Original Article
Gastric cancer: A case study in Turkey ABSTRACT Objective: The aim of this study was to determine age-specific incidence ratios, gastric cancer localization trend, histologic subtype and cancer related survival that whether have changed during the period from 1999 to 2010. Materials and Methods: A total of 866 gastric cancer patients treated at the hospital were retrospectively evaluated. Categorical and continuous variables were summarized using descriptive statistics and were compared using the Chi-square and Mann-Whitney U-tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: The median age at diagnosis was 58 years. Trends concerning the median ages of the patients were increased (from 57 years to 59 years). The proportion of diffuse histological subtype gastric adenocarcinoma increased during the period from 1999 to 2010, and it was 27% between 1999 and 2002 and 32% between 2007 and 2010 (P = 0.04). The proportion of gastric adenocarcinoma localized in cardia increased during the period from 1999 to 2010, and was 7.2% between 1999 and 2002; and 22.5% in 2007 and 2010 (P = 0.004). For stage I that was diagnosed between 1999 and 2002, the relative survival was 67% and in patients diagnosed between 2007 and 2010 the rate was 85%. For stage II that was diagnosed between 1999 and 2002, the relative survival was 35% and in patients diagnosed between 2007 and 2010, the rate was 65%. Cox regression analysis was conducted based on age subgroup, diagnosis time, and gastric localization (proximal/distal) and for adenocarcinoma subtypes. Hazard ratio was 31.6 for stage IV (confidence interval [CI] = 10-42), 1.3 for cardia localization (CI = 1.04-1.6) and 1.37 for patients who had been diagnosed between 1999 and 2002 (1.14-1.78). Conclusions: The ratio of median age at diagnosis and proximal gastric adenocarcinoma, diffuse histologic subtype increased between 1999 and 2010. Cancer related survival significantly improved for stage I and stage II. Cardia localization and time of diagnosis between 1999 and 2002 had significantly poor outcome on relative survival. KEY WORDS: Gastric cancer, intestinal and diffuse subtype, proximal/distal ratio, stages and survival
INTRODUCTION Incidence and mortality rates for most cancers are decreasing in the United States (US) and other more developed western countries.[1,2] Although much progress has been made in reducing mortality rates, stabilizing incidence rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85.[3] Increases are expected in the future because of long life expectancy. Cancer has increasingly become a common problem for older people due to the prolonged life expectancy of the general population.
Gastric cancers have also increased with age, especially in elderly people.[9] Gastric cancer in older persons has increasingly become a common problem in the last years. Data of 866 patients were collected from hospital based registries from 1999 to 2010. The aim of this study was to determine age specific incidence ratios, gastric cancer localization trend (proximal/ distal), gastric cancer histologic subtype at the stage of diagnosis and cancer relative survival that have changed during the period from 1999 to 2010.
Deniz Tural1, Fatih Selçukbiricik2, Emre Akar2, Süheyla Serdengeçti3, Evin Büyükünal2 Department of Internal Medicine, Division of Medical Oncology, Akdeniz University, School of Medicine, Antalya, Turkey, 2Departments of Internal Medicine, Division of Medical Oncology, Istanbul University, Cerrahpaşa Medical Faculty, Istanbul, Turkey, 3 Medical Student, Istanbul University, Cerrahpaşa Medical Faculty, Istanbul, Turkey 1
For correspondence: Dr. Emre Akar, Istanbul University, Cerrahpasa Medical Faculty, TR-34098 Istanbul, Turkey. E-mail: emrevonakar@ gmail.com
Overall gastric cancer incidence and mortality are decreasing world-wide. However, despite its recent decline, gastric cancer is the fourth most common cancer and the second leading cause of cancerrelated deaths world-wide.[4-6] In contrast to the decreasing overall gastric cancer incidence rates (distal stomach), incidence rates have increased for cancer of cardia (proximal part of the stomach) in the US and many European countries, including Denmark and United Kingdom.[7,8]
Gastric cancer patients treated in our hospital between 1999 and 2010 were retrospectively evaluated. Cancer was coded according to the International Classification of Disease for Oncology, 3rd edition.[10] We included only gastric adenocarcinoma in this study. Patients were included when adenocarcinoma of the stomach was histologically confirmed and survival data were
644
Journal of Cancer Research and Therapeutics - October-December 2013 - Volume 9 - Issue 4
MATERIALS AND METHODS Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.126466 PMID: 24518710 Quick Response Code:
Tural, et al.: Patterns of gastric cancer in Turkey altered
available. Patients were excluded when a tumor other than adenocarcinoma was histologically identified. We divided cases into two subgroups based on anatomic localization in the stomach; as Group 1: Proximal stomach (cardia) and Group 2: Noncardia (gastric antrum, pylorus, lesser curvature and greater curvature of the stomach).[8] After we determined the ages of each cancer patient, number of cancer cases were categorized into two age groups; those 70 years old or younger than 70 years of age and older than 70 years. The cases were divided into three groups based on histopathological subtype: Group 1; intestinal gastric cancer and Group 2; diffuse gastric cancer and Group 3; mixed adenocarcinoma.[11] Gastric adenocarcinoma stage was determined according to the seventh edition of the International Union Against Cancer guidelines. Statistical analysis Categorical and continuous variables were summarized using the descriptive statistics (e.g., median, range, frequency, and percentage) and compared with Chi-square and Mann-Whitney U-tests, respectively. The median age rates between 1999 and 2010 for five age groups were calculated for 1 year period and 4 years periods. Proximal/distal gastric ratios, intestinal/diffuse adenocarcinoma ratios, at-diagnosis stage and cancer specific survival were calculated for 4 years periods. Cancer specific survival rates were estimated by the KaplanMeier method and cancer relative survival was calculated from the date of diagnosis until death from gastric adenocarcinoma. We evaluated the effect of five age groups, tumor localization (proximal/distal), diagnosis time, histologic subtype and stage on relative survival by Cox regression analyzes. All analyzes were performed using the SPSS 15.0 (SPSS Inc., Chicago, IL, USA) software. The statistical level of significance was defined as P < 0.05.
