Modelling body mass index and endometrial cancer risk in a pooled-analysis of three case-control studies.

OBJECTIVE: To quantify the relation between body mass index (BMI) and endometrial cancer risk, and to describe the shape of such a relation. DESIGN: Pooled analysis of three hospital-based case-control studies. SETTING: Italy and Switzerland. POPULATION: A total of 1449 women with endometrial cancer and 3811 controls. METHODS: Multivariate odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from logistic regression models. The shape of the relation was determined using a class of flexible regression models. MAIN OUTCOME MEASURE: The relation of BMI with endometrial cancer. RESULTS: Compared with women with BMI 18.5 to <25 kg/m(2) , the odds ratio was 5.73 (95% CI 4.28-7.68) for women with a BMI ≥35 kg/m(2) . The odds ratios were 1.10 (95% CI 1.09-1.12) and 1.63 (95% CI 1.52-1.75) respectively for an increment of BMI of 1 and 5 units. The relation was stronger in never-users of oral contraceptives (OR 3.35, 95% CI 2.78-4.03, for BMI ≥30 versus <25 kg/m(2) ) than in users (OR 1.22, 95% CI 0.56-2.67), and in women with diabetes (OR 8.10, 95% CI 4.10-16.01, for BMI ≥30 versus <25 kg/m(2) ) than in those without diabetes (OR 2.95, 95% CI 2.44-3.56). The relation was best fitted by a cubic model, although after the exclusion of the 5% upper and lower tails, it was best fitted by a linear model. CONCLUSIONS: The results of this study confirm a role of elevated BMI in the aetiology of endometrial cancer and suggest that the risk in obese women increases in a cubic nonlinear fashion. The relation was stronger in never-users of oral contraceptives and in women with diabetes.

Mediterranean diet and risk of endometrial cancer: a pooled analysis of three Italian case-control studies.

BACKGROUND: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. METHODS: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. RESULTS: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. CONCLUSIONS: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Diabetes mellitus and the risk of bladder cancer: an Italian case­control study.

BACKGROUND: Diabetes mellitus has been associated with an increased risk of bladder cancer, although the evidence is still open to discussion. METHODS: We examined this association using data from a multicentre Italian case­control study, conducted between 2003 and 2014 on 690 bladder cancer cases and 665 frequency-matched hospital controls. Odds ratios (ORs) for diabetes were estimated by unconditional multiple logistic regression models, after allowance for major known risk factors for bladder cancer. RESULTS: One hundred and twelve (16.2%) cases and 57 (8.6%) controls reported a diagnosis of diabetes mellitus, corresponding to a multivariate OR of 2.09 (95% confidence interval (CI): 1.46­3.01). Bladder cancer risk increased with duration of diabetes (OR 1.92 for 1­ <5 years, 1.63 for 5­ <10 years, 2.39 for 10­ <15 years, and 2.58 for ≥15 years). The increased risk of bladder cancer was consistent in strata of age and education, whereas it was somewhat lower (although not significantly) in women (OR 1.18), in never (OR 1.31) and current (OR 1.42) smokers, and in subjects with a body mass index <25 kg m(-2) (OR 1.48). CONCLUSION: The present study provides further support of a role of diabetes in bladder cancer aetiology, although some residual confounding by tobacco, body mass index, or other unmeasured covariates may partly explain the association observed.

Dietary non-enzymatic antioxidant capacity and the risk of myocardial infarction: a case-control study in Italy.

BACKGROUND AND AIMS: Oxidative processes have been related to atherosclerosis, but there is scanty information on the role of dietary antioxidants in the prevention of acute myocardial infarction (AMI). METHODS AND RESULTS: The relationship between non-enzymatic antioxidant capacity (NEAC) and the risk of nonfatal AMI was investigated in a case-control study conducted in Milan, Italy, between 1995 and 2003. Cases were 760 patients below 75 years with a first episode of AMI and controls were 682 patients admitted to hospitals for acute conditions, who completed an interviewer-administered food frequency questionnaire, tested for validity and reproducibility. NEAC (excluding coffee) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). The odds ratios (OR) of AMI, and the corresponding 95% confidence intervals (CI), were obtained by multiple logistic regression models including terms for main risk factors of AMI and total energy intake. NEAC was inversely related with the risk of AMI. The ORs for the highest quintile compared with the lowest one were 0.41 (95% CI, 0.27-0.63) for FRAP, 0.42 (95% CI, 0.27-0.65) for TEAC and 0.41 (95% CI, 0.27-0.62) for TRAP, with significant trends in risk. The inverse relationship was apparently stronger in women and in subjects aged ≥ 60 years. CONCLUSIONS: Our results support a favorable role of dietary NEAC in the prevention of AMI, and encourage a high consumption of fruit and vegetables and a moderate consumption of wine and whole cereals.

