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Background: Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized., Objective: To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers., Design, Setting, and Participants: In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis., Results: In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2-ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549-BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden., Conclusions: Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: The majority of clinical prostate cancers are multifocal with morphological and molecular heterogeneity. Adequate tissue representation is crucial for the clinical utility of multigene panel sequencing of core needle biopsies. The aim of this study was to evaluate the genomic heterogeneity in multifocal prostate cancer and to analyze how representative preoperative biopsies are of spatially separated tumor foci., Methods: We analyzed at least 2 tumor foci and 1 to 3 preoperative biopsy cores from 11 patients. Diagnostic biopsies, as well as fresh frozen and formalin-fixed paraffin-embedded samples, from major tumor foci of radical prostatectomy specimens were macrodissected for the enrichment of tumor tissue. DNA was extracted and sequenced. We analyzed structural alterations, mutations, and copy number variations and compared the genomic profiles of tumor foci with those of preoperative biopsies., Results: Alterations were rarely shared between foci, indicating a high degree of genomic heterogeneity. In 8 of 11 men at least 1 tumor focus was represented by the biopsies defined as harboring at least 1 common clonal somatic event. In only one case, somatic alterations from two spatially separate tumors were identified in the biopsies. Of the mutations and structural variants detected in fresh frozen or formalin-fixed paraffin-embedded prostatectomy material, only an average of 19% (range 0-44) and 55% (range 0-100), respectively, were found in preoperative biopsies where a common somatic origin was established., Conclusions: Multifocal prostate cancer is a somatically heterogeneous disease in which systematic needle biopsies do not provide sufficient molecular representation of the somatic alterations detected in spatially distinct tumor areas. Targeted biopsies, directed at separate tumor foci, could potentially improve tissue representation of these heterogeneous foci in preoperative biopsies., (© 2019 Wiley Periodicals, Inc.)

While tobacco and alcohol are established risk factors for oesophageal squamous-cell carcinoma, their roles in the aetiology of the increasingly common oesophageal adenocarcinoma remains uncertain. We tested the association between tobacco, snuff and alcohol use and the risk of oesophageal and cardia cancer in a nationwide, population-based case-control study in Sweden. Face-to-face interviews were conducted with 618 (81% of all eligible) patients (189 oesophageal adenocarcinoma, 262 cardia adenocarcinoma and 167 oesophageal squamous-cell carcinoma) and 820 control subjects. Odds ratios (OR) were calculated by logistic regression with multivariate adjustments for potential confounding. The risk of oesophageal adenocarcinoma was not associated with snuff or alcohol use, and the association with smoking was weak or absent. Gastric cardia adenocarcinoma was dose-dependently associated with smoking (OR=4.2, 95% CI=2.5-7.0 among heavy smokers compared with never-smokers), but not with alcohol or snuff use. Oesophageal squamous-cell carcinoma was strongly associated with tobacco, moderately with alcohol, but not with snuff use; combined use of tobacco and alcohol entailed a strongly increased risk (OR=23.1, 95% CI=9.6-56.0 among heavy users compared with never-users). We conclude that tobacco smoking, a strong risk factor for oesophageal squamous-cell carcinoma and cardia adenocarcinoma, does not play an important role in the aetiology of oesophageal adenocarcinoma. None of the studied exposures can explain the increasing incidence of oesophageal adenocarcinoma.

Few studies have provided information on the role of smoking and alcohol in the carcinogenesis of gastric cancer by sub-site and histologic type. The relationship of snuff dipping with risk of gastric cancer has also been rarely studied. In a population-based case-control study conducted in 5 counties of Sweden from February 1989 to January 1995, a total of 90 cases of gastric cardia cancer, 260 and 164 cases of distal gastric cancer of intestinal and diffuse types, respectively, and 1164 frequency-matched control subjects were personally interviewed about life-time smoking, use of smokeless tobacco and use of alcohol 20 years ago. Current smokers had a higher risk than never-smokers for all 3 kinds of gastric adenocarcinoma [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.0-3.1 for gastric cardia adenocarcinoma; OR 1.8, 95% CI 1.2-2.7 for distal gastric cancer of intestinal type; and OR 2.2, 95% CI 1.4-3.5 for distal gastric cancer of diffuse type], and the risk rose with increasing dose and duration of smoking among current smokers. However, no elevated risk was observed for ex-smokers. Neither intake of alcoholic beverages nor snuff dipping was associated with an increased risk of any type of cardia or gastric cancer. Our study did not support the hypothesis that the role of tobacco differs by sub-site and histologic sub-type of gastric cancer., (Copyright 1999 Wiley-Liss, Inc.)