Table 1: The demographic data of 866 patients with gastric cancer Variable Gender Male Female Median age (range) Time to diagnosis age >70 year 70 yearde Histology Diffuse adenocarcinoma Intestinal adenocarcinoma Mixed adenocarcinoma Stomach localization Cardia part Distal part Time to diagnosis stage Stage I Stage II Stage III Stage IV
N (%) 606 (70) 260 (30) 58 (22-90) 151 (17) 715 (83) 265 (30) 536 (62) 65 (8) 158 (18) 708 (82) 80 (9) 150 (16) 212 (25) 424 (50)
Figure 1: The changes of the annual values rates of patients older than 70 years are shown in 1-year periods between 1999 and 2010
RESULTS Details of tumor characteristic are shown Table 1 between 1999 and 2010, there were 866 cases of gastric adenocarcinoma recorded in hospital based registries. The median age at diagnosis was 58 years (range = 22-90). When compared to Surveillance, Epidemiology and End Results (SEER) data consisting of the time period from 1999 to 2003, median age of our cohort was found to be younger than American patients.[9] The median age was 57 years during 1999-2002 period, 58 years between 2003 and 2006 and 59 years between 2007 and 2010. Gastric adenocarcinoma in patients older than 70 years increased between 1999 and 2010. Between 1999 and 2002, the ratio of patients who were older than 70 years was 9.8%. This ratio increased and between 2007 and 2010, 20% were older than 70 years (P = 0.001). The changes of the rates of annual values for patients older than 70 years are shown in Figure 1.
Figure 2: The proportion of cardia (proximal stomach) adenocarcinoma increased between 1999 and 2010
The proportion of gastric adenocarcinoma localized in cardia, increased during the period from 1999 to 2010, and was 7.2% between 1999 and 2002; and 22.5% in 2007-2010 (P = 0.004). The details of proximal/distal stomach ratio are shown in Figure 2. Stage III and stage IV constituted the dominant proportion in the time of diagnosis, but stage I and II gastric adenocarcinoma
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increased from 15% to 25% between 1999 and 2010. The details of stage changed during 1999-2010 are demonstrated in Figure 3. The proportion of diffuse histological subtype gastric adenocarcinoma increased during the period from 1999 to 2010, and it was 27% between 1999 and 2002 and 32% between 2007 and 2010. The ratio of intestinal adenocarcinoma also decreased (from 65% to 59%) and this difference was statistically significant (P = 0.04) [Figure 4].
and 2002, the relative survival was 4% (95% CI = 3-5%) and this ratio remained the same (95% CI = 3.5-5%) for patients who were diagnosed between 2007 and 2010. The details of the relative survival ratio changes are shown in Figure 5. Cox regression analysis was conducted, based on age subgroup, diagnosis time, and gastric localization (proximal/distal), and for adenocarcinoma subtypes. Hazard ratio was 31.6 for stage IV (CI = 10-42), 1.3 for cardia localization (CI = 1.04-1.6) and 1.37 for patients who had been diagnosed between 1999 and 2002 (1.14-1.78). Details of Cox regression analysis are shown in the Table 2.
