Cancer Information and Epidemiology Division, Research Institute, National Cancer Center, Tokyo
Correspondence: Ying Liu, Cancer Information and Epidemiology Division, Research Institute, National Cancer Center, Tokyo1040045, Japan. E-mail: yliu{at}gan2.res.ncc.go.jp
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Abstract |
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Methods The stomach was anatomically divided into the upper, middle, and lower thirds. Age- and sex-specific incidences by tumour location were estimated by multiplying the age- and sex-specific national incidences of gastric cancer by the corresponding proportions of tumour location. We studied 171 721 cases of gastric cancer from the Gastric Cancer Registry of Japan.
Results Over 15 years, the proportion of tumours in the upper third of the stomach increased in men but did not change much in women. The proportion of tumours in the middle third of the stomach increased among both men and women while the proportion of tumours in the lower third of the stomach decreased among both men and women. The incidence of tumours in the upper third of the stomach showed an increasing trend among elderly men and women but not among young ones. The incidence of tumours in the lower third of the stomach decreased significantly among men and women of most age groups.
Conclusions The present study added evidence of disparate trends in the incidence of gastric cancer by tumour location. The separate epidemiological features may indicate different aetiologies as well as changes in the degree of influence of these aetiologies.
Accepted 15 October 2003
The incidence rate of gastric cancer has declined from half a century ago. However, contrary to the general trend of steady decline in the incidence of gastric cancer, many western countries have noticed in recent decades an increase in gastric cancer of the cardia,16 a location associated with a less favourable outcome. Although Japan has the highest national incidence of gastric cancer, evidence of changes in gastric cancer by tumour location is limited,79 and whether there is an absolute increase in incidence or only a relative increase in relation to stomach cancer at other sites remains unknown. This study was performed to estimate the incidence of gastric cancer by tumour location and to clarify whether the relative and absolute rates of gastric cancer by tumour location have changed in Japan between 1975 and 1989.
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Methods |
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We found 178 252 registered cases 30 years of age and who were initially diagnosed between 1975 and 1989. We excluded 4634 of these cases because of incomplete information regarding tumour location and 1897 more cases that involved tumours classified as being other than gastric cancer (e.g. malignant lymphoma) according to the International Classification of Diseases (9th Edn). Thus, 171 721 cases involving 111 974 men and 59 747 women were left for analysis. Of these patients, 95% underwent surgical treatment.
Tumour location
In this registry, the subsites of gastric carcinoma were classified as cardia, fundus, body, lesser curvature, greater curvature, pylorus, or pyloric antrum, and specified as located in the upper, middle, or lower third of the stomach. Cardia carcinoma has been defined in various ways,12 and until quite recently in Japan, the upper third of the stomach has been called the cardia based on the guidelines for gastric cancer classification.13 Because of the difficulty in distinguishing the actual cardia from the upper third of the stomach, we considered both defined areas to be one site for analysis in our study. According to the latest guidelines for gastric cancer classification,14 the stomach is anatomically delineated into the upper, middle, and lower thirds by dividing the lesser and greater curvatures at two equidistant points and joining these points. Tumours located predominantly in the gastro-oesophageal junction and cardia were determined to be in the upper third of the stomach; those located in the pylorus were considered to be in the lower third of the stomach; and those located in the midbody were determined to be in the middle third of the stomach. If a tumour was located across adjacent regions, the region containing the greater proportion of the tumour was considered to be the tumour's location. If a tumour spanned all three regions, its location was classified as being the entire body of the stomach.
Estimation of the incidence of gastric cancer by tumour location
Annual proportional frequencies of gastric cancer by tumour location were calculated for each sex and 10-year age group (from 3039 years old to those 70 years). Annual age-specific incidence rates of gastric cancer by tumour location were estimated by multiplying the national incidence rates of gastric cancer in the relevant year15 by the proportional frequencies of gastric cancer by tumour location for each sex and 10-year age group.
Statistical analysis
The years from 1975 to 1989 were considered as three groups: 19751979, 19801984, 19851989. The change over time in the proportion of tumours by location was tested by Mantel-Haenszel 2 analysis. We used a logistic regression model to analyse the percentage of average increase or decrease per year in the incidence rates of gastric cancer by tumour location with 95% CI. By fitting a logistic regression model, time trends stratified by age group were analysed with disease status as a dependent variable and time in years as an independent variable. The results for linear trend analysis were presented by percentage of increase in incidence rate per year (% increase). Statistical analyses were performed with the SASTM software package, version 8.2 (SAS Institute, Inc., Cary, NC, USA).
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Although the limitations described above may exist, and further studies that include autopsy data are needed to confirm our findings, this registry system is the only one covering all of Japan, and with its large sample size, no more precise data are available. To our knowledge, this is the first study from Japan that provided data on the change over time of the incidences of gastric cancer by tumour location, and gave information on age- and sex-specific time trends.
