Biomedical subjects
P Boyle
Publications and source records attributed to P Boyle.
Assessment of screening for cancer.
Screening has a relevant role in and is likely to become an increasingly important instrument for cancer control in the near future. This overview summarizes some of the available evidence on the issue. Some of the opinions are well established. The apparent absence of consensus on other issues should be critically evaluated, too, because the evidence on some procedures is substantially more convincing than that on others. High costs, low compliance, poor curability, and substantial false positive rates, in a disease as relatively rare as cancer, often counterbalance in practice the theoretical benefits of diagnostic anticipation. In screening as well as in treatment for cancer, it is unlikely that major technical breakthroughs will occur in the near future. The evaluation of whether the benefits likely to be achieved by the screening program outweigh its disadvantages by a sufficient margin, therefore, should rely on large and carefully planned controlled studies.
Hodgkin's disease mortality in Europe.
Trends in mortality from Hodgkin's disease between mid 1950s and the late 1980s have been analysed for 16 western European and seven eastern European countries. In all western countries there were substantial falls in mortality from the late 1960s onwards, for an overall mean decline of 50% in both sexes, although these falls were somewhat larger in Nordic countries (approaching 70% in Denmark and Sweden), and more limited (20 to 30%) in Portugal, Spain and Greece. The reductions in Hodgkin's disease mortality were evident both in younger (under 35) and middle age (35 to 64 years), as well as in children under 15 and, in several countries, in the elderly (above 65), too. They were persistent up to the most recent calendar periods, with no evidence of flattening off. The pattern of trends in Hodgkin's disease mortality was largely different in Eastern Europe. Among seven countries examined, some fall was observed only in Bulgaria and Czechoslovakia, but other countries showed no consistent pattern and there was some increase, too. In absolute terms, the reductions in Hodgkin's disease mortality in Western Europe correspond to the avoidance of over 3,000 deaths per year. This stresses the importance and urgency of improving the availability of currently defined knowledge and resources for treatment of Hodgkin's disease in Eastern Europe.
Risk factors for gallstone disease requiring surgery.
Risk factors for cholelithiasis were investigated in a case-control study conducted in northern Italy on 195 incident cases of gallstone disease requiring surgery (119 females, 76 males) and 1122 controls in hospital for acute, non-digestive tract, non-neoplastic conditions. There was no consistent association with socio-demographic indicators, such as marital status, education and social class nor with smoking and coffee consumption. The relative risk of cholelithiasis decreased with increasing alcohol consumption: compared with non-drinkers, the odds ratio (OR) was 0.8 for one to three drinks per day and 0.5 for over three. A direct association was observed with measures of body weight: relative to leaner individuals, the multivariate ORs were 1.2, 2.1 and 2.4 for subsequent levels of body mass. These trends in risk were statistically significant, consistent in the two sexes, and not apparently modified by adjustment for major identified potential confounding factors. History of hepatitis and liver cirrhosis were reported more frequently by cases, but it is difficult to assess the role of recall bias on these risk factors. No association was found with diabetes, thyroid disease and several digestive tract disorders. For females, no consistent pattern of risk was observed up to four births, but women with five or more births had an OR of 2.9 (95% confidence interval (Cl) = 1.1-7.3). The risk decreased with increasing age at first and last birth, both trends being statistically significant. Overweight and alcohol consumption were the most important risk and protective factors respectively for cholelithiasis requiring surgical intervention in this population.
Dietary indicators of oral and pharyngeal cancer.
The relationship between frequency of consumption of a selected number of indicator foods and oral and oropharyngeal cancer risk was analysed in a case-control study conducted in Northern Italy on 105 cases of oral and pharyngeal cancer and 1169 controls in hospital for acute, non-neoplastic or digestive diseases. Besides significant and strong direct associations with tobacco (relative risk, RR = 11.0 for current versus never smokers) and alcohol (RR = 5.8 for upper versus lower consumption tertile), consumption of six food items (milk, meat, cheese, carrots, green vegetables and fruit) were inversely and significantly related to oral and pharyngeal cancer risk. The strongest protection was apparently related to frequent fruit consumption, with RRs of 0.8 and 0.2 in the two highest tertiles. Allowance for major potential confounding factors, including tobacco, alcohol and social class indicators explained only part of the dietary correlates observed. The two items remaining significant after multivariate analysis were fruit (RR = 0.3 for the upper tertile) and alcohol (RR = 3.8 for the upper tertile). The associations observed may simply reflect a generally poorer nutritional status in the cases, although the observation that fruit consumption appears to be a particularly important protective factor against oropharyngeal cancer is of potential interest, in terms of aetiological clues and preventive implications.