For stage I diagnosed between the years 1999 and 2002, the relative survival was 67% (95% confidence interval [CI] = 63-71%) and 85% (95% CI = 80-90%) for patients who were diagnosed during 2007-2010 and for stage II diagnosed between 1999 and 2002, the relative survival was 35% (95% CI = 31-39%) and that diagnosed between 2007 and 2010 was 65% (95% CI = 61-69%). Relative survival improved both for stages I and II during 1999-2010. For stage III diagnosed between 1999 and 2002, the relative survival was 15% (95% CI = 13-17%) and that diagnosed between 2007 and 2010 was 21% (95% CI = 17-25%) and this ratio was statistically not significant (P = 0.12). For stage IV diagnosed between 1999
Gastric cancer is the fourth most commonly diagnosed cancer. [12] However, incidence rates for gastric cancer have decreased worldwide.[4-6,13,14] Currently, gastric cancer is the second leading cause of cancer related death in both men and women. [12-15] Gastric cancers also have increased with age, especially in elderly[9] gastric cancer in older people has increasingly become a common problem in the recent years. In the current study, median age increased from 57 to 59 during the period from
Figure 3: Changed proportion of stage between 1999–2010.
Figure 4: Diffuse adenocarcinoma/intestinal adenocarcinoma ratio
DISCUSSION
Table 2: Results of cox regression analysis for the association between relative survival and diagnosis time, age groups, tumor localization and tumor histological subtype, between 1999 and 2010 Variable
Figure 5: Between 1999 and 2010, change in the relative survival ratio for each stage 646
Tumor localization Distal stomach Proximal stomach (Cardia) Time to diagnosis 1999-2002 2003-2006 2007-2010 Stage Stage I Stage II Stage III Stage IV
P
Relative survival HR (%95 CI)
0.019 1 1.3 (1.1-1.7) 0.01 1.37 (1.14-1.78) 1.17 (0.9-1.4) 1 0.001 1 3.6 (1.09-4.1) 9.4 (2.98-12.3) 31.6(10-42)
HR=Hazard ratio, CI=Confidence interval
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1999 to 2010. When compared to SEER data involving the time period from 1999 to 2003, median age of our cohort was found to be 14 years younger than American patients.[9] Furthermore, the ratio of patients whose median age was 70 years have been increased from 9.8% (between the years 1999 and 2002) to 20% (between 2007 and 2010). However, this increased ratio of the patients older than 70 years, the age subgroups in our study were not found independent prognostic factors on relative survival. It may be because that our cohort had only determined cancer specific survival. The limitation of this study was that no survival and comorbid related events were available. In contrast to the decreasing overall stomach cancer incidence rates (distal stomach), cancer of cardia (proximal part of the stomach) incidence rates have increased in the US and in many European countries, including Denmark and United Kingdom.[7,8] Furthermore, proximal gastric carcinoma tends to be more aggressive than those arising from distal sites. Environmental factors or chemical carcinogens may be more strongly associated with cardiac carcinomas compared to more distal carcinomas.[16] The main risk factors of gastric cancer, namely, cardia tumor; include smoking, gastro-esophageal reflux, obesity and the presence of Barrett’s esophagus and gender. Despite the fact that the etiology of these groups of cancer is insufficiently known.[17,18] It is known that Helicobacter pylori is a mainly risk factor of distal gastric cancer. H. pylori increases the risk of gastric cancer six times. Eradication of H. pylori infection results in decreased incidence of distal gastric cancer.[19,20] In the current study, the proportion of cardia-localized gastric adenocarcinoma increased from 7.2% to 22.5% during the period from 1999 to 2010. Our study also has shown that proximal gastric carcinoma caused death 1.3 times than that of distal sites. Most patients with gastric cancer in US have advanced incurable disease at the time of presentation. At diagnosis, approximately 50% have a disease that extends beyond locoregional confines, but in Japan this ratio was diverse.[21] In the current study, approximately 75% of patients have stage III and IV disease at the time of diagnosis. However, stage I and II gastric adenocarcinoma ratio increased between 1999 and 2010. In our cohort, local advanced and metastatic disease presentation was much more than early gastric carcinoma. Since our hospital was tertiary medical center, this ratio may cause selective bias compared on normal population. The incidence of the intestinal type gastric adenocarcinoma ratio decreased world-wide.[22] In contrast, the incidence of diffuse type gastric carcinoma has been increasing.[23] In the same prior report from the current study, the incidence rate of intestinal adenocarcinoma decreased and the rate of diffuse type increased. However, the major adenocarcinoma subtype was the intestinal type (59%-65%).