The present study has not provided any evidence regarding changes in the incidence rate or proportion of cancer of the gastric cardia, which is a relatively small yet distinct part of the proximal third of the stomach. The present study added evidence of disparate trends in the incidences of proximally localized and other gastric adenocarcinomas, by showing a decreasing incidence of distal gastric cancer and an increasing incidence of proximal gastric adenocarcinoma. The findings of the present study are in agreement with those of two previous Japanese studies, which found a relatively increasing incidence of cardia or proximally localized gastric adenocarcinoma.7,8 However, these previous Japanese studies were based on the proportional frequency ratio of gastric cancers by tumour location, which does not itself indicate trends of incidence. In addition, information on age-specified time trend, which might be informative for evaluating whether exposure status to relevant environmental factors differed between age groups, is scarce2 and has not been reported in previous Japanese studies. The findings indicated not only a proportional increase but also an actual increase in the incidence of proximal gastric adenocarcinoma among elderly men and women but not among young people. The findings also indicated an actual decrease in the incidence of distal gastric adenocarcinoma and no change in the incidence of gastric cancer in the middle third of the stomach among men and women of almost all ages.
The disparate epidemiological traits of gastric cancer by tumour location may suggest different aetiologies. However, the cause of changes in proportional rate and incidence rate over time is not well understood. An increasingly western lifestyle as well as a decreased incidence of Helicobacter pylori infection17,18 may contribute to the change over time in the incidence of gastric cancer by tumour location. Infection with H. pylori has been identified as an important risk factor for gastric cancer.19,20 The effects of H. pylori on tumour development vary by anatomical site. A large amount of evidence suggests that the decreasing prevalence of H. pylori infection, especially with cagA+ strains, may be associated with the declining incidence of distal gastric adenocarcinomas.5,2123 The decreased infection rate of H. pylori may contribute to the increasing incidence of proximal adenocarcinomas as well. Several recent studies have noted that treating H. pylori infection might increase the risk of peptic oesophagitis and adenocarcinoma of the oesophagus and cardia,24,25 although the protective effect of H. pylori against cardia tumours remains controversial.26,27
In addition to H. pylori infection, changes in lifestyle may be responsible for the diverging incidence rates of gastric cancer by tumour location. A study that investigated the incidence of gastric carcinoma in Asian immigrants to the US and their descendants indicated that dietary and other lifestyle differences between the different generations of Japanese-Americans, and between Japanese residents of the US and those of Japan may provide clues regarding the aetiologies of stomach cancers that arise beyond the gastric cardia.28 Some studies have attempted to interpret the diverging incidence rates by tumour location through an association with dietary antioxidants,29 fruit and vegetable consumption,30 cigarette smoking,31,32 and an increasing prevalence of obesity.33 Moreover, the Epstein-Barr virus (EBV) has been found to be associated with cardia tumours; when the antrum was used as a referent category, the risk of tumours in the cardia increased five times.34
Several studies found different rates of gene mutation according to tumour location, suggesting variation in susceptibility and different mechanisms in the pathogenesis of stomach cancer by location.35,36 Japanese studies noted that familial gastric cancers were frequently located in the cardia and that those appeared to be more aggressive than sporadic gastric cancers. The unique characteristics of familial gastric cancer suggests a genetic component as well as an environmental influence in its aetiology.37,38 Westernization of lifestyle, the consistently decreasing H. pylori infection rate among young people, and possible changes in geneenvironment interactions may contribute to the increased incidence of proximal gastric adenocarcinomas.
Gastric cancer among young patients was less likely to be found in the proximal part of the stomach and in the antrum than in the gastric body.39 In the present study, the relative proportion of distal tumours was about half that of tumours in the middle third of the stomach among young patients. However, the relative proportion of distal tumours increased with increasing age and was twice that of tumours in the middle third of the stomach among patients 80 years. This finding suggests that aetiological factors among young patients are different from those among elderly ones. In addition, the moderately decreasing rate over time in the age-specific incidence of proximal tumours among young patients compared with the increasing rate among elderly ones may strengthen this assumption. Two European studies have shown that the early onset of gastric cancers, especially in patients
40 years, is more often associated with genetic changes at preferential chromosomal loci compared with those of older patients, suggesting a difference in genetic predisposition between age groups.40,41 The effects of rapidly changing environmental factors accumulated over a long time period may be more pronounced among older age groups than younger ones. Remarkable lifestyle changes in Japan from the middle of the 20th century, and their possible interaction with genetic susceptibility, may partially explain why changes in trends are more common among the older age groups than the younger age groups. No previous Japanese studies have differentiated the change over time in the incidence of proximal gastric cancer between men and women. The present study found no remarkable differences in changes over time in the incidence of subsite-specific gastric cancer among men and women. The similarity of the trends suggests that the aetiological influences did not vary between men and women over the 15-year period.
The separate epidemiological features of gastric cancer by tumour location may indicate different aetiologies as well as changes in the degree of influence of these aetiologies. Because little is known about the aetiology of proximal adenocarcinomas, and because not only the relative incidence rate but also the absolute incidence rate seems to be rising, further research into gastric adenocarcinomas by tumour location is urgently needed to clarify the risk factors and mechanisms responsible for the increasing incidence.
KEY MESSAGES
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References |
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