Eva Negri

Although several studies have been conducted, the relation between diet and prostate cancer remains unclear. The role of a wide range of foods on the risk of prostate cancer has thus been analyzed in a case-control study conducted in Italy between 1991 and 2002. Cases were 1,294 patients below age 75 years with incident, histologically confirmed carcinoma of the prostate; controls were 1,451 subjects below age 75 years admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for major potential confounding factors, including calorie intake. Among the 19 food groups considered, 4 showed some significant association with prostate cancer risk. A significant trend of increasing risk with more frequent consumption was found for milk and dairy products (OR = 1.2 for highest vs. lowest quintile, p = 0.03) as well as bread (OR = 1.4, p = 0.01), whereas inverse associations were observed for soups (OR = 0.8, p = 0.02) and cooked vegetables (OR = 0.7, p = 0.01). This uniquely large study on prostate cancer and diet in a southern European population confirms that no strong association exists between any specific foods and prostate cancer, apart from an increased risk for milk and dairy products and a possible protective effect of vegetables.

The relationship between diabetes mellitus and primary liver cancer was investigated in a case-control study conducted in Italy between 1984 and 1996 on 428 cases with incident, histologically confirmed hepatocellular carcinoma, 59 with gallbladder and bile duct cancer, and 1,502 control subjects in the hospital for acute non-neoplastic diseases. Sixty-four cases of hepatocellular carcinoma vs. 87 controls reported a history of diabetes, corresponding to an odds ratio (OR) of 2.3 after allowance for age, sex and area of residence, and of 2.1 [95% confidence interval (CI) = 1.4-3.2] after further allowance for alcohol and tobacco consumption, history of hepatitis and liver cirrhosis, body mass index and history of liver cancer in first-degree relatives. The ORs were similar both for subjects diagnosed with diabetes below age 45, who most likely had insulin-dependent diabetes, and for those diagnosed later, who were likelier to have non-insulin-dependent diabetes. The OR was 2.3 for subjects whose diabetes was diagnosed <5 years before diagnosis of liver cancer, 1.9 for those diagnosed 5-9 years in advance and 2.2 for those diagnosed since 10 years or more. Five cases of gallbladder and bile duct cancer reported a history of diabetes: the corresponding OR was 1.2 (95% CI 0.5-2.9). The OR of hepatocellular carcinoma was 2.4 for males and 2.0 for females, 3.0 for subjects diagnosed with liver cancer under age 60 and 1.8 for those diagnosed at age 60 or over. None of the other covariates considered, including education, history of hepatitis, liver cirrhosis and alcohol drinking showed any meaningful modifying effect or interaction. The potential pathogenic mechanisms include liver alteration-and consequent cell proliferation-in subjects with diabetes. Thus a history of diabetes mellitus could explain about 8% (95% CI 5-11) of cases of liver cancer in this population.

After a steady increase since the 1950s, laryngeal cancer mortality had tended to level off since the early 1980s in men from most European countries. To update trends in laryngeal cancer mortality in Europe, age-standardized (world standard) mortality rates per 100,000 were derived from the WHO mortality database for 33 European countries over the period 1980-2001. Jointpoint analysis was used to identify significant changes in mortality rates. In the European Union (EU) as a whole, male mortality declined by 0.8% per year between 1980 and 1989, by 2.8% between 1989 and 1995, by 5.3% between 1995 and 1998, and by 1.5% thereafter (rates were 5.1/100,000 in 1980-1981 and 3.3/100,000 in 2000-2001). This mainly reflects a decrease in rates in men from western and southern European countries, which had exceedingly high rates in the past. Male laryngeal mortality rose up to the early 1990s, and leveled off thereafter in several countries from central and eastern Europe. In 2000-2001 there was still a 10-15-fold variation in male laryngeal mortality between the highest rates in Croatia (7.9/100,000) and Hungary (7.7/100,000) and the lowest ones in Sweden (0.5/100,000) and Finland (0.8/100,000). Laryngeal cancer mortality was comparatively low in women from most European countries, with stable rates around 0.3/100,000 in the EU as a whole over the last 2 decades. Laryngeal cancer trends should be interpreted in terms of patterns and changes in exposure to alcohol and tobacco. Despite recent declines, the persistence of a wide variability in male laryngeal cancer mortality indicates that there is still ample scope for prevention of laryngeal cancer in Europe.