The world-wide incidence of gastric cancer has declined rapidly over the recent few decades.[4-6,24] Part of the decline may be due to the recognition of certain risk factors such as H. pylori and other dietary and environmental risks.[25-27] Gastric cancer relative survival improved also world-wide and this situation may be related with improved diagnosis and treatment and also screening and early detection like in Japan in which gastric cancer incidence is high.[4-6,24,28-31] Lambert et al. showed that the incidence and mortality rates declined in Japan, US and Slovenia in the period from 1975 to 1995. They also have shown that localized gastric cancer ratio increased in US and Japan.[24] In the current study, relative survival rate significantly improved in stage I and II and slightly improved in stage III but remained unchanged in stage IV between 1999 and 2010. We also demonstrated that the ratio of death in patients whose diagnosis was established between 1999 and 2010 was 1.37 times higher than that of patients who had been diagnosed between 2007 and 2010. For gastric cancer, cancer relative survival increased between 1999 and 2010 which may be due to improved diagnosis and treatment modality. In Turkey, besides breast and cervical cancer screenings, colorectal, and stomach cancer screening programs may be detecting early gastric cancer and increased relative survival gastric cancer.[32] In conclusion, median age of diagnosis and the ratio of older patients and proximal gastric adenocarcinoma, diffuse histologic subtype increased between 1999 and 2010. Furthermore, advanced gastric carcinoma ratio was higher than early stage, but early stage ratio has increased between 1999 and 2010. Cancer related survival significantly improved for stage I and stage II and at also slightly improved for stage III, but remained unchanged for stage IV. Proximal stomach localization had significantly poor outcome on relative survival and tumor localization of gastric cancer has been changed according to epidemiological factors. This should be considered before diagnosis and treatment. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61:212-36. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010;19:1893-907. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993;54:594-606. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001;37:S4-66. Parkin DM. International variation. Oncogene 2004;23:6329-40. Botterweck AA, Schouten LJ, Volovics A, Dorant E, van Den Brandt PA. Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol 2000;29:645-54. Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998;83:2049-53.
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Hayat MJ, Howlader N, Reichman ME, Edwards BK. Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program. Oncologist 2007;12:20-37. Fritz A, Percy C, Jack A, Shanmugarathnam K, Sobin L, Parkin DM, et al. International Classification of Diseases for Oncology. 3rd ed. Geneva: World Health Organization; 2000. Lauren P. The two hıstologıcal maın types of gastrıc carcınoma: Dıffuse and so-called ıntestınal-type carcınoma. An attempt at a hıstoclınıcal classıfıcatıon. Acta Pathol Microbiol Scand 1965;64:31-49. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917. Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: A global overview. Int J Cancer 2009;125:666-73. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 2010;46:765-81. Kalish RJ, Clancy PE, Orringer MB, Appelman HD. Clinical, epidemiologic, and morphologic comparison between adenocarcinomas arising in Barrett’s esophageal mucosa and in the gastric cardia. Gastroenterology 1984;86:461-7. Dolan K, Sutton R, Walker SJ, Morris AI, Campbell F, Williams EM. New classification of oesophageal and gastric carcinomas derived from changing patterns in epidemiology. Br J Cancer 1999;80:834-42. Rusch VW. Are cancers of the esophagus, gastroesophageal junction, and cardia one disease, two, or several? Semin Oncol 2004;31:444-9. Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 1998;114:1169-79. Jézéquel J, Bessaguet C, Verveur C, Faycal J, Richert Z, Metges JP, et al. Trends in incidence, management, and survival of gastric and cardia carcinomas in the area of Finistere (France) between 1984 and 2003. Eur J Gastroenterol Hepatol 2010;22:1412-9. Noguchi Y, Yoshikawa T, Tsuburaya A, Motohashi H, Karpeh MS, Brennan MF. Is gastric carcinoma different between Japan and the United States? Cancer 2000;89:2237-46.
22. Kaneko S, Yoshimura T. Time trend analysis of gastric cancer incidence in Japan by histological types, 1975-1989. Br J Cancer 2001;84:400-5. 23. Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: Increase in the signet ring cell type. Arch Pathol Lab Med 2004;128:765-70. 24. Lambert R, Guilloux A, Oshima A, Pompe-Kirn V, Bray F, Parkin M, et al. Incidence and mortality from stomach cancer in Japan, Slovenia and the USA. Int J Cancer 2002;97:811-8. 25. La Vecchia C, Chatenoud L, Franceschi S, Soler M, Parazzini F, Negri E. Vegetables and fruit and human cancer: Update of an Italian study. Int J Cancer 1999;82:151-2. 26. Navarro Silvera SA, Mayne ST, Risch H, Gammon MD, Vaughan TL, Chow WH, et al. Food group intake and risk of subtypes of esophageal and gastric cancer. Int J Cancer 2008;123:852-60. 27. González CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti M, Boeing H, et al. Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Cancer 2006;118:2559-66. 28. Shibata A, Parsonnet J. Stomach cancer. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press; 2006. p. 707-20. 29. La Vecchia C, Franceschi S. Nutrition and gastric cancer. Can J Gastroenterol 2000;14:51D-4. 30. Boffetta P, La Vecchia C. Neoplasms. In: Oxford Textbook of Public Health. Oxford, UK: Oxford University Press; 2009. In press. 31. Lau M, Le A, El-Serag HB. Noncardia gastric adenocarcinoma remains an important and deadly cancer in the United States: Secular trends in incidence and survival. Am J Gastroenterol 2006;101:2485-92. 32. Yılmaz HH, Yazıhan N, Tunca D, Sevinç A, Olcayto EÖ, Ozgül N, et al. Cancer trends and incidence and mortality patterns in Turkey. Jpn J Clin Oncol 2011;41:10-6. Cite this article as: Tural D, Selçukbiricik F, Akar E, Serdengeçti S, Büyükünal E. Gastric cancer: A case study in Turkey. J Can Res Ther 2013;9:644-8. Source of Support: Nil, Conflict of Interest: None declared.
