Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Enrichment of Combined Antral and Corpus Atrophic Gastritis (“Combined AG”) in Sibs of Gastric Carcinoma Patients M. Kekki, M. Siurala & T. Ihamäki To cite this article: M. Kekki, M. Siurala & T. Ihamäki (1991) Enrichment of Combined Antral and Corpus Atrophic Gastritis (“Combined AG”) in Sibs of Gastric Carcinoma Patients, Scandinavian Journal of Gastroenterology, 26:sup186, 24-28, DOI: 10.3109/00365529109103983 To link to this article: http://dx.doi.org/10.3109/00365529109103983
Published online: 08 Jul 2009.
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Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [RMIT University Library]
Date: 17 March 2016, At: 02:57
Enrichment of Combined Antral and Corpus Atrophic Gastritis ("Combined AG") in Sibs of Gastric Carcinoma Patients M. KEKKI, M. SIURALA, & T. IHAMAKI Second Dept. of Medicine, University of Helsinki, Helsinki, Finland
Downloaded by [RMIT University Library] at 02:57 17 March 2016
M. Kekki. M. Siurala, T. Ihamaki. Enrichment of combined antral and corpus atrophic gastritis ("combined AG") in sibs ofgastric carcinoma patients. Scand J Gastroenterol 1991,26(suppl 186), 24-28 The Occurrence of differcnt combinations of antral and corpus atrophic gastritis (AG) was studied in 127 sibs and IS9 children of 73 gastric carcinoma patients. Scventy-three control probands, age- and sex-matched for the carcinoma probands, and their 379 first-degree relatives were uscd as controls. Sibs of gastric carcinoma patients revealed a significant enrichment of AG affecting simultaneously both antrum and corpus (combined AG), while no such enrichment could be demonstrated in children, who behaved on the whole similarly to the controls. In addition, sibs of gastric carcinoma patients showed a significant aggregation of combined AG also when compared with children of similar age. This suggests that genetic factors in addition to environmental ones participate in the accumulation of combined AG in sihs. The lack of phenotype AB in children excludes the possibility of dominant Mendelian inheritance, hut leavcs the possibility of a recessive autosomal or multigenetic inheritance. The enrichment of combined AG in sibs of gastric carcinoma patients could be one of the factors involved in the increased liability of close relatives of gastric carcinoma patients to contract gastric malignancy.
K q words: Gastritis; family study; gastric cancer relativcs Matti Kekki. M.D.,Second Dept. of Medicine, Universitv of Helsinki. SF-OOZY0 Helsinki, Finland
Atrophic gastritis (AG) affecting simulta- places of birth and residence, are used as neously antrum and body ("combined AG", controls. called by Glass AB-gastritis; 1) is commonly found in patients with gastric carcinoma (2-7) MATERIAL AND METHODS and seems to carry an increased risk of underlying malignancy. According to our recent calcu- Series The series consists of 301 first-degree relatives lations (8) the risk of getting gastric carcinoma is significantly increased in the final stages of of 73 consecutive and histologically verified atrophic gastritis, particularly those of antral cases of gastric carcinoma diagnosed at the mucosa. In the combined forms of AG the risk Gastroenterological Unit, Second Department of is presumably still higher: it represents the Medicine, University of Helsinki, Helsinki, multiplicand of risks due to antral and body AG Finland. Of the 30 1 relatives adequate biopsies (8). For this reason one could anticipate an were available from 286 subjects of whom 127 enrichment of this form of AG in different risk were sibs and 159 were children of the index conditions of gastric carcinoma, such as close patients. The composition of the series and relatives of patients with this disease (9-1 I). The controls and their mean age and sex distribution present paper deals with the occurrence of are given in Table 1. Sibs and children have been combined AG in sibs and children of gastric treated separately throughout the study because carcinoma patients. A family sample whose of their different behaviour with regard to the probands have been matched for gastric carci- occurrence of the combined form of atrophic noma patients by age, sex, occupation and gastritis.
