Tobacco smoking and prostate cancer: time for an appraisal.
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Biomedical subjects
Publications and source records attributed to F Levi.
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BACKGROUND: It is not clear whether the purported association of leanness with cancer of the oral cavity and pharynx was due to cancer-related weight loss or to the influence of factors associated with leanness. PATIENTS AND METHODS: Seven hundred fifty-four incident cases of cancers of the oral cavity and pharynx and 1775 controls, admitted to hospital for acute, non-neoplastic diseases, in Italy and Switzerland. Questionnaire included height, lifetime history of weight and of physical activity, waist and hip measurements, and a validated food-frequency section. RESULTS: Leanness at diagnosis was associated with elevated risk in men (adjusted odds ratio, OR for 5-unit decrease in body-mass index, BMI = 1.9; 95% confidence interval (CI): 1.6-2.2 in men). Male cases were significantly leaner than control subjects at the age of 30 and of 50. Thinner women also had an increased risk, but the inverse association with BMI was non linear. In both sexes, the association with leanness was restricted to smokers and moderate/heavy drinkers, but was not accounted for by drinking and smoking habits, nor by differences in physical activity or dietary habits. CONCLUSIONS: Leanness appears to be an early marker of some unknown biological effect of smoking and/or of alcohol abuse, which may contribute to the prediction of cancers of the oral cavity and pharynx. Cessation of smoking and substantial reduction of alcohol intake may improve nutritional status, besides stopping carcinogen exposure.
OBJECTIVE: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. METHODS: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. RESULTS: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromsø, and Vaud. Conversely, the ORs for the studies in Los Angeles. Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR = 0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR = 0.65, 95% CI 0.48-0.88). CONCLUSION: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.
BACKGROUND: Trends in cancer mortality for the elderly have long been unfavourable. MATERIALS AND METHODS: Mortality from 12 major cancer sites, plus total cancer mortality at age 65-84 in 23 European countries, the US and Japan was analyzed. RESULTS: Between the late 1980s and the late 1990s total cancer mortality at age 65 to 84 has been declining in the European Union (UE) (-5.5% in males, -4.5% in females), in United States (US) males (-2.3%), but not females (+4.4%), and in Japanese females (-5.6%), but not males (+6.3%). Cancer mortality in the elderly rose for both sexes in eastern Europe. Gastric cancer mortality declined in all the areas. Lung cancer rates declined over the last decade by 8.5% in males in the EU. and by 0.9% in the US. Rates were still increasing in eastern Europe, in Japanese males and in females in all areas. Pancreatic mortality rates were increasing in both sexes in the EU and Japan up to the late 1980s, and in eastern Europe up to the 1990s, whereas rates for US males have been declining over recent years. Breast cancer mortality has declined over the last decade by 8% in the US and by 3% in the EU, while it has risen in eastern Europe and in Japan. Mortality from breast and prostate as well as ovarian cancer remained however low in elderly Japanese. Prostate cancer mortality declined in the EU and in the US, whereas it rose in eastern Europe and in Japan. Mortality from lymphomas and multiple myeloma rose in both sexes and various geographic areas, but improved diagnosis and certification may have played a role in these trends. Mortality from leukemia in the elderly increased in eastern Europe and Japan. but was stable in the US and the EU. CONCLUSIONS: Cancer mortality in the elderly has stopped systematically rising, and is on the decline in males since the late 1980s.
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Trends of skin cancer incidence by histotype in the Swiss Canton of Vaud (608,000 inhabitants) between 1976 and 1992 were updated on the basis of 6720 further skin cancers registered over the period 1993-1998. Trends in the last period were downwards for squamous cell carcinoma in both sexes, still on the rise for basal cell carcinoma, and levelled off for malignant melanoma in females.
In this paper, we propose a new scheme for operating an atomic fountain frequency standard. A sequence of time-spaced balls of atoms, launched over non-overlapping trajectories, makes possible a reduction of the atomic density and consequently the cold collision frequency shift by one order of magnitude without significant reduction of the useful signal and of the overall stability of the clock. The ultimate accuracy of a Cs fountain could be improved below the 10(-15) level currently achieved in operating clocks.