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Gastric cancer: A case study in Turkey ABSTRACT Objective: The aim of this study was to determine age-specific incidence ratios, gastric cancer localization trend, histologic subtype and cancer related survival that whether have changed during the period from 1999 to 2010. Materials and Methods: A total of 866 gastric cancer patients treated at the hospital were retrospectively evaluated. Categorical and continuous variables were summarized using descriptive statistics and were compared using the Chi-square and Mann-Whitney U-tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: The median age at diagnosis was 58 years. Trends concerning the median ages of the patients were increased (from 57 years to 59 years). The proportion of diffuse histological subtype gastric adenocarcinoma increased during the period from 1999 to 2010, and it was 27% between 1999 and 2002 and 32% between 2007 and 2010 (P = 0.04). The proportion of gastric adenocarcinoma localized in cardia increased during the period from 1999 to 2010, and was 7.2% between 1999 and 2002; and 22.5% in 2007 and 2010 (P = 0.004). For stage I that was diagnosed between 1999 and 2002, the relative survival was 67% and in patients diagnosed between 2007 and 2010 the rate was 85%. For stage II that was diagnosed between 1999 and 2002, the relative survival was 35% and in patients diagnosed between 2007 and 2010, the rate was 65%. Cox regression analysis was conducted based on age subgroup, diagnosis time, and gastric localization (proximal/distal) and for adenocarcinoma subtypes. Hazard ratio was 31.6 for stage IV (confidence interval [CI] = 10-42), 1.3 for cardia localization (CI = 1.04-1.6) and 1.37 for patients who had been diagnosed between 1999 and 2002 (1.14-1.78). Conclusions: The ratio of median age at diagnosis and proximal gastric adenocarcinoma, diffuse histologic subtype increased between 1999 and 2010. Cancer related survival significantly improved for stage I and stage II. Cardia localization and time of diagnosis between 1999 and 2002 had significantly poor outcome on relative survival. KEY WORDS: Gastric cancer, intestinal and diffuse subtype, proximal/distal ratio, stages and survival
INTRODUCTION Incidence and mortality rates for most cancers are decreasing in the United States (US) and other more developed western countries.[1,2] Although much progress has been made in reducing mortality rates, stabilizing incidence rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85.[3] Increases are expected in the future because of long life expectancy. Cancer has increasingly become a common problem for older people due to the prolonged life expectancy of the general population.
Gastric cancers have also increased with age, especially in elderly people.[9] Gastric cancer in older persons has increasingly become a common problem in the last years. Data of 866 patients were collected from hospital based registries from 1999 to 2010. The aim of this study was to determine age specific incidence ratios, gastric cancer localization trend (proximal/ distal), gastric cancer histologic subtype at the stage of diagnosis and cancer relative survival that have changed during the period from 1999 to 2010.
