Recent trends in cancer mortality in the UK.

Comparisons of survival rates of given diseases with different treatments or in different places often gave misleading results until the introduction of controlled trials. Recent reports of relatively low survival rates following the treatment of cancer in the UK compared to the rates in other countries, not based on controlled trials, may consequently be misleading. Their validity has, therefore, been tested by comparing the levels and trends in mortality--the ultimate criterion by which the success or failure of any system of care can be judged. For this purpose, rates and trends in rates over 20-50 years have been compared in five European countries of similar economic status (France, Italy, the Netherlands, Sweden, and the UK). The UK rates are not generally worse than those in the other countries and are sometimes better. Exceptions were cancer of the lung, large bowel, and breast, the first of which is explained by differences in the prevalence of smoking.

Mortality from cancer in relation to smoking: 50 years observations on British doctors.

A total of 34,439 male British doctors, who reported their smoking habits in November 1951, were followed, with periodic up date of changes in their habits, until death, emigration, censoring. or November 2001. Information was obtained about their mortality from 28 of the 30 types of cancer in men reviewed by the International Agency for Research on Cancer (no death was recorded from the other two). In all, 11 of the 13 types in men that the Agency classed as liable to be caused by smoking were significantly related to smoking and the findings for the other two, which caused only few deaths, suggested they might be. Of the 13 types in men for which the Agency found only sparse or inconsistent data and for which we had data, only two appeared to be possibly related (one positively, one negatively), and the 638 deaths for the summed group were clearly unrelated to smoking. Of the two types for which the Agency thought that the relationship with smoking might be due to bias or confounding, the findings for one (prostate cancer) tended to support the belief that smoking was unrelated, and those for the other (colorectal cancer) showed a weak relationship with smoking, which (in a small subset) could not be attributed to confounding with the consumption of alcohol.

Smoking and dementia in male British doctors: prospective study.

OBJECTIVE: To assess the possible association between smoking and dementia. DESIGN: Prospective study. SETTING: Cohort of British male doctors followed up since 1951. SUBJECTS: 34 439 male British doctors, with 24 133 deaths recorded. RESULTS: For all types of dementia combined the relative risk was 0.96 (95% confidence interval 0.78 to 1.18), based on 473 deaths at a mean age of 81 years. For probable or definite Alzheimer's disease, the relative risk in continuing smokers was 0.99 (0.78 to 1.25), based on 370 deaths at a mean age of 82 years. In aggregate, however, the other prospective studies indicate a direct, although not clearly significant, association between smoking and the onset of dementia in general and of Alzheimer's disease in particular. CONCLUSIONS: Contrary to previous suggestions persistent smoking does not substantially reduce the age specific onset rate of Alzheimer's disease or of dementia in general. If anything, it might increase rather than decrease the rate, but any net effect on severe dementia cannot be large in either direction.

Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths.

OBJECTIVE: To assess the hazards at an early phase of the growing epidemic of deaths from tobacco in China. DESIGN: Smoking habits before 1980 (obtained from family or other informants) of 0.7 million adults who had died of neoplastic, respiratory, or vascular causes were compared with those of a reference group of 0.2 million who had died of other causes. SETTING: 24 urban and 74 rural areas of China. SUBJECTS: One million people who had died during 1986-8 and whose families could be interviewed. MAIN OUTCOME MEASURES: Tobacco attributable mortality in middle or old age from neoplastic, respiratory, or vascular disease. RESULTS: Among male smokers aged 35-69 there was a 51% (SE 2) excess of neoplastic deaths, a 31% (2) excess of respiratory deaths, and a 15% (2) excess of vascular deaths. All three excesses were significant (P<0.0001). Among male smokers aged >/70 there was a 39% (3) excess of neoplastic deaths, a 54% (2) excess of respiratory deaths, and a 6% (2) excess of vascular deaths. Fewer women smoked, but those who did had tobacco attributable risks of lung cancer and respiratory disease about the same as men. For both sexes, the lung cancer rates at ages 35-69 were about three times as great in smokers as in non-smokers, but because the rates among non-smokers in different parts of China varied widely the absolute excesses of lung cancer in smokers also varied. Of all deaths attributed to tobacco, 45% were due to chronic obstructive pulmonary disease and 15% to lung cancer; oesophageal cancer, stomach cancer, liver cancer, tuberculosis, stroke, and ischaemic heart disease each caused 5-8%. Tobacco caused about 0.6 million Chinese deaths in 1990 (0.5 million men). This will rise to 0.8 million in 2000 (0.4 million at ages 35-69) or to more if the tobacco attributed fractions increase. CONCLUSIONS: At current age specific death rates in smokers and non-smokers one in four smokers would be killed by tobacco, but as the epidemic grows this proportion will roughly double. If current smoking uptake rates persist in China (where about two thirds of men but few women become smokers) tobacco will kill about 100 million of the 0.3 billion males now aged 0-29, with half these deaths in middle age and half in old age.

