The Role of Serum Pepsinogen in the Detection of Gastric Cancer

The incidence of gastric cancer is very high in Japan, Korea, and China. Reducing the morbidity and mortality associated with gastric cancer requires early diagnosis, which can be facilitated by applying gastroscopy more frequently in high-risk groups. A strategy of population screening for gastric cancer is currently being adopted in Korea, Japan, and the Matsu region of Taiwan, but using different screening methods. In addition, the history of pepsinogen (PG) in research as a gastric cancer biomarker has varied, in that the use of serum levels of PGI and PGII and the PGI/PGII ratio as gastric cancer screening tools was introduced in Japan before 1990, but in Korea the first research results were only reported in 2008. This review first evaluates the physiology of PG, followed by the usefulness or limitations of serum PG testing with regard to the detection of gastric cancer. Finally, the factors affecting the efficacy of PG tests as a gastric cancer biomarker (i.e., Helicobacter pylori infection status, gender, histopathologic features, and cancer location and depth) are evaluated. It was found that the strategies used to increase the efficacy of PG tests should be individualized in each country according to the seroprevalence of H. pylori. (Gut Liver 2010;4:307-319)SHIN CM, 2010, J CLIN GASTROENTEROL, V44, pE34Shin CM, 2009, HELICOBACTER, V14, P512Kim HY, 2009, EUR J GASTROEN HEPAT, V21, P606, DOI 10.1097/MEG.0b013e3283086757Ren JS, 2009, GUT, V58, P636, DOI 10.1136/gut.2008.168641CHOI IJ, 2009, KOREAN J GASTROENTER, V54, P67IJIMA K, 2009, WORLD J GASTROENTERO, V15, P853Kim N, 2008, HELICOBACTER, V13, P245, DOI 10.1111/j.1523-5378.2008.00604.xLee JH, 2008, HELICOBACTER, V13, P288, DOI 10.1111/j.1523-5378.2008.00616.xKang JM, 2008, HELICOBACTER, V13, P146, DOI 10.1111/j.1523-5378.2008.00592.xHamashima C, 2008, JPN J CLIN ONCOL, V38, P259, DOI 10.1093/jjco/hyn017Yim JY, 2007, HELICOBACTER, V12, P333Hansen S, 2007, GUT, V56, P918, DOI 10.1136/gut.2006.114504Gotoda T, 2007, GASTRIC CANCER, V10, P1, DOI 10.1007/s10120-006-0408-1Mukoubayashi C, 2007, INTERNAL MED, V46, P261, DOI 10.2169/internalmedicine.46.6181TRAJKOV D, 2007, PRILOZI, V28, P39Kang HY, 2006, DIGEST DIS SCI, V51, P2310, DOI 10.1007/s10620-006-9276-0Yamada S, 2006, J GASTROENTEROL, V41, P1169, DOI 10.1007/s00535-006-1951-6Sasazuki S, 2006, CANCER EPIDEM BIOMAR, V15, P1341, DOI 10.1158/1055-9965.EPI-05-0901Fujishiro M, 2006, J EXP CLIN CANC RES, V25, P207Oishi Y, 2006, AM J EPIDEMIOL, V163, P629, DOI 10.1093/aje/kwj088MIKI K, 2006, GASTRIC CANCER, V9, P245NOMURA K, 2006, CANC STAT JAPAN 2005Liu CY, 2006, J MED SCREEN, V13, pS2Ang TL, 2005, J