Dietary folates and cancer risk in a network of case-control studies.

BACKGROUND: Folate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers. PATIENTS AND METHODS: The study is based on a network of case-control studies conducted in Italy and Switzerland in 1991-2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors. RESULTS: For a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 µg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking. CONCLUSIONS: Our data support a real inverse association of dietary folate intake with the risk of several common cancers.

History of cholelithiasis and cancer risk in a network of case-control studies.

BACKGROUND: We analyzed the relationship between cholelithiasis and cancer risk in a network of case-control studies conducted in Italy and Switzerland in 1982-2009. METHODS: The analyses included 1997 oropharyngeal, 917 esophageal, 999 gastric, 23 small intestinal, 3726 colorectal, 684 liver, 688 pancreatic, 1240 laryngeal, 6447 breast, 1458 endometrial, 2002 ovarian, 1582 prostate, 1125 renal cell, 741 bladder cancers, and 21 284 controls. The odds ratios (ORs) were estimated by multiple logistic regression models. RESULTS: The ORs for subjects with history of cholelithiasis compared with those without were significantly elevated for small intestinal (OR=3.96), prostate (OR=1.36), and kidney cancers (OR=1.57). These positive associations were observed ≥10 years after diagnosis of cholelithiasis and were consistent across strata of age, sex, and body mass index. No relation was found with the other selected cancers. A meta-analysis including this and three other studies on the relation of cholelithiasis with small intestinal cancer gave a pooled relative risk of 2.35 [95% confidence interval (CI) 1.82-3.03]. CONCLUSION: In subjects with cholelithiasis, we showed an appreciably increased risk of small intestinal cancer and suggested a moderate increased risk of prostate and kidney cancers. We found no material association with the other cancers considered.

A meta-analysis of coffee consumption and pancreatic cancer.

BACKGROUND: Since when in 1981 a case-control study showed a positive association between coffee and pancreatic cancer, several studies reported inconsistent results on this issue. MATERIALS AND METHODS: We conducted a systematic bibliography search updated March 2011 to identify observational studies providing quantitative estimates for pancreatic cancer risk in relation to coffee consumption. We used a meta-analytic approach to estimate overall relative risk (RR) and 95% confidence interval (CI) for the highest versus the lowest coffee consumption categories, using random-effects models. RESULTS: Based on 37 case-control and 17 cohort studies (10,594 cases), the pooled RR for the highest versus lowest intake was 1.13 (95% CI 0.99-1.29). Considering only the smoking-adjusting studies, the pooled RRs were 1.10 (95% CI 0.92-1.31) for the 22 case-control, 1.04 (95% CI 0.80-1.36) for the 15 cohort, and 1.08 (95% CI 0.94-1.25) for all studies. The pooled RR for the increment of one cup of coffee per day was 1.03 (95% CI 0.99-1.06) for the 28 smoking-adjusting studies reporting three or more coffee consumption categories. No significant heterogeneity was observed across strata of study design, sex, geographic region, and other selected characteristics. CONCLUSIONS: This meta-analysis provides quantitative evidence that coffee consumption is not appreciably related to pancreatic cancer risk, even at high intakes.

Anthropometric measures at different ages and endometrial cancer risk.

BACKGROUND: Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain. METHODS: A case-control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models. RESULTS: The OR for BMI >30 at diagnosis compared with 20 to <25 kg m(-2) was 4.08 (95% CI: 2.90-5.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR (2.10; 95% CI: 1.43-3.09) in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women (OR=1.60; 95% CI: 0.52-4.96). CONCLUSION: The predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age.

Coffee and cancers of the upper digestive and respiratory tracts: meta-analyses of observational studies.