Gastritis in Gastric Cunwr Relarives Table I. Composition of the materials
NO. of Mean age, M/F
Downloaded by [RMIT University Library] at 02:57 17 March 2016
Series
25
and their age-matched controls. Chi-square test was used in statistical calculations.
cases
years
Carcinoma probands
73
63
ratio 2.5
Grading of gastritis
Sibs of gastric carcinoma patients
127
59
0.7
Children of gastric carcinoma patients
159
37
0.8
Sihs of control probands
127
59
1.2
Children of control probands
159
37
1.0
Gastritis was graded and scored as follows: normal mucosa (score 0): no round cell infiltration, no loss of glands; slight, moderate and severe superficial gastritis (score l), slight, moderate and severe round infiltration but no loss of glands; slight, moderate and severe atrophic gastritis (scores 2, 3 and 4): slight, moderate and severe loss of glands ( 12- 15).
Cuntrols The controls comprise 452 first-degree relatives of 73 control probands computer matched by age, sex, occupation, and places of birth and residence for the gastric carcinoma patients. Controls represent a virtually symptomless (87%) over- 15-year-old population of South Finland. Because of the selection principles their age and sex distribution is similar to that of the series. The composition of the series and controls is described in detail elsewhere (9). The recovery rate was very high in both materials, about 90% of all living over-15-year-old relatives. The purpose of the study was explained to all participants and their verbal and written consent was obtained. Of the 452 control subjects we matched by age and sex the controls for the 127 sibs and IS9 children of gastric carcinoma patients. Histological methods
Endoscopy with direct vision gastric biopsy was performed in all subjects. About 4 specimens were taken from the antrum and 6 from the body, averaging 1 1.2 specimens per subject. The specimens were fixed in neutral buffered 10% formalin and embedded in paraffin. Haematoxylin-eosin and Alcian-blue (pH 2.5) -PAS stains were used. The status of the mucosa was evaluated by one of the authors without knowledge of the source of the specimens. Mathematical methods
Simple prevalences of topographically differcnt types of atrophic gastritis were calculated in sibs and children of gastric carcinoma probands
RESULTS The topographic distribution of gastritis in all series and controls is shown in Table 11. The main results are summarized in Table 111. It appears from Table I1 that sibs differ from their controls only with regard to the occurrence of combined AG. In addition, calculation of age-specific prevalences showed that this difference was present already in younger age-groups. On the other hand, the prevalence of AG affecting only the antral or only the body mucosa did not significantly differ from the controls. In children of carcinoma patients there was no enrichment of combined AG. On the contrary, the prevalence of combined AG was lower than in controls, although the difference was not statistically significant. A severe AG of the body was found in three children of the series but not in a single case in controls; neither was this difference statistically significant. Table 111 shows that even after age-matching the prevalence of combined AG was in sibs significantly higher than in children of gastric carcinoma patients. It should be noted, however, that the carcinoma probands of children and those of age-matched sibs had a different age distribution, the difference in mean age being about 22 years. On the other hand, the occurrence of combined AG in relatives of older carcinoma probands did not differ from that of the younger ones. Accordingly, the results of the comparison of the two generations of carcinoma
26 M . Kekki et nl. Table 11. Prevalences of topographically different types of atrophic gastritis (AG) AG affects hoth antruin and body
AG affects only body
AG affects only antrum
Total No. of cases
40* (31)'
20 (16)
34 (27)
127
19 (IS)'
17 (13)
34 (27)
127
Children of gastric carcinoma patients
4 (3)
10 ( 6 )
30 (19)
IS9
Children of control probands
10 (6)
9 (6)
24 (IS)
lS9
Scries Sibs of gastric carcinoma patients Sibs of control probands
Downloaded by [RMIT University Library] at 02:57 17 March 2016
*Number of cases 'Prevalence (%) 'The difference from sibs of gastric carcinoma patients is significant (p50.01)
Table 111. Prevalences of topographically different types of atrophic gastritis (AG) in age-matched children and sibs of gastric carcinoma patients Scries
Sibs of gastric carcinoma patients Children of gastric carcinoma patients
AG affects both antrum and body
AG affects only body
AG affects only antrum
Total No. of cases
10* (23)'
4 (9)
1s (34)
44
0 (0s
1 (2)
'j,
(21)
44
*Numbcr of cases 'Prevalence (%) 'Difference from sibs is highly significant (y~0.001)
families were hardly affected by the age differences of probands. Thc possible effect of sex and of histology of the tumour on the behaviour of sibs and children with regard to the occurrence of topographically different forms of AG was also studied. The calculations did not disclose significant differences. Thus the ratio of the prevalences of combined AG in males and females were 2.2 and 3.2, respectively, in the series and 2.5 and 2.6, respectively, in relatives of probands with intestinal and diffuse type of cancer. DISCUSSION The present study shows that there is an increased prevalence of combined atrophic gastritis (AG) in close relatives of patients with gastric carcinoma, when compared with agematched controls. However, the observed increase is solely due to enrichment of the combined AG in sibs of the gastric carcinoma