The relationship between various body size indices and breast cancer risk before and after menopause was elucidated by means of a case-control study conducted between June 1991 and April 1994 in 6 Italian centers on 2,569 patients aged below 75 with histologically confirmed breast cancer, and on 2,588 controls admitted to the hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. Weight and, more consistently, body mass index (BMI, kg/m2) at diagnosis were inversely related to pre-menopausal breast cancer risk and directly to post-menopausal risk. An 8-unit increase in BMI resulted in an odds ratio of 0.8 for pre-menopausal and of 1.2 (significant) for post-menopausal women. Risk seemed to increase gradually after menopause in the 7th (OR for an 8-unit BMI increase, 1.3) and 8th decades (OR, 1.6) of life. Conversely, height, waist-to-hip ratio, bra cup size and weight (or BMI) in adolescence and in young adulthood did not exert a significant or consistent influence on breast cancer risk. The apparent relationship with BMI at middle age and weight gain between age 30 years and diagnosis was eliminated by allowance for BMI at diagnosis. The age-related pattern of the association between BMI and breast cancer risk after menopause may reflect a duration-risk relationship, and resembles the effect of post-menopausal estrogen use, which seems greater among older women.

Glycemic index (GI) and glycemic load (GL) are measures of the metabolic effects of dietary carbohydrates. The higher their value, the greater the glucose and insulin responses. Raised insulin levels are associated with endometrial cancer and with its risk factors including obesity, diabetes and hypertension. To study the role of the GI and GL we analyzed the data of two hospital-based case-control studies on endometrial cancer conducted between 1988-98 in Italy and Switzerland, including a total of 410 women with incident, histologically confirmed endometrial cancer and 753 controls admitted for acute, non-neoplastic diseases. A food frequency questionnaire was used to assess the subjects usual diet and to derive estimates of dietary GI and GL. The odds ratios (OR) of endometrial cancer, after adjustment for major risk factors, for the highest versus the lowest quintile of dietary GI and GL were 2.1 (95% confidence interval [CI] = 1.4-3.2) and 2.7 (95% CI = 1.8-4.2), respectively. The associations were stronger in older women, in those with higher body mass index and in hormone replacement therapy users. Our study supports the hypothesis of a direct association between GI and endometrial cancer risk.

To provide further insight on the relationship between macronutrients and colorectal cancer, overall and by specific subsite(s), we carried out between 1992 and 1996 in 6 Italian areas a case-control study on 1,953 individuals of both sexes with incident colorectal cancer (age range 19-74) and 4,154 controls (age range 19-74) in hospital with acute, non-neoplastic diseases. A validated food-frequency questionnaire was used, including questions on 78 foods or recipes and on individual fat-intake pattern. The risk of cancer of the colon and rectum increased with total energy intake (odds ratio in highest vs. lowest quintile 1.43 and 1.50, respectively). The risk also rose significantly with an increase of starch intake, whereas it moderately decreased with an increase of protein intake. Monounsaturated fat intake appeared uninfluential, while saturated fat intake showed a modest direct association with rectal cancer. Polyunsaturated fat intake was inversely associated with colon cancer risk, particularly with the right colon.

We considered the association between diabetes and risk of endometrial cancer using data from a large case-control study conducted in Italy. Cases were 752 women with incident, histologically confirmed endometrial cancer < 75 years of age (median age 60 years, range 28-74) admitted to a network of hospitals in Milan. Controls were 2,606 patients (median age 54 years, range 25-74) aged < 75 years, admitted for acute non-neoplastic, non-gynecological, non-hormone-related conditions to the same network of hospitals where cases had been identified. A total of 132 (17.6%) cases and 116 controls (4.5%) reported a history of diabetes. The corresponding multivariate odds ratio (OR) was 2.9 [95% confidence interval (CI) 2.2-3.9]. No association emerged with diabetes diagnosed under age 40 (likely to be insulin-dependent diabetes), whereas the OR of endometrial cancer was 3.1 (95% CI 2.3-4.2) for diabetes diagnosed at age > or = 40 years. The OR of endometrial cancer in women with history of diabetes was 3.0 for women with a body mass index (BMI) (QI) kg/m2 < 25, 3.6 for those with a BMI of 25-29, and 3.3 for those with a BMI > or = 30. No consistent interaction or modifying effect was observed for any other covariate. Our results confirm that non-insulin-dependent diabetes is associated with the risk of endometrial cancer. The association may be mediated through elevated oestrogen levels in diabetic women, hyperinsulinemia or insulin-like growth factor-I (IGF-I).