Analysis of quantitative data by quantiles in epidemiologic studies: classification according to cases, noncases, or all subjects?
Quantitative exposure data in epidemiologic studies are frequently analyzed by ordered categories. Categorization by quantiles can be based on the distribution of (1) cases, (2) noncases, and (3) all subjects. The advantages of the three schemes in determining quantiles were compared. They were found to give the same power regarding a test for trend over a wide range of study situations. Considerations on the representativeness and the ease of the analysis implementation could dictate the choice of the categorization scheme.
Dairy products and the risk of prostatic cancer.
Dietary indicators of prostatic cancer risk were analyzed in a case-control study conducted in Northern Italy on 96 histologically confirmed cases and 292 controls in hospital for acute, nonneoplastic or genital tract diseases. There was a significant trend in risk as regards frequency of milk consumption: compared with nondrinkers or occasional milk drinkers, the relative risk (RR) was 1.2 (95% confidence interval, Cl, 0.7-1.9) for 1 or 2 glasses per day and 5.0 (95% Cl 1.5-16.6) for 2 or more glasses per day. By contrast, no consistent association was observed with measures of cheese or butter intake. This might, at least in part, be attributable to the lower measurement errors for milk (which tends to be consumed in regular and uniform patterns) as compared with other dairy products. However, the interpretation of these findings is not clear, since other sources of animal fat, like eggs or meat, as well as a summary fat score, were unrelated to prostatic cancer. Although these limitations and uncertainties are substantial, this study provides further evidence that elevated milk consumption may be an indicator of prostatic cancer risk.
Diet and urine estrogens among postmenopausal women.
Creatinine-adjusted levels of estrone, estradiol and estriol were determined in overnight urine specimens from 88 postmenopausal women from Athens, Greece, and were correlated with daily nutrient intakes estimated through a semiquantitative food frequency questionnaire. Although obesity was positively and significantly related to all three urinary estrogens and their total, none of the investigated macro- or micronutrients was significantly or suggestively associated to any of these urinary estrogens, after controlling for energy intake, reproductive and biosocial variables. These results suggest that quantitative rather than qualitative aspects of nutrition affect the levels of postmenopausal estrogens, although endogenous factors could also be responsible for the association of these estrogens with obesity. Alcohol intake was also positively associated with urinary estrogens (mainly estrone and estradiol), after controlling for energy intake, obesity and the other indicated variables.
Epidemiology of benign prostatic hyperplasia: present knowledge and studies needed.
Despite being such a common condition, morphologically prevalent in 88% of autopsies of old (greater than 80 years) men, little epidemiologic research has been undertaken on benign prostatic hyperplasia (BPH). The prevalence of BPH, and probably the incidence, increases with age although the belief that BPH is a direct consequence of aging per se still awaits proof. Many observers have concluded that the age association reflects age-related hormonal changes, although this also requires proof. BPH is a very common condition in aging men: 3 in every 10 may ultimately require surgery for this condition if current estimates of prevalence are correct. Despite its common occurrence, little is known with any degree of certainty about risk factors for BPH apart from being male, being old, and having had a pair of functioning testicles since puberty. There are good reasons why the epidemiology of BPH has remained poorly understood although the application of more epidemiologic thought could pay great dividends, particularly if prostate screening programs could be exploited maximally.
Cancer registration: principles and methods. Statistical methods for registries.
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Capillary blood cell velocity is reduced in fever without hypotension.