Emerging tobacco hazards in China: 2. Early mortality results from a prospective study.

OBJECTIVE: To monitor the evolving epidemic of mortality from tobacco in China following the large increase in male cigarette use in recent decades. DESIGN: Prospective study of smoking and mortality starting with 224 500 interviewees who should eventually be followed for some decades. SETTING: 45 nationally representative small urban or rural areas distributed across China. SUBJECTS: Male population aged 40 or over in 1991, of whom about 80% were interviewed about smoking, drinking, and medical history. MAIN OUTCOME MEASURE: Cause specific mortality, initially to 1995 but later to continue, with smoker versus non-smoker risk ratios standardised for area, age, and use of alcohol. RESULTS: 74% were smokers (73% current, only 1% former), but few of this generation would have smoked substantial numbers of cigarettes since early adult life. Overall mortality is increased among smokers (risk ratio 1.19; 95% confidence interval 1.13 to 1.25, P<0.0001). Almost all the increased mortality involved neoplastic, respiratory, or vascular disease. The overall risk ratios currently associated with smoking are less extreme in rural areas (1.26, 1.12, or 1.02 respectively for smokers who started before age 20, at 20-24, or at older ages) than in urban areas (1.73, 1.40, or 1.16 respectively). CONCLUSION: This prospective study and the accompanying retrospective study show that by 1990 smoking was already causing about 12% of Chinese male mortality in middle age. This proportion is predicted to rise to about 33% by 2030. Long term continuation of the prospective study (with periodic resurveys) can monitor the evolution of this epidemic.

Mortality from smoking worldwide.

Estimates are made of the numbers and proportions of deaths attributable to smoking in 44 developed countries in 1990. In developed countries as a whole, tobacco was responsible for 24% of all male deaths and 7% of all female deaths, rising to over 40% in men in some former socialist economies and 17% in women in the USA. The average loss of life for all cigarette smokers was about 8 years and for those whose deaths were attributable to tobacco about 16 years. Trends in mortality attributable to tobacco differed between countries. In some the mortality in middle age (35-69 years) had decreased by half in men since 1965; in others it was continuing to increase. In women, the proportion was mostly increasing, almost universally in old age. Mortality not attributable to smoking decreased since 1955 in all OECD (Organization for European Collaboration and Development) countries, by up to 60% in men and more in women. No precise estimate can be made of the number of deaths attributable to smoking in undeveloped countries, but the prevalence of smoking suggests that it will be large. In the world as a whole, some 3 million deaths a year are estimated to be attributable to smoking, rising to 10 million a year in 30-40 years' time.

Geographic association between urinary excretion of N-nitroso compounds and oesophageal cancer mortality in China.

Overnight urine samples were collected from approximately 60 male adults in each of 69 counties of China in 1989. Two specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids and nitrate were measured in urine samples and correlated with cumulative mortality rates for subjects aged between 0 and 64 years in the 1970s. Oesophageal cancer mortality rates were positively and significantly associated with (i) urinary levels of excreted N-nitrosoproline (NPRO) (after proline and ascorbic acid loading or proline loading only), (ii) N-nitrososarcosine levels, and (iii) nitrosation potential (the decrease in the amount of urinary NPRO after adding ascorbic acid to the proline load). There were also positive correlations between the urinary level of NPRO or other N-nitrosamino acids and that of nitrate. The urinary excretion of nitrate was associated with consumption of various nitrate-rich vegetables. The results suggest that N-nitroso compounds (NOC) or other nitrite-derived carcinogens are implicated in the aetiology of oesophageal cancer in China.