Mortality data, abstracted from the World Health Organization database, are presented in tabular form for 26 cancer sites or groups of sites, plus total cancer mortality, in 36 European countries during the period 1995-1999. Trends in mortality are also given in graphic form for 23 major countries plus the European Union as a whole over the period 1960-1999. In the European Union, total cancer mortality declined by 7% for both sexes over the last 5 years considered. The fall since the late 1980s was 10% in both sexes, corresponding to the avoidance of over 90000 deaths per year, as compared to the rates of the late 1980s. For the first time, over the last few years, some leveling of mortality was reported also in the Russian Federation, the Czech Republic, Poland, Hungary and other Eastern European countries, although cancer rates in those areas remain exceedingly high. The overall favorable pattern of cancer mortality over recent years is largely driven by the decline of tobacco-related cancer mortality in men. However, important components of the trends are also the persistence of substantial falls in gastric cancer, mainly in Russia and Eastern Europe, the recent decline in intestinal cancer in both sexes and of breast cancer in women, together with the long-term falls in uterine (cervical) cancer, leukemias, Hodgkin's disease and other neoplasms amenable to advancements in diagnosis and treatment. Female lung cancer mortality has been declining in the Russian Federation, but is still rising in other areas of the continent. Thus, urgent intervention is needed to bring under control the tobacco-related lung cancer epidemic in European women before it reaches the high level observed in North America. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html

... Pordenone), Italy; I Clinica Ostetrico-Ginecologica, Università Degli Studi di Milano, Milan, Italy IJC25 10.1002/(SICI)1097-0215(19990702)82:1<151::AID-IJC25>3.0.CO;2-9 2 July 1999 1999 Carlo La Vecchia, Liliane Chatenoud, Silvia Franceschi, Maria Soler, Fabio Parazzini ...

The relation between post-menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case-control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non-neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1-9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer.

To investigate the relation between selected micronutrients and breast cancer risk, we conducted a case-control study of breast cancer between June 1991 and April 1994 in 6 Italian areas. The study included 2569 women admitted to the major teaching and general hospitals of the study areas with histologically confirmed incident breast cancer and 2588 control women with no history of cancer, who were admitted to hospitals in the same catchment areas for acute, non-neoplastic, nongynecological conditions unrelated to hormonal or digestive tract diseases or to long-term modifications of the diet. Dietary habits, including alcoholic beverage consumption, were investigated using a validated food frequency questionnaire, including 78 foods or food groups, several types of alcoholic beverages, some "fat intake pattern" questions and some open sections for foods consumed frequently by the subject and not reported in the questionnaire. To control for potential confounding factors, several multiple logistic regression models were used. When major correlates, energy intake and the mutual confounding effect of the various micronutrients were taken into account, beta-carotene, vitamin E and calcium showed a significant inverse association with breast cancer risk. The estimated odds ratios of the 5th quintile compared to the lowest one were 0.84 for beta-carotene, 0.75 for vitamin E and 0.81 for calcium. No significant association emerged for retinol, vitamin C, thiamin, riboflavin, iron and potassium. Our results suggest that a diet rich in several micronutrients, particularly beta-carotene, vitamin E and calcium, may be protective against breast cancer.

Flavonoids belong to a vast group of polyphenols widely distributed in all foods of plant origin. Because of their antioxidant, antimutagenic and antiproliferative properties, they have been hypothesized to contribute to the favorable effects of fruit and vegetables against cancer. The aim of this study is to investigate the relation of 6 classes of flavonoids (flavan-3-ols, flavanones, flavonols, flavones, anthocyanidins and isoflavones) with ovarian cancer risk, using data from a multicentric case-control study conducted in Italy between 1992 and 1999. The study included 1,031 cases with incident, histologically confirmed epithelial ovarian cancer and 2,411 controls admitted for acute, nonneoplastic conditions to major hospitals in the same catchment areas. In logistic regression models including study center, education, year of interview, parity, oral contraceptive use and family history of ovarian or breast cancer or both, an inverse relation with significant trend in risk was found between ovarian cancer and flavonols [odds ratio (OR), 0.63; 95% confidence intervals (CI) 0.47-0.84] as well as isoflavones (OR, 0.51; 95% CI, 0.37-0.69), comparing the highest versus the lowest quintile. Further adjustment for fruit and vegetable intake did not modify these associations, suggesting that isoflavones and flavonols may have a distinct role in explaining the effect of fruit and vegetable against ovarian cancer. On the basis of our findings and the relevant literature, we infer that isoflavones, and perhaps flavonols, may have favorable effects with respect to ovarian cancer risk.

Various studies have reported an inverse relation between oral contraceptive (OC) use and the risk of colorectal cancer, but the issue is still open. In order to quantify the association between OC use and colorectal cancer risk, we performed a systematic review and meta-analysis of studies on this issue. We identified all relevant studies published, in English, as original articles up to December 2008 through a search of the literature using PubMed and EMBASE, and by reviewing the references from the retrieved articles. The summary relative risk of colorectal cancer for ever versus never OC use was 0.82 (95% confidence interval, CI, 0.69-0.97) from 11 case-control studies, 0.81 (95% CI, 0.75-0.89) from seven cohort studies, and 0.81 (95% CI, 0.72-0.92) from all studies combined. The results were similar for colon and rectal cancer. No difference was evident according to duration of OC use both for colon and rectal cancer, although there is an indication that the protection is stronger for more recent use (OR = 0.70, 95% CI, 0.53-0.90, on the basis of four studies). Epidemiological data consistently indicate that OC users have a reduced risk of colorectal cancer, and that the protection is greater for recent use in the absence, however, of a duration-risk relation.

Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta-analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case-control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non-drinkers was 0.54 (95% confidence interval [CI] 0.38-0.76) for case-control studies and 0.64 (95% CI 0.56-0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49-0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57-0.85), and that for high drinkers was 0.45 (95% CI 0.38-0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72-0.83) from case-control studies, 0.75 (95% CI 0.65-0.85) from cohort studies, and 0.77 (95% CI 0.72-0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion.

While parity is a protective factor in ovarian cancer, the role of time factors of pregnancy and birth is still controversial. We considered therefore the role of birth timing in the risk in ovarian cancer from a large case-control study. Cases were 971 women (age range 22-74 years, median age 54) with histologically confirmed, incident epithelial ovarian cancer, interviewed between 1983 and 1991 in a network of hospitals in Milan, Italy. Controls were 2758 women (age range 23-74 years, median age 52) admitted to the same hospitals where cases were identified for acute, nonneoplastic conditions. In comparison with nulliparous women, the multivariate odds ratios (OR) were 0.8 for women reporting one or two and 0.6 for those with three or more births. No clear association emerged between time since last birth and ovarian cancer. Compared to women who had last given birth since > or =20 years, a moderately increased risk of ovarian cancer was observed in the first 10 years after last birth, with an OR of 1.7 (95% confidence interval, CI 1.0-2.9). When we considered only multiparous women and included in the multivariate analysis allowance for age at first birth, the OR decreased to 1.2 (95% CI 0.6-2.4). No consistent pattern of trends was observed > or =10 years since last pregnancy. This study confirms the protective effect of parity on ovarian carcinogenesis, but shows no consistent pattern of risk across time since last birth.

Trends in ovarian cancer mortality over the period 1955-1989 were analyzed for 25 European countries (excluding the Soviet Union and a few small countries) on the basis of the official death certification data from the World Health Organization database. The overall variation in age-standardized ovarian cancer mortality at all ages declined appreciably, from over 17-fold during the period 1955-1959 (i.e., between 10.5/100,000 in Denmark and 0.6/100,000 in Spain, world standard) to 3.4-fold (i.e., between 9.9/100,000 in Denmark and 2.9/100,000 in Spain) in the late 1980s. When a comparison was made between the late 1950s and the 1980s, ovarian cancer mortality increased in most European countries, except Denmark, Sweden, and Switzerland, where certified mortality was already elevated in the late 1950s, although also in these countries the peak rate around or over 10/100,000 was reached during the 1960s. However, when the changes over the last decade were considered, ovarian cancer mortality trends were downward in all Nordic countries, Germany, Switzerland, Austria, and Czechoslovakia. Mortality was rising somewhat, though to a smaller extent, in Ireland, Britain, and Southern Europe. Trends were more favorable in middle-aged women (35 to 64 years), and, to an even greater extent, in young women (aged 20 to 44), among whom substantial declines, particularly over the last decade, were observed in most European countries, approaching 50% in Britain and Scandinavia. These trends are discussed in terms of changes in risk factor exposure (i.e., trends in average parity and oral contraceptive use), diagnostic and therapeutic improvements, ovariectomy, and changes in case ascertainment and certification.

Breastfeeding has been inversely related to the risk of ovarian cancer, but results from published studies are inconsistent. In order to provide further information, we analyzed data from a large case-control study conducted in four Italian areas. Cases were 1031 women with epithelial ovarian cancer. Controls were 2411 women admitted to the same network of hospitals for a wide spectrum of acute non-neoplastic conditions, unrelated to known risk factors for ovarian cancer. There were inverse trends in risk with increasing duration of breastfeeding and number of children breastfed, but when parity and several other potential confounding factors were taken into account, no residual association was evident (odds ratio = 1.21 for 17 or more months of breastfeeding and 0.90 for those who had breastfed 4 or more children, as compared to women who had never breastfed). This study showed an inverse relation between breastfeeding and ovarian cancer risk, which however was accounted for by parity. The analyses by histologic subtypes suggested that a role of breastfeeding would be larger for serous neoplasms in the absence, however, of significant heterogeneity.