While use of hormone-replacement therapy (HRT) effectively alleviates menopausal symptoms and prevents osteoporosis and possibly cardiovascular disease, there is concern of a detrimental impact on breast-cancer risk. There is a particular lack of data regarding the effect of long-term use of oestrogen-progestin combinations on breast-cancer risk. We conducted a large epidemiological study in Sweden, where combined oestrogen-progestin treatment has been predominant, to examine the influence of different regimens of menopausal hormone therapy on breast-cancer risk. In this population-based case-control study, 3,345 women aged 50 to 74 years with invasive breast cancer (84% of all eligible) and 3,454 controls of similar age (82% of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on use of hormone replacement and on potential confounding factors. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multiple logistic regression. There was a trend of increasing breast-cancer risk with duration of oestrogen/oestrogen-progestin use (OR for women treated at least 10 years, 2.43; 95% CI, 1.79-3.30, as compared to never-users), with statistically significant estimates only for women with BMI<27 kg/m2. Excess risks were observed to current use and use that ceased more than 10 years ago (OR for women treated at least 5 years, OR was 2.68, 95% CI, 2.09-3.42, and OR 2.57, 95% CI, 1.28-5.15, as compared with never-users, respectively). A positive association which was noted for use of oestrogen combined with testosterone-derived progestins appeared especially pronounced with continuously combined regimens. Long-term use of replacement oestrogens with or without progestins may substantially increase the incidence of post-menopausal breast cancer, particularly among non-obese women.

It is unclear whether age at menarche is causally involved in breast-cancer aetiology, or serves a correlate of other early-life exposures. Other aspects of reproductive life, including cycle length and regularity, climacteric symptoms, reproductive history and oral contraceptive use, are also incompletely investigated. We examined these issues in a population-based case-control study, including 3,016 women aged 50 to 74 years with invasive breast cancer, and 3,263 controls of similar age. Mailed questionnaires and telephone interviews were used to collect information on menstrual and reproductive characteristics as well as use of oral contraceptives. We found a statistically significant negative association between increasing age at menarche and breast-cancer risk in women born before 1925 but not after. Length of the menstrual cycle at age 30 seemed to be adversely related to breast-cancer risk, with OR for women with cycle lengths < 24 days and > 30 days being 0.76 and 1.18, as compared with women with a cycle length of 28 days. There was a strong trend of decreasing breast-cancer risk with increasing parity (OR per borne child 0.85, 95% CI 0.80-0.90). Lactation, menopausal symptoms or past use of oral contraceptives did not appear associated with breast-cancer risk. Our findings provide some evidence of a role of environmental correlates of early menarche in breast-cancer aetiology, and underline the importance of childbirth, especially early in life, in the prevention of breast cancer. Our data are not readily compatible with an important influence of former oral contraceptive use on post-menopausal breast-cancer risk.

Notwithstanding its biologic plausibility, the association between physical activity and endometrial cancer has been analyzed in only a few epidemiological studies. Retrospective assessment of exposure and small sample size often hampers interpretation of published data. We studied risk for endometrial cancer in relation to physical activity at work in a large cohort of Swedish women identified in the nationwide censuses in 1960 and 1970, with jobs that could be consistently classified into one of 4 levels of physical demands. Follow-up from 1971 through 1989 was accomplished through record linkages. Multivariate Poisson regression models were used to estimate relative risk. The risk for endometrial cancer increased regularly with decreasing level of occupational physical activity (p for trend < 0.001), and was associated more strongly with activity in 1970 than in 1960. In multivariate analyses, adjusted for age at follow-up, place of residence, calendar year of follow-up, and social class, the relative risk among women with the same physical activity level in 1960 and in 1970 was 30% higher for sedentary as compared with high/very high activity level; (p for trend=0.04). The protective effect of physical activity appeared to be confined to women aged 50 to 69, among whom sedentary work was associated with a 60% higher risk than that observed among women estimated to be physically most active. The excess seemed to disappear within 10 years after a change in physical activity level. Although confounding cannot be ruled out in our data, occupational physical activity appears to reduce the risk for endometrial cancer.