Capillary blood cell velocity was measured in a group of normotensive febrile patients as a basis for further study into the microvascular physiology of febrile hypotensive patients with sepsis. Television videomicroscopy was used to record the capillary blood cell movement in the finger nailfold. Analysis of all moving gaps in the red cell column seen during a minimum of 2 minutes was done by the frame-by-frame technique and mean blood cell velocity derived. Core (external auditory meatus) and skin (finger) temperature were also measured. Subjects (n = 6) were sex and skin temperature matched to controls. Although the mean skin temperature of subjects [28.73 degrees C, SD = 0.28] was not significantly different to controls [30.63 degrees C, SD = 3.11; p less than 0.05] the mean velocity was significantly reduced in the febrile subject group [0.28 mm/sec, SD = 0.17] as compared with controls [0.56 mm/sec, SD = 0.22; p less than 0.05]. It is likely therefore that these skin vessels vasoconstrict as part of the integrated response to reduce heat loss.
Projections to the end of the century of mortality from major cancer sites in Italy.
We used an age-period-cohort model with arbitrary constraints on the parameters, fitted to the mortality data for the period 1955-84, to project rates in mortality from all cancers and 11 major cancer sites in Italy for the period 1985-1999. For all neoplasms considered, using estimated age and cohort values, two models were fitted, one based on constant period effects, and one on a linear regression on the logarithm of the six calendar periods. Furthermore, "a priori" defined coefficients based on epidemiologic inferences were given to period values for tobacco-related neoplasms (below unity for males, above unity for females, on the basis of recent trends in tobacco prevalence in the two sexes), for breast and ovarian cancer (in relation to the potentially different effect of oral contraceptives, other female hormones, reproductive factors and treatment on these neoplasms), and for total cancer mortality. This produced a range of potential estimates, which were reasonably similar for neoplasms (such as stomach, intestines, breast, ovary or prostate) for which no major change in slope of the cohort effects was evident, but wider (i.e., between 188 and 264/100,000 males aged 40 to 79 in 1995-99) for lung or other tobacco-related cancers. Although this range of variation is far from negligible, the estimated values indicate that lung cancer among Italian males aged 40 to 79, even under the more optimistic assumption, will probably be higher at the end of the century than in the early 1980's, and that lung cancer alone will account for 35 to 42% of all cancer deaths in males between 40 and 79 years. Though any prediction has, by definition, inherent difficulties and uncertainties, cancer mortality in the near future will be strongly influenced by age and cohort effects already known, and hence its projections may offer some indication of public health relevance.
Is the increased incidence of primary malignant brain tumors in the elderly real?
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Medical history and primary liver cancer.
The relationship between selected aspects of medical history and the risk of primary liver cancer was analyzed in a hospital-based case-control study conducted in Northern Italy on 242 patients with histologically or serologically confirmed hepatocellular carcinoma and 1169 controls in hospital for acute, nonneoplastic, or digestive diseases. Significant associations were observed for clinical history of hepatitis [odds ratio (OR), 3.7; 95% confidence interval (CI), 2.3-5.9], cirrhosis (OR, 16.8; 95% CI, 9.8-28.8), and three or more episodes of transfusion in the past (OR, 2.2; 95% CI, 1.4-4.1). Among other diseases considered, there was a significant association with diabetes (OR, 2.5; 95% CI, 1.7-3.8), and a protection by history of drug allergies (OR, 0.5; 95% CI, 0.2-0.9). These associations were not appreciably modified by allowance for major identified potential confounding factors and were observed for diseases occurring less than 5 or 5 or more years before liver cancer diagnosis, although for cirrhosis the risk was higher in the short term occurrences (OR, 50). For hepatitis, the association was more evident at older ages, confirming the long lead time between infection and cancer occurrence, while for diabetes it was stronger (or restricted) to cases aged less than 60, suggesting a possible specific role of type I diabetes. While for hepatitis, cirrhosis, and blood transfusion this study offers further quantitative estimates of risk in a European population, the possible direct association with diabetes and protection by drug allergy were unexpected, lacked plausible biological or previous epidemiological support, and should be simply regarded as working hypotheses for further work.
Dietary indicators of laryngeal cancer risk.