Thyrotropin (TSH) and the gonadotropins (FSH, LH, hCG) are a family of heterodimeric glycoprotein hormones composed of two noncovalently linked subunits, alpha and beta. We have recently converted the hTSH heterodimer to a biologically active single chain (hTSHbeta.CTPalpha) by fusing the common alpha-subunit to the C-terminal end of the hTSH beta-subunit in the presence of a approximately 30-amino acid peptide from hCGbeta (CTP) as a linker. The hTSHbeta.CTPalpha single chain was used to investigate the role of the N-linked oligosaccharides of alpha- and beta-subunits in the secretion and function of hTSH. Using overlapping PCR mutagenesis, two deglycosylated variants were prepared: one lacking both oligosaccharide chains on the alpha-subunit (hTSHbeta.CTPalpha(1+2)) and the other lacking the oligosaccharide chain on the beta-subunit (hTSHbeta.CTPalpha(deg)). The single chain variants were expressed in CHO cells and were secreted into the medium. hTSH variants lacking the oligosaccharide chains were less potent than hTSHbeta.CTPalpha wild-type with respect to cAMP formation and thyroid hormone secretion in cultured human thyroid follicles. Both deglycosylated variants competed with hTSH in a dose-dependent manner. The hTSHbeta.CTPalpha(1+2) variant blocked cAMP formation and thyroid hormone secretion stimulated by hTSH as well as by the antibody, thyroid-stimulating immunoglobulins, responsible for the most common cause of hyperthyroidism, Graves disease. Thus, this variant behaves as a potential antagonist, offering a novel therapeutic strategy in the treatment of thyrotoxicosis caused by Graves' disease and TSH-secreting pituitary adenoma.
Between 1992 and 1997 we conducted a case-control study of oesophageal cancer in 3 areas of northern Italy. Cases were 304 patients (29 women), ages 39-77 years (median age 60 years), with a first incident squamous-cell carcinoma (SCC) of the oesophagus. Controls were 743 patients (150 women), ages 35-77 years (median age 60 years), admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. We derived estimates of daily dietary intake of 6 macronutrients, cholesterol, and 20 micronutrients or minerals from a validated food-frequency questionnaire, including 78 food groups and recipes and 15 questions on individual eating patterns. After allowance for age, gender, area of residence, education, body mass index, physical activity, smoking habit, alcohol consumption and energy intake, most micronutrients were inversely associated with oesophageal SCC risk. Highly significant associations emerged for monounsaturated fatty acids [odds ratio (OR) in highest vs. lowest intake quintile = 0.5]; carotene (OR = 0.3); lutein + zeaxanthin (OR = 0.4); vitamin C (OR = 0.4); and niacin (OR = 0.5). Only retinol appeared to be positively related to risk (OR = 1.9). The effect of the above nutrients, expressed as ORs, appeared to be similar in non-smokers and smokers, and non/light drinkers and heavy drinkers.
Meat intake has been positively associated with risk of digestive tract cancers in several epidemiological studies, while data on the relation of meat intake with cancer risk at most other sites are inconsistent. The overall data set, derived from an integrated series of case-control studies conducted in northern Italy between 1983 and 1996, included the following incident, histologically confirmed neoplasms: oral cavity, pharynx and esophagus (n = 497), stomach (n = 745), colon (n = 828), rectum (n = 498), liver (n = 428), gallbladder (n = 60), pancreas (n = 362), larynx (n = 242), breast (n = 3,412), endometrium (n = 750), ovary (n = 971), prostate (n = 127), bladder (n = 431), kidney (n = 190), thyroid (n = 208), Hodgkin's disease (n = 80), non-Hodgkin's lymphomas (n = 200) and multiple myelomas (n = 120). Controls were 7,990 patients admitted to hospital for acute, non-neoplastic conditions unrelated to long-term modifications in diet. The multivariate odds ratios (ORs) for the highest tertile of red meat intake (>/=7 times/week) compared with the lowest (</=3 times/week) were 1.6 for stomach, 1.9 for colon, 1.7 for rectal, 1.6 for pancreatic, 1.6 for bladder, 1.2 for breast, 1.5 for endometrial and 1.3 for ovarian cancer. ORs showed no significant heterogeneity across strata of age at diagnosis and sex. No convincing relation with red meat intake emerged for cancers of the oral cavity, pharynx and esophagus, liver, gallbladder, larynx, kidney, thyroid, prostate, Hodgkin's disease, non-Hodgkin's lymphomas and multiple myeloma. For none of the neoplasms considered was there a significant inverse relationship with red meat intake. Thus, reducing red meat intake might lower the risk for several common neoplasms.