Adult obesity has been associated with an increased risk of post-menopausal breast cancer, but it is unclear whether this relationship reflects a causal role of obesity during childhood and adolescence, of weight gain during adult life or of adult obesity per se. In a population-based case-control study in all of Sweden, we included 3,345 (84% of all eligible) women aged 50-74 years with invasive breast cancer, and 3,454 (82% of all selected) controls of similar age. Mailed questionnaires and telephone interviews were used to collect detailed information on anthropometric measures. Odds ratios were estimated through multiple logistic regression. Women with the leanest somatotype at age 7 had about a 3-fold higher risk of breast cancer than the most obese (P for trend 0.0009). A suggested protective effect of a high body mass at age 18 and a detrimental influence of body mass 1 year prior to data collection largely reflected the effect of weight gain after age 18, a strong predictor of breast cancer risk. Among women at least 20 years post menopause, those who had gained 30 kg or more since age 18 had an odds ratio of 2.04 (95% confidence interval 1.20-3.48) of breast cancer compared with those who had maintained their weight unchanged. The effect of weight gain was unequivocal among non-users but not among users of hormone replacement therapy. Our findings have important implications, suggesting weight preservation as a means for prevention of post-menopausal breast cancer as well as a causal role of childhood body build in breast cancer etiology.

Huge differences in incidence rates of invasive cervical cancer occur among populations. These differences reflect the influences of both etiological environmental factors and removal of precursor lesions detected upon screening. The purposes of this article are (i) to describe similarities and differences in the shapes and magnitudes of age-specific incidence rates of invasive cervical cancer before screening had an effect, (ii) to provide baseline data for further global study of screening effects, and (iii) to provide baseline incidence data for the design of optimal screening programs. To eliminate the impact of screening effects, we have selected age-specific incidence rates from times when and from populations in which screening was insignificant. The selected rates were suitably scaled and compared regarding age at onset of increase in incidence, age at peak incidence, and rate of subsequent decline. Despite a 16-fold difference in incidence rates, all curves had the same basic structure, with an increase to a peak followed by a decline or a plateau. Although all populations but one had an onset around age 25, 7 European countries showed an earlier peak age (mean = 46 vs. 59) and a more rapid decline after the peak than most other populations. The common basic shape of the age-specific incidence curve, overall, suggests a relatively similar development of invasive cervical cancer in different populations. These results illustrate the underlying similarities in the markedly different age-specific incidence rates of invasive cervical cancer. They also provide a basis for studying screening effects and for optimizing screening programs in specific geographic areas.

The role of diet in the etiology of prostate cancer remains unclear, because results from several case-control and cohort studies on fat intake and risk of prostate cancer have been inconsistent; few of the studies have adjusted the results for caloric intake. To examine the relationship between energy, intake of several nutrients and risk of prostate cancer (all stages combined and advanced stages separately), we conducted a population-based case-control study in Orebro County, Sweden, from 1989 through 1994. A total of 526 patients with newly diagnosed prostate cancer and 536 controls, randomly selected from the population register and frequency-matched by age, were included in the analyses. Information about dietary intake was obtained from a self-administered semi-quantitative food frequency questionnaire. Odds ratios with 95% confidence intervals were estimated by unconditional logistic regression. In age-adjusted analyses, there were positive associations of prostate cancer (all stages combined) risk with total energy intake as well as intake of total fat (saturated and monounsaturated), protein, retinol and zinc. The positive association with energy intake was stronger for advanced cancer, with an excess risk of 70% for the highest quartile vs. the lowest. After adjustment for energy intake, there was no apparent association of prostate cancers (all stages combined) with any of the investigated nutrients. However, a weak positive association between intake of retinol and advanced cancer was observed. We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer.