patients. No significant difference was seen between children of the series and those of the controls in this respect. Moreover, when sibs and children were age-matched with each other there was a highly significantly greater enrichment of combined AG in sibs. This finding shows that the difference between sibs and children is not due to differences in age. The explanation for the enrichment of the combined AG in sibs of gastric carcinoma patients is not obvious. Indeed, close relatives share not only a similar genetic background but also an in part similar environment. Correa (16) considers that this topographic type of gastritis is due to environmental influences and termed it "environmental" gastritis. In the present study, the children age-matched for the sibs of carcinoma probands might be considered to be living under largely similar environmental conditions as the sibs but they showed no enrichment of the combined AG, suggesting that genetic influences might be of some significance. On the other
Downloaded by [RMIT University Library] at 02:57 17 March 2016
Gastritis in Gastric Cancer Relatives
27
hand, the well known associations of Helico- risk of getting gastric carcinoma is increased in bacter pylori with the development of gastritis, close relatives of patients with this disease ( I 1). particularly at its early stages, strongly empha- Another important aspect to be considered is the sizes the importance of environmental factors. age factor. Indeed, already at a young age the However, according to preliminary data obtained sibs of gastric carcinoma patients show an from determinations of Helicobucter antibodies enrichment of combined AG, while in controls in the sera of sibs and children of carcinoma the combined AG is virtually absent in these probands the prevalence of antibody positivity age-groups. Because of the slow development did not significantly differ from that in their of malignancy from its prestages (22), the occurrence of a possible premalignant condition controls (17). Thus we believe that, in addition to environ- already at younger age might be as important a mental influences, genetic factors appear to finding as an overall increase of prevalences. participate in the development of combined AG and particularly in its accumulation in sibs of ACKNOWLEDGEMENTS gastric carcinoma patients. This study was supported by a grant from Yrjo The topographical subtypes of AG used in this study resemble those described by Strick- Jahnsson Foundation, Helsinki, Finland. land and Mackay (18) and Glass ( I ) as well as those delineated recently by the authors (12). Of REFERENCES these, phenotype B is possibly determined by I. Glass GBJ. The natural history of gastric atrophy: a one major recessive gene-pair (1 2,19) and review of immunologic aspects and possible links to phenotype A fits well with a dominant one (20). endogenous inhibitors of gastric secretion. Am J Dig Dis 1965, 10, 376-398 The present study as well as our earlier experience ( I 2) show that also the AB-type accumu- 2. C o m a P, Cuello C, Duque E. Carcinoma and intcstinal metaplasia of the stomach in Columbian migrants. J lates in the same families; however. the behaviNatl Cancer Inst 1970, 44, 297-306 our of the present combined AG is, because of 3. Heilmann K. Gastritis, intestinale Melapkdsie, Carzinom. its disappearance in the second generation, Thieme Verlag, Stuttgart, 1978 incompatible with a dominant mode of inherit- 4. Johansen A. Gastric carcinoma: a contribution to the pathology and to gastric cancer histogenesis. Departance. This leaves as further alternatives of a ment of Pathology, Bispebjaerg Hospital, Copenhagen, recessive autosomal or multigenetic model of 1981 inheritance. It seems that the nature of genetic 5 . Nagayo T, Komagoe T. Histological studies of gastric influences in the development of combined AG mucosal cancer with special reference to relationship of histological pictures between the mucosal cancer and remains an enigma, and limitations due to the the cancer-bearing gastric mucosa. Gann 1961, 5 2 , size and composition of the present series 109-119 preclude an appropriate genetic analysis. 6. Sipponen P, Kekki M, Siurala M. Atrophic gastritis and The high prevalence of combined AG in sibs intestinal metaplasia in gastric carcinoma. Comparison of gastric carcinoma patients might be, as with a representative population sample. Cancer 1983. 52. 1062-1068 suggested in the Chapter "Introduction", of some significance as a sign of an increased risk of 7. Stemmermann GN, Hayashi T. Intestinal metaplasia of the gastric mucosa: A gross and microscopic study of getting gastric carcinoma. The combined form its distribution in various disease states. J Ndtl Cancer of AG is a common "phenotype" of AG found Inst 1968, 41, 627-634 in patients with gastric carcinoma (21). Its close 8. Sipponen P, Kckki M, Haapakoski J, Ihamaki T, Siurala M. Gastric cancer risk in chronic atrophic gastritis: relations to gastric carcinoma have already been statistical calculations of cross-sectional data. In1 J stressed by Correa (2,115). In addition, our Cancer 1985, 35, 173-177 statistical calculations suggest that this form of 9. Ihamiiki T. Chronic atrophic gastritis in first-dcgree AG is associated with a high risk of contracting relatives of gastric carcinoma patients. Academic gastric carcinoma (8). Moreover, the present Dissertation, University of Helsinki, Yliopistopaino, Helsinki, 1987 results are in agreement with the finding that the