The relationship between fertility drug use and risk of borderline ovarian cancer has been analyzed using data from a case-control study. Cases were 93 women aged 23 to 64 years with histologically confirmed diagnosis of borderline ovarian tumor (according to the World Health Organization criteria) who were admitted to the Obstetrics and Gynecology Clinics of the University of Milan. Control subjects were 273 women (ages 24-64 years) admitted for acute nongynecological, nonhormonal, and nonneoplastic conditions. Four cases (4.3%) and no control reported fertility drugs use: this difference was statistically significant (Fisher's exact test P = 0.004).

Carotenoids may reduce the risk of coronary heart disease through their antioxidant properties, but the results of epidemiological studies are controversial. We analysed the relation between the intake of selected carotenoids and retinol and risk of acute myocardial infarction (AMI). A case-control study was conducted in Milan, Italy, in 1995-2003. Cases were 760 patients with nonfatal AMI, and controls 682 patients admitted to hospital. The risk of AMI decreased with increasing intake of alpha-carotene (odds ratios, OR = 0.71, 95% confidence intervals, CI 0.51-0.98, for the highest vs the lowest quartile of intake), beta-carotene (OR = 0.71, 95% CI 0.50-1.01) and beta-criptoxanthin (OR = 0.64, 95% CI 0.46-0.88). No associations emerged for total carotenoids, lycopene, lutein plus zeaxanthin and retinol. Our study suggests a weak protective effect of alpha-carotene, beta-carotene and beta-criptoxanthin on the risk of AMI. It also indicates that total carotenoids, lycopene, lutein plus zeaxanthin and retinol were not related to the risk of the disease.

Acetaldehyde is a naturally-occurring carcinogenic compound, present in different food items, especially in alcoholic beverages. The aims of this study were to measure acetaldehyde concentration in different beverages consumed in Italy and to estimate the potential cancer risk. The analytical procedure was based on headspace solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS), using the isotopic dilution method. The margin of exposure (MOE) approach of the European Food Safety Authority (EFSA) was used for risk characterisation. The highest concentrations (median, min-max) were detected in grappa samples (499, 23.4-1850mg/l), followed by fruit-based liqueurs and spirits (62.0, 5.23-483mg/l) and wine (68.0, 18.1-477mg/l); the lowest were detected in gin (0.91, 0.78-1.90mg/l). The lowest MOE was estimated for high wine consumers (69). These results suggest that regulatory measures and consumer guidance may be necessary for acetaldehyde in beverages.

A number of co-aggregations of cancers at different sites has been reported, including recognized syndromes (e.g., Li-Fraumeni), and aggregations between cancers at breast, stomach and ovary, between cancers at prostate, urinary tract and other sites, as well as between several tobacco-related neoplasms. In a network of case-control studies from Italy and Switzerland, including more than 12,000 cases of 13 different cancers, after controlling for multiple testing, significant associations emerged between oral and pharyngeal cancer and family history of laryngeal cancer (relative risk (RR): 3.3); esophageal cancer and family history of oral and pharyngeal cancer RR: 4.1; breast cancer and family history of colorectal cancer (RR: 1.5) and of hemolymphopoietic cancers (RR: 1.7); ovarian cancer and family history of breast cancer (RR: 2.3); and prostate cancer and family history of bladder cancer (RR: 3.4). Shared exposures to environmental factors within families account for some of the observed aggregations, together with heritable, and hence, genetic factors.

We investigated the relation between diabetes and the risk of prostate cancer, as epidemiological results are controversial. A hospital-based case-control study was conducted in Italy between 1991 and 2002. Cases were 1294 men, aged <75 years, with incident histologically confirmed prostate cancer, and controls were 1451 men, aged <75 years, admitted to hospital for acute non-neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. No material association between diabetes and prostate cancer was observed, with a multivariate OR of 1.02 (95%CI 0.75-1.40). Prostate cancer was not related to time since diagnosis of diabetes (OR 0.82 and 0.97 for <5 and >/=15 years since diagnosis respectively). The OR were respectively 1.63 (95%CI 0.70-3.81) and 0.96 (95%CI 0.68-1.34) in men diagnosed with diabetes at age <45 or >/=45 years. The risk estimates were similar across strata of age at interview, body mass index and, among cases, of Gleason score. This study shows no material association between diabetes and prostate cancer risk.

A relation of prostate cancer risk with calcium, vitamin D and phosphorus has been suggested, but remains controversial. A case-control study was conducted in Italy in 1991-2002. Cases were 1294 men with incident prostate cancer, and controls were 1451 men admitted to hospital for acute non-neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression. Compared to the lowest one quintile of dietary calcium intake the OR was 1.18 for the highest, 1.01 for an increment of 622 mg/day of calcium, and 1.29 (95% CI 0.78-2.13) for 2000 mg/day or more of calcium. The OR of prostate cancer for the highest quintile of dietary intake of vitamin D and phosphorus were 1.33 and 1.20 respectively. This study shows no material association of dietary intake of calcium, vitamin D and phosphorus with prostate cancer risk.