We evaluated the hypothesis that smoking increases the incidence of and mortality from prostate cancer. High-quality smoking information was collected in 1971-1975 in a nation-wide cohort of 135,006 male construction workers in Sweden. We achieved virtually complete follow-up through record linkages and ascertained as of December 1991 2,368 incident cases of prostate cancer and 709 deaths due to this disease. Rate ratios (RR) of prostate cancer incidence and mortality, with 95% confidence intervals (CI), were estimated in Poisson-based age-adjusted models, with amount and duration of smoking as independent variables. We found no convincing association between current smoking status, number of cigarettes smoked or years since onset and risk of prostatic cancer. The age-adjusted incidence RR among previous smokers was 1.09 and among current smokers 1.11 compared with non-smokers. Weak and inconsistent trends were seen with increasing number of cigarettes smoked per day and increasing duration among current smokers. Smokers of 15 or more cigarettes daily for at least 30 years experienced an incidence RR of 1.30. Mortality in ex-smokers was similar to that in never-smokers; it was, however, slightly increased among current smokers without any trend with amount smoked or duration. The weak and inconsistent associations between smoking and prostate cancer could easily have arisen due to bias or confounding. We therefore conclude that smoking is most likely not causally linked to the occurrence of prostate cancer.

Trends in the incidence of non-epithelial cancers are particularly likely to reflect environmental carcinogens, since these malignancies are not commonly the targets of screening efforts, and have generally not been closely associated with life style factors such as cigarette smoking and diet. We used data from nation-wide cancer registries in Denmark, Finland, and Sweden to examine trends in non-epithelial cancers over the period 1961-1990. Linear regression analysis of age-standardized rates, and age-period-cohort models were fit to assess the temporal patterns within each country. Within each of the 3 countries, there was a similarly increasing incidence of both hematological malignancies and nervous system/bone/soft-tissue neoplasms. The increases were smallest in children and adolescents (ages 0-14), moderate among young and middle aged adults (ages 15-64), and most pronounced among the elderly (ages 65+). Age-period-cohort modeling suggested that the dominant factor in the increases were birth cohort effects. It is not clear what factors underlie this increase in incidence; it seems most likely that increases both in diagnostic efficiency and in exposure to environmental carcinogens play a role.

We determined risk factors for late deaths from cutaneous malignant melanoma (CMM) based on clinical characteristics at diagnosis, initial surgical treatment, histopathologic features of the primary tumor and type of eventual recurrences during follow-up. We examined deaths from CMM 8 or more completed years after the initial diagnosis in a case-control study nested in a nationwide cohort comprising all 8,838 patients with CMM diagnosed in Sweden during 1960-1978 with complete follow-up through 1986. There were 285 case patients and 285 control patients, individually matched by sex, age and follow-up time. Conditional logistic regression was used to obtain odds ratios (OR) as estimates of the relative risk. The risk of late mortality increased stepwise, almost 19-fold, with increasing tumor thickness from < or = 0.75 to > or = 7.00 mm. Besides the thickest tumors (> or = 7.00 mm), those of intermediate thickness (1.50-2.49 mm) had the highest risk (OR 8.5). After adjustment for tumor thickness, non-radical primary surgical treatment increased the risk of late mortality almost 3-fold while prophylactic lymph node dissection entailed a significantly reduced risk of late mortality (OR 0.5); the histopathologic features increasing level of invasion and vertical growth phase also remained significantly associated with a poor outcome. In a multivariate model, non-radical primary surgical treatment, prophylactic lymph node dissection, vertical growth phase, level of invasion and lymphocyte reaction were independent predictors of late mortality.

Cytologic screening for cervical cancer has proven to be beneficial in many countries, although the value of this intervention in women older than 50 years remains controversial. The purpose of this study was to investigate the efficiency of detecting cancer in situ by means of a cytologic smear at different ages, with special emphasis on the benefit of screening in women above the age of 50. We analyzed 466,275 smears taken in an open cohort of 118,890 women in Sweden between 1969 and 1988. The number of cancers in situ detected per 1,000 smears, the detection ratio, was used as an outcome measure in univariate analyses and in multivariate regression models. Cancer in situ was detected in 1,076 women in the study cohort. The detection ratio peaked at ages 30 to 34 and decreased heavily during the next 15 years of age. The efficiency of taking smears at ages above 50 was only 20 per cent (OR, 0.19; 95% CI, 0.14-0.26) of that at ages 30 to 34. These results were not changed when adjusting for time period and time interval since the previous smear. In spite of a high incidence of invasive cervical cancer in older women, the benefit of cytologic screening to detect cancer in situ above the age of 50 is uncertain.