BACKGROUND: Data of epidemiological studies on the relation between coffee drinking and upper aerodigestive tract cancer risk are scattered and inconclusive. We therefore conducted systematic meta-analyses of observational studies published before October 2009. MATERIALS AND METHODS: We combined relative risks (RR) with 95% confidence intervals (CI) for cancers of the oral cavity/pharynx (OP) and larynx, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), comparing the highest versus the lowest categories of coffee consumption, using random-effects models. RESULTS: For OP cancer, the pooled RR was 0.64 (95% CI 0.51-0.80) for highest versus lowest coffee drinking, based on a total of 2633 cases from one cohort and eight case-control studies, with no significant heterogeneity across studies. The RRs were 0.61 (95% CI 0.41-0.89) for European, 0.58 (95% CI 0.36-0.94) for American and 0.74 (95% CI 0.48-1.15) for Asian studies, where coffee consumption is lower. The corresponding RRs were 1.56 (95% CI 0.60-4.02) for laryngeal cancer (732 cases from three case-control studies), 0.87 (95% CI 0.65-1.17) for ESCC (2115 cases from one cohort and six case-control studies) and 1.18 (95% CI 0.81-1.71) for EAC (415 cases from three case-control studies). CONCLUSION: Coffee drinking is inversely related to OP cancer risk, while there is no relation with laryngeal cancer, ESCC and EAC.

Macronutrients, fatty acids and cholesterol intake and stomach cancer risk.

BACKGROUND: Several case-control studies have examined the association between intake of selected macronutrients and stomach cancer, with inconsistent results regarding total energy, proteins, carbohydrates and fats. MATERIALS AND METHODS: We considered the relation between total energy, various macronutrients and fatty acids and gastric cancer using data from a case-control study conducted in northern Italy. Cases were 230 patients with incident, histologically confirmed stomach cancer. Controls were 547 frequency-matched patients, admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. Logistic regression models conditioned on age and sex and adjusted for selected covariates were used to estimate the odds ratios (ORs) of stomach cancer. RESULTS: The multivariate ORs were 0.65 [95% confidence interval (CI) 0.43-0.98] for the highest versus lowest tertile of vegetable fats and 0.66 (95% CI 0.44-0.97) for polyunsaturated fatty acids. No significant association was found for proteins, sugars, starch, total and animal fats, saturated and monounsaturated fatty acids and cholesterol. CONCLUSION: In conclusion, our study indicates that selected vegetable fats have a favorable effect on stomach cancer risk.

Dietary intake of selected micronutrients and gastric cancer risk: an Italian case-control study.

BACKGROUND: A high consumption of non-starchy vegetables and fruits likely decreases the risk of gastric cancer, but no specific constituent of plant foods has been consistently identified to explain this association. PATIENTS AND METHODS: We considered several micronutrients and minerals in an Italian case-control study conducted between 1997 and 2007, including 230 patients with incident, histologically confirmed gastric cancer and 547 matched controls, admitted with acute conditions. Micronutrients computation was based on a validated and reproducible food frequency questionnaire, through an Italian food composition database. We estimated odds ratios (ORs) using conditional logistic regression, adjusted for energy intake and selected covariates. RESULTS: We found decreased ORs for the highest versus lowest quartile of vitamin E (OR=0.50), alpha-carotene (OR=0.52) and beta-carotene (OR=0.42) intake. Gastric cancer was directly associated with sodium, with ORs of 2.22 for the second, 2.56 for the third and 2.46 for the fourth quartile of intake. No significant relation emerged with iron, calcium, potassium, zinc, vitamin C, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin D, retinol, beta-cryptoxanthin, lycopene and lutein plus zeaxanthin. CONCLUSIONS: Our data support a favourable effect on gastric cancer of vitamin E and selected carotenoids and a detrimental effect of sodium even at intermediate levels of intake.

Macronutrients, fatty acids and cholesterol intake and endometrial cancer.

BACKGROUND: There is some evidence that dietary habits may influence the risk of endometrial cancer independently of body mass, although the role of diet on endometrial carcinogenesis is unclear. PATIENTS AND METHODS: We carried out a multicenter case-control study from 1992 to 2006 in Italy on 454 women with incident, histologically confirmed endometrial cancer (age range 18-79 years) and 908 controls (age range 19-79 years) admitted to hospitals for acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate macronutrients, fatty acids and cholesterol intake. Logistic regression models, conditioned on age and study centre, and adjusted for major known risk factor of endometrial cancer and residual of energy intake were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Significant direct associations were observed with intake of energy (OR = 1.7 for the highest versus the lowest quintile, 95% CI = 1.1-2.5), and cholesterol (OR = 2.1, 95% CI = 1.4-3.2), while a direct borderline association emerged with saturated fatty acids (OR = 1.3, 95% CI = 0.9-2.0). There was no association with proteins, sugars, starch, total fat and other selected fatty acids. CONCLUSION: Energy and cholesterol intake were associated with endometrial cancer.