28 M. Krkki et al.
Downloaded by [RMIT University Library] at 02:57 17 March 2016
10. Kekki M, Ihamlki T, Saukkonen M, Varis K, Siurala M . Progression of gastritis at a population level. Comparison of a long-term follow-up with stochastic analysis of cross-sectional data. Scand J Gastroenterol
1980, 15, 651-655 I 1. Lehtola J. Family study of gastric carcinoma. Scand J Gastroenterol. 1978, 13, Suppl. S O 12. Kekki M, Siurala M, Vans K, Sipponen P, Sistoncn P, Nevanlinna RH. Classification principles and genetics of chronic gastritis. Scand J Gastrocnterol 1987, 22, Suppl. 141, 1-28 13. Rao SS, Krasner N, Thomson TJ. Chronic gastritis a simple classification. J Path01 1975, 117, 93-96 14. Schindler R. Gastritis. Grune & Stratton. New York, 1947 IS. Siurala M, Kivilaakso E, Sipponen P. Gastritis. In: Dcmling L, Domschke, cds. Klinische Gastroenterologie. Band I. Ceorg Thieme Verlag, Stuttgart, 1984. 321-337 16. Coma P. The etiology and pathogenesis of chronic gastritis. Three etiologic entities. Front Gastrointest Res
1980, 6, 98-108 17. Samloff MI. Valle J, Sipponen P, Kekki M, Siurala M. Unpublished data. 18. Strickland RG, Mackay IR. A reappraisal of the nature and significance of chronic atrophic gastritis. Dig Dis Sci 1973, 18, 426-440 19. Bonney GE, Elston RC, C o m a P, Haenszel W, Zavala DE, Zarama C, Collazos T, Cuello C. Genetic etiology of gastric carcinoma: 1. Chronic atrophic gastritis. Genet Epidcmiol 1986, 3, 213-224 20. Varis K, Samloff IM, Tiilikainen A, Ihamlki T, Kekki M, Sipponen P, Siurala M. Gastritis in first-degree relatives of pernicious anaemia, gastric cancer patients and controls. In: Rotter JI, Samloff IM, Riinoin DL. eds. The genetics and heterogenity of common gastrointestinal disorders. Academic Press, New York, 1980, 177-191 21. Siurala M, Sipponen P, Kekki M. Gastritis und Magenkarzinom. Leber Magen Darm 1984, 14, 139-148 22. Fujita S. Biology of early gastric carcinoma. Path Res Pract 1978, 163, 297-309
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Enrichment of Combined Antral and Corpus Atrophic Gastritis (“Combined AG”) in Sibs of Gastric Carcinoma Patients M. Kekki, M. Siurala & T. Ihamäki To cite this article: M. Kekki, M. Siurala & T. Ihamäki (1991) Enrichment of Combined Antral and Corpus Atrophic Gastritis (“Combined AG”) in Sibs of Gastric Carcinoma Patients, Scandinavian Journal of Gastroenterology, 26:sup186, 24-28, DOI: 10.3109/00365529109103983 To link to this article: http://dx.doi.org/10.3109/00365529109103983
Published online: 08 Jul 2009.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [RMIT University Library]
Date: 17 March 2016, At: 02:57
Enrichment of Combined Antral and Corpus Atrophic Gastritis ("Combined AG") in Sibs of Gastric Carcinoma Patients M. KEKKI, M. SIURALA, & T. IHAMAKI Second Dept. of Medicine, University of Helsinki, Helsinki, Finland
Downloaded by [RMIT University Library] at 02:57 17 March 2016
M. Kekki. M. Siurala, T. Ihamaki. Enrichment of combined antral and corpus atrophic gastritis ("combined AG") in sibs ofgastric carcinoma patients. Scand J Gastroenterol 1991,26(suppl 186), 24-28 The Occurrence of differcnt combinations of antral and corpus atrophic gastritis (AG) was studied in 127 sibs and IS9 children of 73 gastric carcinoma patients. Scventy-three control probands, age- and sex-matched for the carcinoma probands, and their 379 first-degree relatives were uscd as controls. Sibs of gastric carcinoma patients revealed a significant enrichment of AG affecting simultaneously both antrum and corpus (combined AG), while no such enrichment could be demonstrated in children, who behaved on the whole similarly to the controls. In addition, sibs of gastric carcinoma patients showed a significant aggregation of combined AG also when compared with children of similar age. This suggests that genetic factors in addition to environmental ones participate in the accumulation of combined AG in sihs. The lack of phenotype AB in children excludes the possibility of dominant Mendelian inheritance, hut leavcs the possibility of a recessive autosomal or multigenetic inheritance. The enrichment of combined AG in sibs of gastric carcinoma patients could be one of the factors involved in the increased liability of close relatives of gastric carcinoma patients to contract gastric malignancy.