To investigate the association between fiber intake and risk of acute myocardial infarction (AMI), also according to type and source of fiber, in a Mediterranean country. Hospital-based case-control study. Northern Italy. A total of 507 cases of first nonfatal AMI and 478 controls in hospital for acute conditions. Subjects were interviewed with a questionnaire that included a validated food frequency section. Odds ratios (OR) were obtained using multiple logistic regression, and adjusted for several recognized risk factors for AMI. Fiber was measured as non-starch polysaccharides. Compared with the lowest one, the OR in the highest tertile was 0.72 for total fiber, 0.64 for soluble fiber, 0.77 for total insoluble fiber, 0.71 for cellulose, 0.81 for insoluble non-cellulosic polysaccharides, 0.82 for vegetable fiber, 0.64 for fruit fiber and 1.11 for cereal fiber, and the estimates were statistically significant for soluble and fruit fiber. When further adjusted for beta-carotene, vitamin C and vitamin E intake, the fruit fiber still showed the strongest inverse relation, although the association was no longer significant. The protective effect of fiber was more marked in, or restricted to, subjects with other AMI risk factors, such as smokers, diabetics and hypertensives. Though an inverse association between fiber intake and AMI risk appears established, the causality of this association is still open to debate. In this population, cereal fiber derives chiefly from refined grains, and this may explain the lack of protection by this type of fiber.

To update trends in mortality from coronary heart diseases (CHD) and cerebrovascular diseases (CVD) over the period 1981-2004 in Europe, the USA, Latin America, Japan and other selected areas of the world. Age-standardized mortality rates were derived from the World Health Organization database. Joinpoint analysis was used to identify significant changes in trends. In the European Union (27 countries), CHD mortality in men declined from 139/100,000 in 1985-1989 to 93/100,000 in 2000-2004 (-33%). In women, the fall was from 61/100,000 to 44/100,000 (-27%). In this area, a decline by over 30% was also registered in CVD mortality for both sexes. In the Russian Federation and other countries of the former Soviet Union, CHD rates in 2000-2004 were exceedingly high, around 380/100,000 men and 170/100,000 women in Russia, 430 for men and 240 for women in Ukraine, 420 and 200 in Belarus. For CVD, a similar situation was registered, with mortality rates of 226/100,000 for men and 159/100,000 for women in 2004 in the Russian Federation, and more than 24% increase since the late 1980s for men and 15% for women. CHD and CVD mortality continued to decline in most Latin American countries, Australia and other areas considered, including Asia (even if with marked differences). Although mortality from CHD and CVD continues to decline in several areas of the world including most countries of Europe and of the America providing data and Australia, unfavourable trends were still observed in the Russian Federation and other countries of the former Soviet Union, whose recent rates remain exceedingly high.

Controversial information is available with reference to the role of type or yield of cigarettes on the risk of cardiovascular disease. We considered the issue in a combined dataset of three case-control studies of acute myocardial infarction conducted in Italy between 1983 and 2003. Cases were 1990 subjects with a first episode of non-fatal acute myocardial infarction, and controls were 2521 patients in hospital for acute diseases unrelated to smoking or other recognized risk factors for myocardial infarction. The odds ratio and the corresponding 95% confidence interval (CI) were derived by unconditional multiple logistic regression models, including terms for age, sex, and several major risk factors for myocardial infarction. As compared to never smokers, the multivariate odds ratio was 2.70 (95% CI 2.01-3.63) for smokers of low tar cigarettes (<10 mg), 3.06 (95% CI 2.53-3.70) for intermediate (10-19 mg) and 3.14 (95% CI 2.12-4.64) for high tar yield (> or =20 mg). After further allowance for duration of smoking and number of cigarettes per day, as compared to low tar yield cigarettes, the odds ratio was 1.14 (95% CI 0.85-1.53) for intermediate, and 1.28 (95% CI 0.81-2.02) for high tar yield. Our study confirms that no substantial reduction in acute myocardial infarction risk resulted from the decrease of cigarette tar yield.