Although numerous studies have identified obesity or high relative weight as a risk factor for renal-cell cancer in women, the degree to which this effect is present in men remains unclear. A multicenter population-based case-control study concerning incident cases of histologically verified renal-cell cancer (n = 1,732) and age- and sex-matched controls (n = 2,309) was conducted in Australia, Denmark, Germany (2 centers), Sweden and the United States. Relative weight was estimated by the body mass index, and the association between this factor and other factors, such as height, physical activity and use of amphetamines, was measured by the relative risk estimated in logistic regression models. Body mass index was found to be a risk factor among women and, to a lesser extent, among men. A 3-fold increased risk (RR = 3.6, 95% CI = 2.3-5.7) was observed for women with a relative weight in the top 5% compared with those in the lowest quartile. Rate of weight change (estimated as weight change per annum in kilograms) appeared to be an independent risk factor among women but not among men. Physical activity and height were unrelated to risk of renal-cell cancer regardless of level of BMI, while use of amphetamines was associated with an increased risk among men, although no dose or duration effect was seen. Our findings verify the link between high relative weight and risk of renal-cell cancer, particularly among women. The mechanism that underlies this association is, however, still unclear, although the rate of weight change may play a role.

The incidence of testicular cancer was examined in the Nordic and Baltic countries, Poland and Germany by collaboration among 10 cancer registries. Population-based registers were used to analyze a total of 34,309 cases, diagnosed from the start of registration (varying from 1943 in Denmark to 1980 in Latvia and Lithuania) through 1989. An approximately 10-fold geographical variation was found in 1980, with the highest age-standardized incidence rate (7.8 per 10(5); world standard population) in Denmark and the lowest (0.9) in Lithuania. During the entire period of registration, incidence increased rapidly in all countries, by 2.3 to 3.4 per cent annually in the Nordic countries and by about 5 per cent in Poland and Germany; there was some evidence of a slower increase in Denmark and Poland after 1975. The rising trend was more pronounced for ages below 30. The age-specific incidence peaked in all countries at ages 25 to 34, but the geographical variation was considerable. Our data indicate that environmental influences on testicular cancer are strong. Exposure to causal factors mostly takes place early in life, shows substantial geographical variation, and increases over time, so that the age-standardized incidence doubles every 15 to 25 years. New aetiological hypotheses are needed to accommodate these salient features of the descriptive epidemiology, since risk factors considered so far cannot explain the observed pattern.

A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1%) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and beta-carotene had an unequivocal protective effect, but alpha-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and beta-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant.

Exposures early in life seem to play an important role in the development of gastric cancer, but their nature is not well understood. In a population-based case-control study, we examined weight, height and body-mass index (BMI) at the age of 20 as well as indices of socioeconomic conditions. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric cancer patients and 679 of 880 eligible control subjects, sampled from population registers and frequency matched by age and gender. Gastric cancer risk was negatively associated with height. Risk was positively, associated with weight at age 20 in both sexes. The highest BMI-quartile was associated with an increased risk. This association between BMI and risk was confined to BMI at age 20, and disappeared for BMI 20 years prior to interview. High socioeconomic status (SES) as well as long education carried a decreased risk of gastric cancer. Number of siblings was positively associated with risk. Factors related to short stature and high adolescent body weight are associated with an increased risk of gastric cancer, as is a high number of siblings. These factors may reflect influences of dietary patterns early in life.