K q words: Gastritis; family study; gastric cancer relativcs Matti Kekki. M.D.,Second Dept. of Medicine, Universitv of Helsinki. SF-OOZY0 Helsinki, Finland
Atrophic gastritis (AG) affecting simulta- places of birth and residence, are used as neously antrum and body ("combined AG", controls. called by Glass AB-gastritis; 1) is commonly found in patients with gastric carcinoma (2-7) MATERIAL AND METHODS and seems to carry an increased risk of underlying malignancy. According to our recent calcu- Series The series consists of 301 first-degree relatives lations (8) the risk of getting gastric carcinoma is significantly increased in the final stages of of 73 consecutive and histologically verified atrophic gastritis, particularly those of antral cases of gastric carcinoma diagnosed at the mucosa. In the combined forms of AG the risk Gastroenterological Unit, Second Department of is presumably still higher: it represents the Medicine, University of Helsinki, Helsinki, multiplicand of risks due to antral and body AG Finland. Of the 30 1 relatives adequate biopsies (8). For this reason one could anticipate an were available from 286 subjects of whom 127 enrichment of this form of AG in different risk were sibs and 159 were children of the index conditions of gastric carcinoma, such as close patients. The composition of the series and relatives of patients with this disease (9-1 I). The controls and their mean age and sex distribution present paper deals with the occurrence of are given in Table 1. Sibs and children have been combined AG in sibs and children of gastric treated separately throughout the study because carcinoma patients. A family sample whose of their different behaviour with regard to the probands have been matched for gastric carci- occurrence of the combined form of atrophic noma patients by age, sex, occupation and gastritis.
Gastritis in Gastric Cunwr Relarives Table I. Composition of the materials
NO. of Mean age, M/F
Downloaded by [RMIT University Library] at 02:57 17 March 2016
Series
25
and their age-matched controls. Chi-square test was used in statistical calculations.
cases
years
Carcinoma probands
73
63
ratio 2.5
Grading of gastritis
Sibs of gastric carcinoma patients
127
59
0.7
Children of gastric carcinoma patients
159
37
0.8
Sihs of control probands
127
59
1.2
Children of control probands
159
37
1.0
Gastritis was graded and scored as follows: normal mucosa (score 0): no round cell infiltration, no loss of glands; slight, moderate and severe superficial gastritis (score l), slight, moderate and severe round infiltration but no loss of glands; slight, moderate and severe atrophic gastritis (scores 2, 3 and 4): slight, moderate and severe loss of glands ( 12- 15).