Treatment of advanced localised prostatic cancer by orchiectomy, radiotherapy, or combined treatment. A Medical Research Council Study. Urological Cancer Working Party--Subgroup on Prostatic Cancer.

A total of 277 patients with apparently localised prostatic cancer (T2-T4 NXMO) were allocated at random to receive radiotherapy alone (88), orchiectomy alone (90) and combined therapy (99) between 1980 and 1985. The main outcome measures were survival, time to appearance of metastases and treatment of local disease progression by further transurethral resection. Orchiectomy, whether alone or with radiotherapy, produced a significant delay in detection of metastases when compared with radiotherapy alone. There were no statistically significant differences between the 3 treatment groups in local disease control or in overall survival.

Mortality from tobacco in developed countries: indirect estimation from national vital statistics.

Prolonged cigarette smoking causes even more deaths from other diseases than from lung cancer. In developed countries, the absolute age-sex-specific lung cancer rates can be used to indicate the approximate proportions due to tobacco of deaths not only from lung cancer itself but also, indirectly, from vascular disease and from various other categories of disease. Even in the absence of direct information on smoking histories, therefore, national mortality from tobacco can be estimated approximately just from the disease mortality statistics that are available from all major developed countries for about 1985 (and for 1975 and so, by extrapolation, for 1995). The relation between the absolute excess of lung cancer and the proportional excess of other diseases can only be approximate, and so as not to overestimate the effects of tobacco it has been taken to be only half that suggested by a recent large prospective study of smoking and death among one million Americans. Application of such methods indicates that, in developed countries alone, annual deaths from smoking number about 0.9 million in 1965, 1.3 million in 1975, 1.7 million in 1985, and 2.1 million in 1995 (and hence about 21 million in the decade 1990-99: 5-6 million European Community, 5-6 million USA, 5 million former USSR, 3 million Eastern and other Europe, and 2 million elsewhere, [ie, Australia, Canada, Japan, and New Zealand]). More than half these deaths will be at 35-69 years of age: during the 1990s tobacco will in developed countries cause about 30% of all deaths at 35-69 (making it the largest single cause of premature death) plus about 14% of all at older ages. Those killed at older ages are on average already almost 80 years old, however, and might have died soon anyway, but those killed by tobacco at 35-69 lose an average of about 23 years of life. At present just under 20% of all deaths in developed countries are attributed to tobacco, but this percentage is still rising, suggesting that on current smoking patterns just over 20% of those now living in developed countries will eventually be killed by tobacco (ie, about a quarter of a billion, out of a current total population of just under one and a quarter billion).

Serum hormone levels in British and rural Chinese females.

The comparison of blood levels of oestradiol, testosterone, prolactin, and sex-hormone binding globulin (SHBG) was made of 3250 rural Chinese and 300 British women, aged 35 to 64. To reduce the number of assays performed the blood samples were combined so as to form 390 and 30 pools, respectively. The Chinese had significantly less oestradiol and testosterone. Prolactin levels were similar in both races. SHBG was significantly lower in postmenopausal British women. In the Chinese women, testosterone was positively and prolactin negatively correlated with breast cancer mortality.

Sex hormones in women in rural China and in Britain.

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.

Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China.

To examine the geographic association between Helicobacter pylori infection and gastric cancer, we have assessed the prevalence of IgG antibodies to H. pylori in plasma samples taken in 1983 from 1882 men, aged 35-64 years, in 46 rural counties of the People's Republic of China. The gastric cancer mortality rates in these countries in 1973-75 varied from 3 per 1,000 (cumulative rate, 0-64 years) to 69 per 1,000, while the proportions of the population positive for H. pylori antibodies (based on an average of about 41 men per county) varied from 28% to 96%. After correction for the limited number of blood samples per county, the estimated correlation between H. pylori antibody prevalence and gastric cancer mortality was 40% (p = 0.02). No other type of cancer showed a significant association with H. pylori.

Urinary riboflavin excretion after a load test in rural China as a measure of possible riboflavin deficiency.