The relation between selected micronutrients and oral and pharyngeal cancer risk was investigated using data from a case-control study conducted between January 1992 and November 1997 in Italy and Switzerland. Cases were 754 incident, histologically confirmed oral cancers (344 of the oral cavity and 410 of the pharynx) admitted to the major teaching and general hospitals in the study areas. Controls were 1,775 subjects with no history of cancer admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were computed after allowance for age, sex, center, education, occupation, body mass index, smoking and drinking habits and non-alcohol energy intake. Micronutrients were analyzed both as continuous variables and in quintiles. In the former case, the unit was set to 1 SD of the distribution of controls. ORs for the continuous analysis were 0.95 for retinol, 0.61 for carotene, 0.91 for lycopene, 0.83 for vitamin D, 0.74 for vitamin E, 0.63 for vitamin C, 0.82 for thiamine, 0.87 for riboflavin, 0.59 for vitamin B6, 0.61 for folic acid, 0.62 for niacin, 0.91 for calcium, 0.88 for phosphorus, 0.65 for potassium, 0.82 for iron, 0.67 for non-alcohol iron and 0.89 for zinc; the 95% confidence interval excluded one for carotene, vitamin C and E, thiamine, vitamin B6, folic acid, niacin, potassium and iron. ORs were similar for the 2 sexes and in strata of age. When the combined intake of vitamins C and E and carotene was considered, the protective effect of each nutrient was more marked or restricted to subjects with low intake of the other 2. The association with vitamin C and carotene was independent of smoking and drinking habits, while that with vitamin E was less evident in those heavily exposed to alcohol or tobacco. In general, the more a micronutrient was correlated to total vegetable and fruit intake, the stronger was its protective effect against oral cancer.
BACKGROUND: To analyze the mortality from the eight main cancer sites in men and women from Spain between 1955-1994. MATERIAL AND METHODS: Age-standardized mortality rates were computed. RESULTS: In men, an increase in lung cancer mortality as well as in the other 8 sites was registered, except for stomach cancer. In women, breast, ovary, and pancreas cancer mortality continue to increase. CONCLUSIONS: Cancer mortality in Spain has dismal trends. This fact implies the need of strong interventions.
A strong, dose-dependent association exists between alcohol consumption and risk of cancer of the oral cavity and pharynx. The impact on risk of temporal aspects of drinking habits has been inadequately evaluated. Our case-control study included 754 individuals with incident cancer of the oral cavity and pharynx (median age 57) and 1,775 controls (median age 57) in the hospital for acute, non-neoplastic diseases who were interviewed in 2 Italian areas and in the Swiss Canton of Vaud between 1992 and 1997. The questionnaire included lifetime drinking and smoking habits. No influence of age at starting or duration of alcohol drinking was found. Risk increased substantially with the increase of weekly alcoholic drinks [Odds Ratios (OR) for >/= 91 drinks/week vs. never drinkers = 11.6]. Risk in former compared with current drinkers was 1.9-fold elevated. However, among individuals who had also stopped smoking, former drinkers showed lower ORs than current drinkers. The persistence of risk elevation several years after drinking cessation suggests that the role of alcohol is complex and it probably affects more than one stage of oral carcinogenesis. It remains to be clarified which impact prevention-driven drinking cessation may have on the excess of cancer of the oral cavity and pharynx due to elevated alcohol intake.
