M., Hamaguchi, M., Kondo, N., Iwase, H., Iwata, H., Takahashi, S., Yamashita, H., Fujii, Y. Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients. Breast Cancer Res. 2007, 9: R34.
77. Shepherd, T., Tolbert, D., Benedetti, J., Macdonald, J., Stemmermann, G., Wiest, J., DeVoe, G., Miller, M.A., Wang, J., Noffsinger, A., Fenoglio-Preiser, C. Alterations in exon 4 of the p53 gene in gastric carcinoma. Gastroenterology 2000, 118: 1039-1044.
78. Hiyama, T., Tanaka, S., Kitadai, Y., Ito, M., Sumii, M., Yoshihara, M., Shimamoto, F., Haruma, K., Chayama, K. p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis. Int. J. Cancer 2002, 100: 304-308.
79. Graziano, F., Humar, B., Guilford, P. The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Ann Oncol. 2003, 14: 1705-1713.
80. Pecina-Slaus, N. Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int. 2003, 3: 17.
81. Li, L.C., Chui, R.M., Sasaki, M., Nakajima, K., Perinchery, G., Au, H.C., Nojima, D., Carroll, P., Dahiya, R. A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res. 2000, 60: 873-876.
82. Wu, M.S., Huang, S.P., Chang, Y.T., Lin, M.T., Shun, C.T., Chang, M.C., Wang, H.P., Chen, C.J., Lin, J.T. Association of the - 160 C -> a promoter polymorphism of E-cadherin gene with gastric carcinoma risk. Cancer 2002, 94: 1443-1448.
83. Lau, J., Ioannidis, J.P.A., Schmid, C.H. Summing up evidence: one answer is not always enough. Lancet 1998, 351: 123-127.
84. Colhoun, H.M., McKeigue, P.M., Davey Smith, G. Problems of reporting genetic associations with complex outcomes. Lancet 2003, 361(9360): 865-872.
85. Boccia, S., La Torre, G., Persiani, R. D'Ugo, D., van Duijn, C.M., Ricciardi, G. A critical appraisal of epidemiological studies comes from basic knowledge: a reader's guide to assess potential for biases. World J Emerg. Surg. 2007, 2: 7.
86. Ricciardi, W., Boccia, S. Assessment of genomica as a priority for Public Health. Eurohealth 2007, 13: 7-9.