The objective of this study is to investigate the effect of menstrual and reproductive variables, breastfeeding, exogenous hormones, and gynecological conditions on endometrial cancer risk. We conducted a case-control study in Italy, including 454 women with endometrial cancer and 908 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Endometrial cancer risk was inversely associated with age at menarche (OR = 0.7, 95% CI = 0.5-1.0, for > or =14 vs. <12 years), and directly associated with age at menopause (OR = 1.8, 95% CI = 1.1-2.7, for > or =55 vs. <50 years) and years of menstruation (OR = 2.4, 95% CI = 1.7-3.4, for highest vs. lowest tertile). Multiparity strongly reduced the risk among women under 60 years of age (OR = 0.3, 95% CI = 0.2-0.6, for > or =3 deliveries vs. <2). Oral contraceptive use conferred a 40% reduced risk (95% CI = 0.4-1.0), irrespective of time since cessation. Although based on small numbers, women with a history of treated infertility (OR = 2.7, 95% CI = 1.1-6.4) or endometriosis (OR = 4.0, 95% CI = 1.0-15.5) were at increased risks. No significant associations with endometrial cancer risk emerged for age at first/last birth, breastfeeding, menopausal status, hormone replacement therapy, and history of uterine fibromyomas or polycystic ovary. In conclusion, this study confirms the importance of multiparity, years of menstruation, and oral contraceptive use in endometrial cancer etiology, thus contributing to identify women at elevated risk of such neoplasm.

Trends in mortality from breast cancer over the period 1970-2000 were analysed for 38 European countries and the European Union (EU). Age-standardized mortality rates were computed by the direct method, and joinpoint analysis was used to identify significant changes in rates. A favourable pattern in breast cancer mortality in the 25 countries of the EU (as defined in May 2004) was observed after 1989, leading to a fall in overall rates from 21.3/100,000 in 1990 to 18.9 in 2000. The annual percentage change in the EU was -2.1% between 1995 and 2000. Most northern European countries, including several Scandinavian countries and the UK, but also some central and southern European countries like Germany, Poland, the Czech Republic, Austria, Switzerland, Italy and Spain showed appreciable falls in rates (i.e. between 8 and 19% in the last 5 calendar years). The declines were larger below age 50, approaching 20% in several countries. The falls were smaller in France, Greece, Portugal and most eastern European countries. In the Russian Federation, all-age breast cancer mortality increased from 16.1 to 17.3/100,000 (+7.5% over the last 5 calendar years). These patterns reflect converging trends in breast cancer rates across Europe, which can be related to the more uniform reproductive and lifestyle habits. The fall in breast cancer mortality observed in most European countries over the last decade has to be attributed to earlier detection and improved treatment, although the definite reasons for the different trends in various countries remain at least in part unclear.

Scanty information, limited to selected areas of the country, is available on cancer mortality in Brazil. Age-standardized (world population) mortality rates between 1980 and 2004, derived from the WHO database, were computed for all cancers and 24 major cancer sites in Brazil. Joinpoint regression analyses were used to identify the significant changes in trends and estimate annual percent change (APC) in rates. Total cancer mortality rates increased over the last decade in men (APC = 0.5) to reach 101.2/100 000, and in women (APC = 0.3) to reach 71.3/100 000. In men, upward trends were observed for cancers of the oral cavity and pharynx with a rate of 5.9/100 000 in 2000-2004, intestines (whose rate, however was low, i.e. 7.6), prostate (12.2), and leukemias (3.4). Male lung cancer increased until 1993 (APC = 1.39) and decreased thereafter (APC = -0.29), with a relatively low rate of 16.2/100 000 in 2000-2004. In women, there were steady upward trends for cancers of the lung (APC = 2.3), reaching 6.2/100 000 in 2000-2004, and leukemias (2.5). Breast cancer mortality leveled off at around 10/100 000 in the last decade, whereas declines were observed for cancers of the uterus, whose rate (8.3) however, remained comparatively high. Declines were observed for stomach cancer in both sexes, with rates of 11.1 in men and 4.6 in women. In conclusion, the key issues of cancer mortality in Brazil are the high rates of head and neck cancers in men and (cervix) uterine cancer in women, that is, in principle cancers that are largely avoidable through prevention, screening, and early diagnosis.

To investigate the relationship between family history of cancer in first-degree relatives and the risk of endometrial cancer, we carried out a large multicentre case-control study in Italy between 1992 and 2006, including 454 endometrial cancer cases and 908 controls admitted in hospital for acute, non-neoplastic diseases. Conditional logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI). Relative to women with no family history of uterine cancer, the ORs were 2.1 (95% CI: 0.7-6.4) for those reporting a family history of endometrial cancer and 1.8 (95% CI: 1.0-3.2) for a family history of any uterine cancer. A family history of intestinal cancer was directly associated with endometrial cancer risk (OR=1.6; 95% CI: 1.0-2.7). Direct associations were found for a few other cancer sites. In conclusion, a family history of endometrial, uterine or intestinal cancer in first-degree relatives is associated with an increased risk of endometrial cancer.