The relationship between frequency of intake of a selected number of indicator foods and the risk of laryngeal cancer was investigated in a case-control study conducted in northern Italy on 110 males with histologically confirmed cancer of the larynx and 843 controls in the hospital for acute, nonneoplastic or respiratory diseases. Significant direct associations were observed with tobacco [relative risk (RR) = 5.8 for current versus never smokers] and alcohol (RR = 2.3 for the upper versus lower tertile of consumption), while the frequency of consumption of three food items was inversely related with laryngeal cancer risk. These were fish (RR = 0.6 for the upper tertile), green vegetables (RR = 0.4), and fresh fruit (RR = 0.3). Multiple logistic regression analysis, including simultaneously major nondietary covariates and various food items, suggested that the strongest and most consistent protective effect was given by fruit. These findings can be generally interpreted as an indication that a "poorer" diet is related to a raised risk of laryngeal cancer, although the confirmed observation that fruit appears to be the main protective dietary factor against cancers of the upper respiratory and digestive tract is of potential interest and may suggest useful etiological clues. Dietary findings were similar in different strata of alcohol and tobacco consumption.
Some further consideration on the role of oral contraceptives in breast carcinogenesis.
Available evidence concerning oral contraceptives and their potential interaction with reproductive history on breast cancer risk is reviewed. The relative risks in 15 out of 15 studies were above unity among younger women (i.e., below age 35 and perhaps up to 45) for long-term oral contraceptive use, although apparent heterogeneities emerged in the risk estimates. The overall evidence is reassuring in subsequent age groups, whereas the modifying effects or interactions between oral contraceptives, reproductive factors and breast cancer risk are still largely undefined. Thus we suggest that, besides chance and bias, the apparent discrepancies between various studies should be considered within the framework of the complex time- and age-effects of hormone-related risk factors on breast carcinogenesis.
Alcohol, beer and cancer of the pancreas.
The relationship between total alcohol consumption and intake of beer, wine and spirits and the risk of cancer of the pancreas was re-assessed in a pooled analysis of 3 case-control studies of pancreatic cancer from Italy, France and Switzerland, providing a total data-set of 494 cases and 1,704 controls. Logistic regression was used to obtain relative risks adjusted for study, age, sex, smoking and socio-economic status. Relative to non-drinkers, the risk estimates for subsequent levels of alcohol consumption were close to unity, and there was no evidence of a trend in risk with dose: the point estimate for more than 8 drinks per day was 0.8 (95% Confidence Interval, CI = 0.5-1.3). Likewise, no consistent association was observed for consumption of wine, beer or spirits: the relative risks for the highest consumption levels were 1.0 for wine, 0.9 for beer and 0.9 for spirits. No significant interaction was observed with study centre, sex or smoking habits. Given the large size of the data-set, of the consistency and the replication of findings across the 3 different studies, and of the elevated alcohol consumption of these populations, the present analysis gives reassuring evidence on the alcohol and pancreatic cancer issue in relation to total consumption of alcohol, of beer and of other alcoholic beverages.
The consumption of tobacco, alcohol and the risk of adenocarcinoma in Barrett's oesophagus.
The relationship between tobacco, alcohol and the risk of oesophageal adenocarcinoma in Barrett's oesophagus was evaluated in an endoscopy-clinic-based case-control study of 30 histologically confirmed cases of adenocarcinoma and 140 controls with Barrett's oesophagus but no evidence of malignant lesions. Among the cases, 18 (60%) were non-smokers and 14 (47%) non-drinkers, the corresponding proportions in the controls being 52% and 44%. Thus, there was no apparent relation between tobacco, alcohol and the risk of adenocarcinoma of the oesophagus, the age- and sex-adjusted point estimates being 1.0 for moderate and 0.9 for heavy smokers, 0.7 and 1.5 respectively for moderate and heavy drinkers. Upper 95% confidence limits were 1.6 for ever-use of tobacco and 1.9 for ever alcohol drinking. The findings of this study, although based on a limited number of cases, indicate that alcohol and tobacco are unlikely to play a major role in the aetiology of adenocarcinoma in Barrett's oesophagus.