Deniz Tural1, Fatih Selçukbiricik2, Emre Akar2, Süheyla Serdengeçti3, Evin Büyükünal2 Department of Internal Medicine, Division of Medical Oncology, Akdeniz University, School of Medicine, Antalya, Turkey, 2Departments of Internal Medicine, Division of Medical Oncology, Istanbul University, Cerrahpaşa Medical Faculty, Istanbul, Turkey, 3 Medical Student, Istanbul University, Cerrahpaşa Medical Faculty, Istanbul, Turkey 1
For correspondence: Dr. Emre Akar, Istanbul University, Cerrahpasa Medical Faculty, TR-34098 Istanbul, Turkey. E-mail: emrevonakar@ gmail.com
Overall gastric cancer incidence and mortality are decreasing world-wide. However, despite its recent decline, gastric cancer is the fourth most common cancer and the second leading cause of cancerrelated deaths world-wide.[4-6] In contrast to the decreasing overall gastric cancer incidence rates (distal stomach), incidence rates have increased for cancer of cardia (proximal part of the stomach) in the US and many European countries, including Denmark and United Kingdom.[7,8]
Gastric cancer patients treated in our hospital between 1999 and 2010 were retrospectively evaluated. Cancer was coded according to the International Classification of Disease for Oncology, 3rd edition.[10] We included only gastric adenocarcinoma in this study. Patients were included when adenocarcinoma of the stomach was histologically confirmed and survival data were
644
Journal of Cancer Research and Therapeutics - October-December 2013 - Volume 9 - Issue 4
MATERIALS AND METHODS Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.126466 PMID: 24518710 Quick Response Code:
Tural, et al.: Patterns of gastric cancer in Turkey altered
available. Patients were excluded when a tumor other than adenocarcinoma was histologically identified. We divided cases into two subgroups based on anatomic localization in the stomach; as Group 1: Proximal stomach (cardia) and Group 2: Noncardia (gastric antrum, pylorus, lesser curvature and greater curvature of the stomach).[8] After we determined the ages of each cancer patient, number of cancer cases were categorized into two age groups; those 70 years old or younger than 70 years of age and older than 70 years. The cases were divided into three groups based on histopathological subtype: Group 1; intestinal gastric cancer and Group 2; diffuse gastric cancer and Group 3; mixed adenocarcinoma.[11] Gastric adenocarcinoma stage was determined according to the seventh edition of the International Union Against Cancer guidelines. Statistical analysis Categorical and continuous variables were summarized using the descriptive statistics (e.g., median, range, frequency, and percentage) and compared with Chi-square and Mann-Whitney U-tests, respectively. The median age rates between 1999 and 2010 for five age groups were calculated for 1 year period and 4 years periods. Proximal/distal gastric ratios, intestinal/diffuse adenocarcinoma ratios, at-diagnosis stage and cancer specific survival were calculated for 4 years periods. Cancer specific survival rates were estimated by the KaplanMeier method and cancer relative survival was calculated from the date of diagnosis until death from gastric adenocarcinoma. We evaluated the effect of five age groups, tumor localization (proximal/distal), diagnosis time, histologic subtype and stage on relative survival by Cox regression analyzes. All analyzes were performed using the SPSS 15.0 (SPSS Inc., Chicago, IL, USA) software. The statistical level of significance was defined as P < 0.05.
Table 1: The demographic data of 866 patients with gastric cancer Variable Gender Male Female Median age (range) Time to diagnosis age >70 year 70 yearde Histology Diffuse adenocarcinoma Intestinal adenocarcinoma Mixed adenocarcinoma Stomach localization Cardia part Distal part Time to diagnosis stage Stage I Stage II Stage III Stage IV
N (%) 606 (70) 260 (30) 58 (22-90) 151 (17) 715 (83) 265 (30) 536 (62) 65 (8) 158 (18) 708 (82) 80 (9) 150 (16) 212 (25) 424 (50)
Figure 1: The changes of the annual values rates of patients older than 70 years are shown in 1-year periods between 1999 and 2010
RESULTS Details of tumor characteristic are shown Table 1 between 1999 and 2010, there were 866 cases of gastric adenocarcinoma recorded in hospital based registries. The median age at diagnosis was 58 years (range = 22-90). When compared to Surveillance, Epidemiology and End Results (SEER) data consisting of the time period from 1999 to 2003, median age of our cohort was found to be younger than American patients.[9] The median age was 57 years during 1999-2002 period, 58 years between 2003 and 2006 and 59 years between 2007 and 2010. Gastric adenocarcinoma in patients older than 70 years increased between 1999 and 2010. Between 1999 and 2002, the ratio of patients who were older than 70 years was 9.8%. This ratio increased and between 2007 and 2010, 20% were older than 70 years (P = 0.001). The changes of the rates of annual values for patients older than 70 years are shown in Figure 1.
Figure 2: The proportion of cardia (proximal stomach) adenocarcinoma increased between 1999 and 2010
The proportion of gastric adenocarcinoma localized in cardia, increased during the period from 1999 to 2010, and was 7.2% between 1999 and 2002; and 22.5% in 2007-2010 (P = 0.004). The details of proximal/distal stomach ratio are shown in Figure 2. Stage III and stage IV constituted the dominant proportion in the time of diagnosis, but stage I and II gastric adenocarcinoma
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Tural, et al.: Patterns of gastric cancer in Turkey altered
increased from 15% to 25% between 1999 and 2010. The details of stage changed during 1999-2010 are demonstrated in Figure 3. The proportion of diffuse histological subtype gastric adenocarcinoma increased during the period from 1999 to 2010, and it was 27% between 1999 and 2002 and 32% between 2007 and 2010. The ratio of intestinal adenocarcinoma also decreased (from 65% to 59%) and this difference was statistically significant (P = 0.04) [Figure 4].
and 2002, the relative survival was 4% (95% CI = 3-5%) and this ratio remained the same (95% CI = 3.5-5%) for patients who were diagnosed between 2007 and 2010. The details of the relative survival ratio changes are shown in Figure 5. Cox regression analysis was conducted, based on age subgroup, diagnosis time, and gastric localization (proximal/distal), and for adenocarcinoma subtypes. Hazard ratio was 31.6 for stage IV (CI = 10-42), 1.3 for cardia localization (CI = 1.04-1.6) and 1.37 for patients who had been diagnosed between 1999 and 2002 (1.14-1.78). Details of Cox regression analysis are shown in the Table 2.