The two main determinants of oral and oesophageal cancer in Europe are alcohol and tobacco, and the two cancer sites show several similarities in their descriptive epidemiology. This study compares mortality from cancers of the oral cavity and oesophagus in European countries to evaluate similarities and differences. From official death certification numbers and population estimates, we obtained age-standardized rates for all ages and truncated (35-64 years). In most countries, rates for men tended to increase between 1955-59 and 1990-92 for both sites, although the increases were more marked for oral cancer. In the UK and Ireland, however, oral cancer decreased and oesophageal cancer increased, while in Finland and Iceland mortality for both sites decreased. The most striking increases were in Hungary, where the truncated rate in most recent calendar periods reached the highest levels in Europe. In France, rates for both cancers were extremely high: oral cancer increased from 1955-59 to the early 1980s, but started to decline afterwards. Mortality rates were much lower for women than men, and the correlation between the two sites was less marked. An age, period and cohort model, applied to the rates for men in selected European countries, suggested strong cohort effects for both cancers, generally more marked for oral cancer, with substantial increases in the cohorts born after 1920. The mortality rates of cancers of the oral cavity and oesophagus show several analogies, as expected from their relation to tobacco and alcohol; but some discrepancies suggest that other, less well-identified, factors may also influence their rates and trends in Europe.

In order to assess the comparability and reproducibility of information from a questionnaire used in a case-control study on digestive tract cancers conducted in Italy, a total of 400 subjects were randomly selected from a large sample of hospital controls and contacted at home to repeat the interview. Of these, 294 (73%) subjects were re-interviewed. Mean values of intake were computed for the 400 subjects selected, and among the 294 responders for the first and second interview. These values were comparable, most of them being within a 10% range. Spectrum correlation coefficient (rs) values of consumption between the first and second interview were > 0.65 for consumption of pastries, pasta or rice, bread, fish, milk, green vegetables, eggs and apples; between 0.50 and 0.65 for meat, chicken, liver, ham, cold cuts, cheese, fruit, cabbage, carrots, tomatoes, peppers, salad, citrus fruit and melon; and lower than 0.50 for a few infrequently eaten foods. For all foods, the estimated average weekly intake in the second interview increased consistently and substantially with increasing tertile of the first interview. This study shows a satisfactory comparability of dietary information from subjects interviewed at home with that provided during their original interview in the hospital, and a good reproducibility of information collected in the two settings.

The knowledge of major sources of macro- and micronutrients is essential in order to interpret differences in the diet-cancer link in various geographical areas and to provide better nutritional guidelines. For this purpose we took advantage of the control group of a case-control study on breast cancer carried out in six Italian areas. The dietary habits of 2,588 cancer-free women aged 20-74 years (median age 56) were elicited between 1991 and 1994 by means of an interviewer-administered food frequency questionnaire (FFQ) that included 78 foods or food groups, in addition to several questions on general dietary pattern (e.g., fat in seasoning). Bread was the first contributor for total energy (12%), protein (8%) and starch (32%) intake, whereas, for saturated fatty acid, the first sources were different types of cheese (28%); for monounsaturated fatty acids the dressing oils of salad and tomatoes (12%); and, for sugars, apples and pears (19%). Raw vegetables and fresh fruit represented the most important source of most vitamins. The first contributors of vitamin C and beta-carotene were citrus fruits (29%) and raw carrots (17%), respectively. Thus, between 40 and 80% of specific macronutrient intake and up to 90% intake of several micronutrients were derived from the first ten foods or food groups. Often, the major contributors to the intake of a specific component were foods with a relatively low content, but eaten in large quantities. This work further highlights the specificity of nutrient sources in southern European populations.

Data on the role of aspirin on endometrial cancer risk are scanty. Here we provide additional information on the issue, using data from a multicentric Italian case-control study. The study was conducted between 1992 and 2006 in three Italian areas, on 442 cases with histologically confirmed endometrial cancer and 676 control women admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic, non-gynaecological, non-hormone-related conditions, providing information on aspirin use. Odds ratios (OR) of endometrial cancer and corresponding 95% confidence intervals were calculated using multiple logistic regression models, including terms for sociodemographic characteristics, body mass index and hormonal and reproductive factors. Regular aspirin use was reported by 28 (6.3%) cases and 46 (6.8%) controls, corresponding to a multivariate OR of 0.65 (95% confidence interval 0.37-1.11). There was no consistent pattern of risk with duration of use, nor with age at first use, time since first use or time since last use. Further, there was no difference in risk estimates across strata of body mass index. This study--the first one from a population outside North America--adds relevant information on the absence of a consistent association between aspirin use and endometrial cancer risk, even in high-risk overweight and obese women.