Upward trends in incidence and mortality from primary liver cancer have been reported from Japan, the USA and a few European countries. Thus, we systematically reviewed trends in age-standardised death certification rates from primary liver cancer between 1970 and 1996 in 20 European countries providing data for the World Health Organisation database. Overall age-standardised (world population) mortality rates were approximately stable or showed no consistent trends in seven countries, including Bulgaria and Hungary (with exceedingly high rates), Finland, The Netherlands and the UK. Moderate rises were observed in Austria, Germany and Switzerland, and much larger upward trends in France and Italy, particularly for males. Downward trends were observed in both sexes in Belgium, Spain, Ireland, Greece and several Scandinavian countries. The per cent change in rates per year ranged, for males, from -7.4% for Ireland and -5.1% for Spain to +4.4% for Italy and +8.6% for France. Trends were more favourable in women, with 15 out of 20 countries showing downward trends in rates, and moderately more favourable in middle age (45-64 years) and, in major European countries, in young adults (20-44 years of age). In conclusion, trends in liver cancer mortality in Europe are heterogeneous. The fall in mortality in countries like Spain may be largely explained by improvements in the distinction between primary and secondary liver neoplasms, whereas upward trends in Central Europe and Italy are likely to be, at least in part, real. Increases in infection with the hepatitis C virus, and improved and increased searches for liver cancer in cirrhotic patients are two of the likeliest explanations for these observations.
The association between dietary intake of various micronutrients and colorectal cancer risk was analysed using data from a case-control study conducted between 1992 and 1997 in the Swiss Canton of Vaud. Cases were 223 subjects (142 (64%) males, 81 (36%) females; median age 63 years) with incident, histologically confirmed colon (n=119; 53%) or rectal (n=104; 47%) cancer, and controls were 491 subjects (211 (43%) males, 280 (57%) females; median age 58 years; range 27-74) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions, unrelated to long-term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire (FFQ). Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity, and total energy and fibre intake. No significant association was observed for calcium, retinol, folate, vitamin D or E. The risk of colorectal cancer was directly associated with measures of iron intake (OR=2.43 for the highest tertile, 95% confidence interval (CI): 1.2-5.1) and inversely associated with vitamin C (OR=0.45; 95% CI: 0.3-0.8), and non-significantly with total carotenoids (OR=0.66, 95% CI: 0.4-1.1). Among various individual carotenoids considered, inverse associations were observed for alpha-carotene, beta-carotene and lutein/zeaxanthin. These findings were consistent across the strata of gender and age, and support the hypothesis that selected micronutrients have a favourable effect on colorectal carcinogenesis.
After the peak rate reached in 1988, moderate but steady declines were observed over the last decade in total cancer mortality rates in the European Union (EU). Such a decline was over 7% for both sexes combined over the period of 1988-1996 (i.e. from 147.0 to 136.4/100,000, world standard population). The declines in cancer mortality correspond to the avoidance of approximately 70,000 deaths in 1996 in the EU compared with the 1988 rates. The major determinants of these favourable trends were lung (-7.7%), stomach (-24.8%), intestines (-12.4%), breast (-7.1%), uterus, mainly cervix (-20.6%), and leukaemias (-8.3%) and, after 1992, a levelling off of prostate cancer rates.
On the basis of overall national death certification data, it is not possible to analyse mortality from cervical cancer in Europe, since 20-65% of deaths from uterine cancer in largest countries are still certified as uterus, unspecified. We analysed, therefore, age-standardised death certification rates from uterine cancer between 1960 and 1998 in women aged 20-44 years, since most deaths from uterine cancer below the age of 45 years arise from the cervix. In all Western European countries, except Ireland, substantial declines in cervical cancer mortality in younger women were observed, although the falls were larger and earlier for some Nordic countries. The trends were irregular in the UK, with earlier declines between 1960 and 1970, followed by a rise between 1970 and 1985, and a subsequent fall. In Ireland, mortality from uterine cancer at age 20 to 44 years has been rising since the early 1980s, to reach 3.4/100000 in 1995-1996. In Eastern Europe, some fall in mortality was observed in Hungary and Poland, while trends were upwards in Romania since 1980, and in Bulgaria. In all these countries, moreover, absolute rates remained appreciably higher than in most of Western Europe, and in the late 1990s there was over a 10-fold variation between the highest rates in Romania (10.6/100000 women aged 20-44 years) and the lowest ones in Finland (0.5/100000) or Sweden (0.9/100000). Within the European Union, the variation was over 6-fold, the highest rates being registered in Ireland (3. 4/100000) and Portugal (3.2/100000). The declines registered in cervical cancer mortality in young women were largely due to screening, and the persisting variations in mortality across Europe underline the importance of the adoption of organised screening programmes, with specific urgency in Eastern Europe.