For stage I diagnosed between the years 1999 and 2002, the relative survival was 67% (95% confidence interval [CI] = 63-71%) and 85% (95% CI = 80-90%) for patients who were diagnosed during 2007-2010 and for stage II diagnosed between 1999 and 2002, the relative survival was 35% (95% CI = 31-39%) and that diagnosed between 2007 and 2010 was 65% (95% CI = 61-69%). Relative survival improved both for stages I and II during 1999-2010. For stage III diagnosed between 1999 and 2002, the relative survival was 15% (95% CI = 13-17%) and that diagnosed between 2007 and 2010 was 21% (95% CI = 17-25%) and this ratio was statistically not significant (P = 0.12). For stage IV diagnosed between 1999
Gastric cancer is the fourth most commonly diagnosed cancer. [12] However, incidence rates for gastric cancer have decreased worldwide.[4-6,13,14] Currently, gastric cancer is the second leading cause of cancer related death in both men and women. [12-15] Gastric cancers also have increased with age, especially in elderly[9] gastric cancer in older people has increasingly become a common problem in the recent years. In the current study, median age increased from 57 to 59 during the period from
Figure 3: Changed proportion of stage between 1999–2010.
Figure 4: Diffuse adenocarcinoma/intestinal adenocarcinoma ratio
DISCUSSION
Table 2: Results of cox regression analysis for the association between relative survival and diagnosis time, age groups, tumor localization and tumor histological subtype, between 1999 and 2010 Variable
Figure 5: Between 1999 and 2010, change in the relative survival ratio for each stage 646
Tumor localization Distal stomach Proximal stomach (Cardia) Time to diagnosis 1999-2002 2003-2006 2007-2010 Stage Stage I Stage II Stage III Stage IV
P
Relative survival HR (%95 CI)
0.019 1 1.3 (1.1-1.7) 0.01 1.37 (1.14-1.78) 1.17 (0.9-1.4) 1 0.001 1 3.6 (1.09-4.1) 9.4 (2.98-12.3) 31.6(10-42)
HR=Hazard ratio, CI=Confidence interval
Journal of Cancer Research and Therapeutics - October-December 2013 - Volume 9 - Issue 4
Tural, et al.: Patterns of gastric cancer in Turkey altered
1999 to 2010. When compared to SEER data involving the time period from 1999 to 2003, median age of our cohort was found to be 14 years younger than American patients.[9] Furthermore, the ratio of patients whose median age was 70 years have been increased from 9.8% (between the years 1999 and 2002) to 20% (between 2007 and 2010). However, this increased ratio of the patients older than 70 years, the age subgroups in our study were not found independent prognostic factors on relative survival. It may be because that our cohort had only determined cancer specific survival. The limitation of this study was that no survival and comorbid related events were available. In contrast to the decreasing overall stomach cancer incidence rates (distal stomach), cancer of cardia (proximal part of the stomach) incidence rates have increased in the US and in many European countries, including Denmark and United Kingdom.[7,8] Furthermore, proximal gastric carcinoma tends to be more aggressive than those arising from distal sites. Environmental factors or chemical carcinogens may be more strongly associated with cardiac carcinomas compared to more distal carcinomas.[16] The main risk factors of gastric cancer, namely, cardia tumor; include smoking, gastro-esophageal reflux, obesity and the presence of Barrett’s esophagus and gender. Despite the fact that the etiology of these groups of cancer is insufficiently known.[17,18] It is known that Helicobacter pylori is a mainly risk factor of distal gastric cancer. H. pylori increases the risk of gastric cancer six times. Eradication of H. pylori infection results in decreased incidence of distal gastric cancer.[19,20] In the current study, the proportion of cardia-localized gastric adenocarcinoma increased from 7.2% to 22.5% during the period from 1999 to 2010. Our study also has shown that proximal gastric carcinoma caused death 1.3 times than that of distal sites. Most patients with gastric cancer in US have advanced incurable disease at the time of presentation. At diagnosis, approximately 50% have a disease that extends beyond locoregional confines, but in Japan this ratio was diverse.[21] In the current study, approximately 75% of patients have stage III and IV disease at the time of diagnosis. However, stage I and II gastric adenocarcinoma ratio increased between 1999 and 2010. In our cohort, local advanced and metastatic disease presentation was much more than early gastric carcinoma. Since our hospital was tertiary medical center, this ratio may cause selective bias compared on normal population. The incidence of the intestinal type gastric adenocarcinoma ratio decreased world-wide.[22] In contrast, the incidence of diffuse type gastric carcinoma has been increasing.[23] In the same prior report from the current study, the incidence rate of intestinal adenocarcinoma decreased and the rate of diffuse type increased. However, the major adenocarcinoma subtype was the intestinal type (59%-65%).