A hospital-based case-control study of oesophageal cancer was carried out in the Heilongjiang Province, a low-risk area for oesophageal cancer in China. From May 1985 to May 1989, 196 histologically confirmed cases and 392 controls with other (non-neoplastic) diseases were personally interviewed in the wards of 5 major hospitals. Information was obtained about usual consumption in the early 1980s of 32 major contributors to the diet in the province, socio-demographic status, smoking and alcohol consumption. Odds ratios (OR) were obtained from logistic regression models, and confounding was controlled by means of multivariate models. Smoking and alcohol consumption were major risk factors for oesophageal cancer in this population. Smokers of handmade cigarettes exhibited a particularly high risk. A near multiplicative synergism was found between smoking and alcohol consumption. There was a significant inverse dose-risk trend for combined consumption of vegetables and fruits; a 300-g increase per day lowered risk by 35%. Vitamin C intake was negatively associated with risk; a 100-mg increase per day lowered risk by 39%. Our data suggest a modifying effect of vitamin C and beta-carotene on risk associated with smoking, but the power of analyses was low. Salt, salt-preserved foods and pickled vegetables were not associated with increased risk. High temperature of meals and drinks was a strong risk indicator in this population. The strength of tea and overall tea consumption were independent determinants of the risk.

Previous studies have provided conflicting information on the role of tobacco and alcohol in gastric carcinogenesis. A population-based case-control study with 338 histologically confirmed gastric-cancer cases and 679 control subjects was conducted. Information relating to life-time tobacco consumption, alcohol intake and diet during adolescence and 20 years before interview, and to socio-economic conditions was obtained through face-to-face interviews. Current cigarette smokers were found to have a greater risk than non-users of tobacco. The duration of cigarette or pipe smoking was positively associated with gastric-cancer risk. There was significant interaction between tobacco use and fruit consumption. High fruit intake was more protective among users of tobacco than among non-users, and the risk estimates associated with cigarette smoking were higher among those with low fruit consumption than among frequent fruit-eaters. Likewise, though to a lesser extent, vegetable intake interacted with tobacco use. Snuff dipping and alcohol intake was not associated with gastric-cancer risk. However, high alcohol intake tended to increase the risk associated with tobacco use. This study adds further support to the role of tobacco smoking in gastric carcinogenesis, and demonstrates that high intake of fruits and vegetables may be particularly beneficial in smokers.

A case-control study to evaluate risk factors of gastric cancer was carried out in areas with contrasting incidence rates in Sweden. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric-cancer cases and 669 of 880 eligible control subjects, sampled from population registers and frequency-matched by age and gender. We focused on 2 periods, adolescence and 20 years prior to interview. The association of gastric-cancer risk with dietary habits during adolescence were similar to that found for the period 20 years before interview; high consumption of wholemeal bread, fruit and vegetables was associated with reduced gastric-cancer risk. In addition, cheese, fish and tea had a protective effect during adolescence. Increased gastric-cancer risk was related to whole-milk consumption, but this association decreased substantially in a multivariate analysis including vegetables. There was a positive relationship between gastric-cancer risk and the age at which the interviewees started using refrigerators. This population-based study confirmed the protective effect of a high consumption of vegetables and fruit in the development of gastric cancer, but failed to find any association between intake of meat, sausage, cold cuts, liver, salt, coffee, the habit of frying, smoking or grilling foods, and risk of gastric cancer.

Trends in the incidence of stomach cancer among 52,604 patients notified to the National Swedish Cancer Registry in 1960 through 1984 were analysed. Age-standardized incidence rates declined throughout the period, from 47.1 to 24.6 per 10(5) in males and from 23.8 to 12.7 per 10(5) in females. Among males the decline in incidence was more pronounced in younger age strata, 35-54 years, while in females it reached a maximum at ages 70-74 years. In a multivariate analysis the age-cohort model adequately represented the data and there was no reason to separate the effects of the full age-period-cohort model. Compared with the cohort born in 1876-1884, the relative risk of developing stomach cancer was 0.46 (95% CI:0.44-0.48) in males and 0.39 (95% CI:0.37-0.42) in females born in 1906-1914. This supports the view that the declining incidence is due to a change in the exposure of the population to aetiological factors of stomach cancer and not to refinement of the diagnosis and classification of abdominal tumours. The results also imply that exposure to aetiological factors early in life together with a long induction period is of importance in the development of stomach cancer.