Cuntrols The controls comprise 452 first-degree relatives of 73 control probands computer matched by age, sex, occupation, and places of birth and residence for the gastric carcinoma patients. Controls represent a virtually symptomless (87%) over- 15-year-old population of South Finland. Because of the selection principles their age and sex distribution is similar to that of the series. The composition of the series and controls is described in detail elsewhere (9). The recovery rate was very high in both materials, about 90% of all living over-15-year-old relatives. The purpose of the study was explained to all participants and their verbal and written consent was obtained. Of the 452 control subjects we matched by age and sex the controls for the 127 sibs and IS9 children of gastric carcinoma patients. Histological methods
Endoscopy with direct vision gastric biopsy was performed in all subjects. About 4 specimens were taken from the antrum and 6 from the body, averaging 1 1.2 specimens per subject. The specimens were fixed in neutral buffered 10% formalin and embedded in paraffin. Haematoxylin-eosin and Alcian-blue (pH 2.5) -PAS stains were used. The status of the mucosa was evaluated by one of the authors without knowledge of the source of the specimens. Mathematical methods
Simple prevalences of topographically differcnt types of atrophic gastritis were calculated in sibs and children of gastric carcinoma probands
RESULTS The topographic distribution of gastritis in all series and controls is shown in Table 11. The main results are summarized in Table 111. It appears from Table I1 that sibs differ from their controls only with regard to the occurrence of combined AG. In addition, calculation of age-specific prevalences showed that this difference was present already in younger age-groups. On the other hand, the prevalence of AG affecting only the antral or only the body mucosa did not significantly differ from the controls. In children of carcinoma patients there was no enrichment of combined AG. On the contrary, the prevalence of combined AG was lower than in controls, although the difference was not statistically significant. A severe AG of the body was found in three children of the series but not in a single case in controls; neither was this difference statistically significant. Table 111 shows that even after age-matching the prevalence of combined AG was in sibs significantly higher than in children of gastric carcinoma patients. It should be noted, however, that the carcinoma probands of children and those of age-matched sibs had a different age distribution, the difference in mean age being about 22 years. On the other hand, the occurrence of combined AG in relatives of older carcinoma probands did not differ from that of the younger ones. Accordingly, the results of the comparison of the two generations of carcinoma
26 M . Kekki et nl. Table 11. Prevalences of topographically different types of atrophic gastritis (AG) AG affects hoth antruin and body
AG affects only body
AG affects only antrum
Total No. of cases
40* (31)'
20 (16)
34 (27)
127
19 (IS)'
17 (13)
34 (27)
127
Children of gastric carcinoma patients
4 (3)
10 ( 6 )
30 (19)
IS9
Children of control probands
10 (6)
9 (6)
24 (IS)
lS9
Scries Sibs of gastric carcinoma patients Sibs of control probands
Downloaded by [RMIT University Library] at 02:57 17 March 2016
*Number of cases 'Prevalence (%) 'The difference from sibs of gastric carcinoma patients is significant (p50.01)
Table 111. Prevalences of topographically different types of atrophic gastritis (AG) in age-matched children and sibs of gastric carcinoma patients Scries
Sibs of gastric carcinoma patients Children of gastric carcinoma patients
AG affects both antrum and body
AG affects only body
AG affects only antrum
Total No. of cases
10* (23)'
4 (9)
1s (34)
44
0 (0s
1 (2)
'j,
(21)
44
*Numbcr of cases 'Prevalence (%) 'Difference from sibs is highly significant (y~0.001)
families were hardly affected by the age differences of probands. Thc possible effect of sex and of histology of the tumour on the behaviour of sibs and children with regard to the occurrence of topographically different forms of AG was also studied. The calculations did not disclose significant differences. Thus the ratio of the prevalences of combined AG in males and females were 2.2 and 3.2, respectively, in the series and 2.5 and 2.6, respectively, in relatives of probands with intestinal and diffuse type of cancer. DISCUSSION The present study shows that there is an increased prevalence of combined atrophic gastritis (AG) in close relatives of patients with gastric carcinoma, when compared with agematched controls. However, the observed increase is solely due to enrichment of the combined AG in sibs of the gastric carcinoma
patients. No significant difference was seen between children of the series and those of the controls in this respect. Moreover, when sibs and children were age-matched with each other there was a highly significantly greater enrichment of combined AG in sibs. This finding shows that the difference between sibs and children is not due to differences in age. The explanation for the enrichment of the combined AG in sibs of gastric carcinoma patients is not obvious. Indeed, close relatives share not only a similar genetic background but also an in part similar environment. Correa (16) considers that this topographic type of gastritis is due to environmental influences and termed it "environmental" gastritis. In the present study, the children age-matched for the sibs of carcinoma probands might be considered to be living under largely similar environmental conditions as the sibs but they showed no enrichment of the combined AG, suggesting that genetic influences might be of some significance. On the other