The world-wide incidence of gastric cancer has declined rapidly over the recent few decades.[4-6,24] Part of the decline may be due to the recognition of certain risk factors such as H. pylori and other dietary and environmental risks.[25-27] Gastric cancer relative survival improved also world-wide and this situation may be related with improved diagnosis and treatment and also screening and early detection like in Japan in which gastric cancer incidence is high.[4-6,24,28-31] Lambert et al. showed that the incidence and mortality rates declined in Japan, US and Slovenia in the period from 1975 to 1995. They also have shown that localized gastric cancer ratio increased in US and Japan.[24] In the current study, relative survival rate significantly improved in stage I and II and slightly improved in stage III but remained unchanged in stage IV between 1999 and 2010. We also demonstrated that the ratio of death in patients whose diagnosis was established between 1999 and 2010 was 1.37 times higher than that of patients who had been diagnosed between 2007 and 2010. For gastric cancer, cancer relative survival increased between 1999 and 2010 which may be due to improved diagnosis and treatment modality. In Turkey, besides breast and cervical cancer screenings, colorectal, and stomach cancer screening programs may be detecting early gastric cancer and increased relative survival gastric cancer.[32] In conclusion, median age of diagnosis and the ratio of older patients and proximal gastric adenocarcinoma, diffuse histologic subtype increased between 1999 and 2010. Furthermore, advanced gastric carcinoma ratio was higher than early stage, but early stage ratio has increased between 1999 and 2010. Cancer related survival significantly improved for stage I and stage II and at also slightly improved for stage III, but remained unchanged for stage IV. Proximal stomach localization had significantly poor outcome on relative survival and tumor localization of gastric cancer has been changed according to epidemiological factors. This should be considered before diagnosis and treatment. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61:212-36. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010;19:1893-907. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993;54:594-606. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001;37:S4-66. Parkin DM. International variation. Oncogene 2004;23:6329-40. Botterweck AA, Schouten LJ, Volovics A, Dorant E, van Den Brandt PA. Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol 2000;29:645-54. Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998;83:2049-53.
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22. Kaneko S, Yoshimura T. Time trend analysis of gastric cancer incidence in Japan by histological types, 1975-1989. Br J Cancer 2001;84:400-5. 23. Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: Increase in the signet ring cell type. Arch Pathol Lab Med 2004;128:765-70. 24. Lambert R, Guilloux A, Oshima A, Pompe-Kirn V, Bray F, Parkin M, et al. Incidence and mortality from stomach cancer in Japan, Slovenia and the USA. Int J Cancer 2002;97:811-8. 25. La Vecchia C, Chatenoud L, Franceschi S, Soler M, Parazzini F, Negri E. Vegetables and fruit and human cancer: Update of an Italian study. Int J Cancer 1999;82:151-2. 26. Navarro Silvera SA, Mayne ST, Risch H, Gammon MD, Vaughan TL, Chow WH, et al. Food group intake and risk of subtypes of esophageal and gastric cancer. Int J Cancer 2008;123:852-60. 27. González CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti M, Boeing H, et al. Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Cancer 2006;118:2559-66. 28. Shibata A, Parsonnet J. Stomach cancer. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press; 2006. p. 707-20. 29. La Vecchia C, Franceschi S. Nutrition and gastric cancer. Can J Gastroenterol 2000;14:51D-4. 30. Boffetta P, La Vecchia C. Neoplasms. In: Oxford Textbook of Public Health. Oxford, UK: Oxford University Press; 2009. In press. 31. Lau M, Le A, El-Serag HB. Noncardia gastric adenocarcinoma remains an important and deadly cancer in the United States: Secular trends in incidence and survival. Am J Gastroenterol 2006;101:2485-92. 32. Yılmaz HH, Yazıhan N, Tunca D, Sevinç A, Olcayto EÖ, Ozgül N, et al. Cancer trends and incidence and mortality patterns in Turkey. Jpn J Clin Oncol 2011;41:10-6. Cite this article as: Tural D, Selçukbiricik F, Akar E, Serdengeçti S, Büyükünal E. Gastric cancer: A case study in Turkey. J Can Res Ther 2013;9:644-8. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Cancer Research and Therapeutics - October-December 2013 - Volume 9 - Issue 4
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