Urinary excretion of riboflavin was measured in 3318 adults 4 h after an oral dose of riboflavin. Male and female subjects aged 35-64 years were selected from 65 mostly rural counties located in 24 provinces of China. Counties were selected to represent a range of seven of the most prevalent cancer mortality rates in China and within counties households were selected at random. Urinary riboflavin excretion levels after a load test, erythrocyte glutathione reductase activity coefficients (EGR-AC), dietary riboflavin intakes, and a large number of other biochemical, dietary, and environmental parameters were measured. Mean dietary intake of riboflavin was 75 per cent of the Chinese recommended dietary allowances (CRDA). Mean meat intake per reference man was very low (26.4 +/- 23.7 g/d) in comparison to Western standards and milk was not consumed at all in most counties. Mean EGR activity coefficients measured on 'blood pools' for both males (1.47 +/- 0.14) and females (1.48 +/- 0.16) indicated that more than two-thirds of the population surveyed was in the medium or high risk category of riboflavin deficiency. Using current reference standards of less than 1.4 mg for 4-h urinary excretion of riboflavin after a 5 mg load, more than 70 per cent of the individuals examined exhibited low levels usually associated with high risk of riboflavin deficiency. In view of the lack of specificity for clinical indications of riboflavin deficiency and the tentative validity of the present CRDA, the interpretation of the data is problematic. We suggest that the present CRDA for this vitamin is set too high and requires critical review and possibly some revision.

Serum beta-carotene and subsequent risk of cancer: results from the BUPA Study.

In the BUPA Study, a prospective study of 22,000 men attending a screening centre in London, serum samples were collected and stored. The concentration of beta-carotene was measured in the stored serum samples from 271 men who were subsequently notified as having cancer and from 533 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean beta-carotene level of the cancer subjects was significantly lower than that of their matched controls (198 and 221 micrograms l-1 respectively, P = 0.007). The difference was apparent in subjects from whom blood was collected several years before the diagnosis of the cancer, indicating that the low beta-carotene levels in the cancer subjects were unlikely to have been simply a consequence of pre-clinical disease. Men in the top two quintiles of serum beta-carotene had only about 60% of the risk of developing cancer compared with men in the bottom quintile. The study was not large enough to be able to indicate with confidence the sites of cancer for which the inverse association between serum beta-carotene and risk of cancer applied, though the association was strongest for lung cancer. The association may be due to beta-carotene affecting the risk directly or it may reflect an indirect association of cancer risk with some other component of vegetables or with a nonvegetable component of diet that is itself related to vegetable consumption.

Serum vitamin E and subsequent risk of cancer.

In a prospective study of about 22,000 men attending a screening centre, serum samples were collected and stored. The concentration of vitamin E (alpha-tocopherol) was measured in the stored serum samples from 271 men subsequently notified as having cancer and from 533 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean vitamin E level of the cancer subjects was not significantly different from that of their matched controls. The mean level in the cancer subjects who were diagnosed as having cancer before the elapse of one year from the date of blood collection was, however, significantly lower than the mean concentration of their matched controls (10.0 and 11.5 mgl-1 respectively, P = 0.003). For subjects whose cancers were diagnosed one or more years after blood collection the difference was not statistically significant either for all cancers or for cancers of six sites considered separately, viz. lung, colon and rectum, stomach, bladder, central nervous system and skin. The most likely explanation for these results is that the low vitamin E levels observed in these subjects were a metabolic consequence, rather than a precursor, of the cancer. This would explain, at least in part, the overall inverse association between serum vitamin E and risk of cancer observed in the published epidemiological studies on serum vitamin E and cancer.

Serum retinol and subsequent risk of cancer.

In a prospective study of about 22,000 men attending a well person screening centre, serum samples were collected and stored. The concentration of retinol was measured in the stored serum samples from 227 men subsequently notified as having cancer and from 454 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean serum retinol concentration of the cancer subjects who developed cancer before the elapse of one year since the time blood was collected was significantly lower than the mean concentration of their matched controls (641 and 722 micrograms l-1 respectively, P less than 0.001). For subjects whose cancer developed one to two years after blood had been collected, the difference was less (650 and 701 micrograms l-1 respectively, P less than 0.01). For subjects whose cancer developed three or more years after blood was collected, the mean retinol level was higher than in their controls, although not statistically significantly so (694 and 663 micrograms l-1 respectively). These findings suggest that the inverse association between serum retinol and risk of cancer that was previously observed was due to low serum retinol being a metabolic consequence of cancer rather than a precursor of cancer.