GASTROEN HEPATOL, V20, P1603, DOI 10.1111/j.1440-1746.2005.03898.xIijima K, 2005, J GASTROENTEROL, V40, P938, DOI 10.1007/s00535-005-1677-xWatabe H, 2005, GUT, V54, P764, DOI 10.1136/gut.2004.055400Hokkanen S, 2005, SCAND J CLIN LAB INV, V65, P291, DOI 10.1080/00365510510013848Parkin DM, 2005, CA-CANCER J CLIN, V55, P74Kokkola A, 2005, WORLD J GASTROENTERO, V11, P1032SHIN HR, 2005, CANC RES TREAT, V37, P325SEOANE A, 2005, GASTROENTEROL HEPATO, V28, P60NORMURA AM, 2005, J INFECT DIS, V191, P2075Ricci C, 2004, AM J GASTROENTEROL, V99, P1910, DOI 10.1111/j.1572-0241.2004.40614.xKikuchi S, 2004, LANGENBECK ARCH SURG, V389, P69, DOI 10.1007/s00423-004-0462-2Ohata H, 2004, INT J CANCER, V109, P138, DOI 10.1002/ijc.11680Onodera H, 2004, HEPATO-GASTROENTEROL, V51, P82CORREA P, 2004, GASTRIC CANCER, V7, P9Nardone G, 2003, ALIMENT PHARM THERAP, V17, P75Broutet N, 2003, BRIT J CANCER, V88, P1239, DOI 10.1038/sj.bjc.6600877Kiyohira K, 2003, J GASTROENTEROL, V38, P332Miki K, 2003, AM J GASTROENTEROL, V98, P735, DOI 10.1016/S0002-9270(03)00128-XSerafini M, 2002, GASTROENTEROLOGY, V123, P985, DOI 10.1053/gast.2002.35957Bodger K, 2001, HELICOBACTER, V6, P216Sandor J, 2001, EUR J EPIDEMIOL, V17, P443Yamagata H, 2000, ARCH INTERN MED, V160, P1962Kitahara F, 1999, GUT, V44, P693Gisbert JP, 1999, EUR J GASTROEN HEPAT, V11, P189Yoshihara M, 1998, AM J GASTROENTEROL, V93, P1090Hill MJ, 1998, EUR J CANCER PREV, V7, P173Terry P, 1998, INT J CANCER, V76, P35Kuipers EJ, 1998, ALIMENT PHARM THERAP, V12, P25KITAHARA F, 1998, GASTRIC CANCER, V1, P118DENDA K, 1998, NIPPON KOSHU EISEI Z, V45, P336Kinoshita Y, 1997, GUT, V41, P452Watanabe Y, 1997, DIGEST DIS SCI, V42, P1383Yasunaga Y, 1996, ITAL J GASTROENTEROL, V28, P457Aromaa A, 1996, AM J EPIDEMIOL, V144, P142FUCHS CS, 1995, NEW ENGL J MED, V333, P32KNIGHT T, 1995, EUR J GASTROEN HEPAT, V7, P647KIKUCHI S, 1995, INT J EPIDEMIOL, V24, P346CORREA P, 1995, AM J SURG PATHOL, V19, pS37WEBB PM, 1994, GASTROENTEROLOGY, V107, P1335WAGNER S, 1994, AM J GASTROENTEROL, V89, P1211PARSONNET J, 1993, CANCER EPIDEM BIOMAR, V2, P461YOUNG GO, 1992, ALIMENT PHARM THERAP, V6, P169ASAKA M, 1992, GASTROENTEROLOGY, V102, P760CAVE TR, 1991, SCAND J GASTROENTE S, V181, P9KIM JP, 1991, J GASTROENTEROL, V23, P428MIKI K, 1989, JPN J CANCER RES, V80, P111HUANG SC, 1988, JPN J CANCER RES, V79, P1139FELDMAN M, 1988, GASTROENTEROLOGY, V95, P630MIKI K, 1987, GASTROENTEROL JPN, V22, P133SIPPONEN P, 1985, INT J CANCER, V35, P173ICHINOSE M, 1982, CLIN CHIM ACTA, V126, P183SAMLOFF IM, 1982, GASTROENTEROLOGY, V83, P204SAMLOFF IM, 1982, GASTROENTEROLOGY, V82, P26KIMURA K, 1972, GASTROENTEROLOGY, V63, P584SAMLOFF IM, 1971, GASTROENTEROLOGY, V61, P185LAUREN P, 1965, ACTA PATHOL MIC SC, V64, P31