Downloaded by [RMIT University Library] at 02:57 17 March 2016
Gastritis in Gastric Cancer Relatives
27
hand, the well known associations of Helico- risk of getting gastric carcinoma is increased in bacter pylori with the development of gastritis, close relatives of patients with this disease ( I 1). particularly at its early stages, strongly empha- Another important aspect to be considered is the sizes the importance of environmental factors. age factor. Indeed, already at a young age the However, according to preliminary data obtained sibs of gastric carcinoma patients show an from determinations of Helicobucter antibodies enrichment of combined AG, while in controls in the sera of sibs and children of carcinoma the combined AG is virtually absent in these probands the prevalence of antibody positivity age-groups. Because of the slow development did not significantly differ from that in their of malignancy from its prestages (22), the occurrence of a possible premalignant condition controls (17). Thus we believe that, in addition to environ- already at younger age might be as important a mental influences, genetic factors appear to finding as an overall increase of prevalences. participate in the development of combined AG and particularly in its accumulation in sibs of ACKNOWLEDGEMENTS gastric carcinoma patients. This study was supported by a grant from Yrjo The topographical subtypes of AG used in this study resemble those described by Strick- Jahnsson Foundation, Helsinki, Finland. land and Mackay (18) and Glass ( I ) as well as those delineated recently by the authors (12). Of REFERENCES these, phenotype B is possibly determined by I. Glass GBJ. The natural history of gastric atrophy: a one major recessive gene-pair (1 2,19) and review of immunologic aspects and possible links to phenotype A fits well with a dominant one (20). endogenous inhibitors of gastric secretion. Am J Dig Dis 1965, 10, 376-398 The present study as well as our earlier experience ( I 2) show that also the AB-type accumu- 2. C o m a P, Cuello C, Duque E. Carcinoma and intcstinal metaplasia of the stomach in Columbian migrants. J lates in the same families; however. the behaviNatl Cancer Inst 1970, 44, 297-306 our of the present combined AG is, because of 3. Heilmann K. Gastritis, intestinale Melapkdsie, Carzinom. its disappearance in the second generation, Thieme Verlag, Stuttgart, 1978 incompatible with a dominant mode of inherit- 4. Johansen A. Gastric carcinoma: a contribution to the pathology and to gastric cancer histogenesis. Departance. This leaves as further alternatives of a ment of Pathology, Bispebjaerg Hospital, Copenhagen, recessive autosomal or multigenetic model of 1981 inheritance. It seems that the nature of genetic 5 . Nagayo T, Komagoe T. Histological studies of gastric influences in the development of combined AG mucosal cancer with special reference to relationship of histological pictures between the mucosal cancer and remains an enigma, and limitations due to the the cancer-bearing gastric mucosa. Gann 1961, 5 2 , size and composition of the present series 109-119 preclude an appropriate genetic analysis. 6. Sipponen P, Kekki M, Siurala M. Atrophic gastritis and The high prevalence of combined AG in sibs intestinal metaplasia in gastric carcinoma. Comparison of gastric carcinoma patients might be, as with a representative population sample. Cancer 1983. 52. 1062-1068 suggested in the Chapter "Introduction", of some significance as a sign of an increased risk of 7. Stemmermann GN, Hayashi T. Intestinal metaplasia of the gastric mucosa: A gross and microscopic study of getting gastric carcinoma. The combined form its distribution in various disease states. J Ndtl Cancer of AG is a common "phenotype" of AG found Inst 1968, 41, 627-634 in patients with gastric carcinoma (21). Its close 8. Sipponen P, Kckki M, Haapakoski J, Ihamaki T, Siurala M. Gastric cancer risk in chronic atrophic gastritis: relations to gastric carcinoma have already been statistical calculations of cross-sectional data. In1 J stressed by Correa (2,115). In addition, our Cancer 1985, 35, 173-177 statistical calculations suggest that this form of 9. Ihamiiki T. Chronic atrophic gastritis in first-dcgree AG is associated with a high risk of contracting relatives of gastric carcinoma patients. Academic gastric carcinoma (8). Moreover, the present Dissertation, University of Helsinki, Yliopistopaino, Helsinki, 1987 results are in agreement with the finding that the
28 M. Krkki et al.
Downloaded by [RMIT University Library] at 02:57 17 March 2016
10. Kekki M, Ihamlki T, Saukkonen M, Varis K, Siurala M . Progression of gastritis at a population level. Comparison of a long-term follow-up with stochastic analysis of cross-sectional data. Scand J Gastroenterol
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