History of treated hypertension and diabetes mellitus and risk of renal cell cancer.

BACKGROUND: An increased risk of renal cell cancer (RCC) has been reported in subjects with hypertension. Whether this association may vary according to sex, smoking, obesity, or RCC clinical presentation is unclear. Results on the link between diabetes mellitus and RCC are inconclusive. PATIENTS AND METHODS: We conducted an Italian multicenter case-control study, including 767 (494 men, 273 women) incident cases of RCC, under 80 years of age, and 1534 hospital controls, frequency-matched to cases. Multiple logistic regression models, conditioned to center, sex, and age, and adjusted for period of interview, education, smoking, and body mass were used to estimate odds ratios (OR). RESULTS: Compared with subjects never treated, patients with a history of treated hypertension [OR = 1.7, 95% confidence interval (CI) 1.4-2.1] reported an excess risk of RCC. This pattern was confirmed in different strata of sex, education, smoking habits, body mass, tumor histological type, stage, or grade. The attributable risk of RCC for treated hypertension in this population was 16%. A slight, nonsignificant increased risk was found for history of diabetes mellitus (OR = 1.3, 95% CI 0.9-1.7). CONCLUSION: A possible causal role of hypertension in renal cell carcinogenesis is supported by the consistency of the direct association.

Consumption of sweet foods and breast cancer risk in Italy.

BACKGROUND: The relation between the intake of sugar and sweets and the risk of breast cancer has been considered in ecological, prospective and case-control studies, but the results are unclear. We analyzed such a relation in a case-control study conducted between 1991 and 1994 in Italy. PATIENTS AND METHODS: Cases were 2569 women with histologically confirmed incident breast cancer and controls were 2588 women admitted to hospital for acute, non-neoplastic, non-hormone-related conditions. Information on diet was based on an interviewer-administered questionnaire tested for reproducibility and validity. The odds ratios (OR) and 95% confidence intervals (CI) were computed by multiple logistic regression equations. RESULTS: Compared with women with the lowest tertile of intake, women in the highest tertile of intake of desserts (including biscuits, brioches, cakes, puffs and ice-cream) and sugars (including sugar, honey, jam, marmalade and chocolate) had multivariate ORs of 1.19 (95% CI 1.02-1.39) and 1.19 (95% CI 1.02-1.38), respectively. The results were similar in strata of age, body mass index, total energy intake and other covariates. CONCLUSIONS: We found a direct association between breast cancer risk and consumption of sweet foods with high glycemic index and load, which increase insulin and insulin growth factors.

History of weight and obesity through life and risk of benign prostatic hyperplasia.

OBJECTIVE: The relation of anthropometric measures, diabetes, hypertension and hyperlipidemia with benign prostatic hyperplasia (BPH) risk was investigated. DESIGN: Hospital-based case-control study. SUBJECTS: Cases were 1369 men with histologically confirmed BPH, and controls were 1451 men below 75 y, admitted to hospital for acute non-neoplastic diseases. MEASUREMENTS: Using a structured questionnaire, trained interviewers collected information on self-reported height and weight, and measured waist and hip circumference of patients. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. RESULTS: Compared to the corresponding lowest quartile, the OR for the highest one were 0.76 (95% CI 0.59-0.98) for body weight, 0.71 (95% CI 0.54-0.94) for waist-to-hip ratio and 0.87 (95% CI 0.70-1.09) for body mass index (BMI, kg/m(2)). Compared to a lowest lifelong BMI <20.7 kg/m(2), the OR was 1.56 (95% CI 1.25-1.95) for a lowest lifelong BMI > or =23.7 kg/m(2). The OR was 0.74 (95% CI 0.60-0.93) for a lifelong increase of BMI > or =6.1 kg/m(2), compared to <1.6 kg/m(2). No association emerged for history of diabetes, hypertension and hyperlipidemia. CONCLUSIONS: Overweight was modestly, inversely related to BPH. The hypothesis of reduced testosterone levels in obese individuals may explain the different BPH risk and need to be tested.

Diabetes mellitus and the risk of prostate cancer in Italy.

OBJECTIVE: We investigated the relation between diabetes and the risk of prostate cancer, as epidemiological results are controversial. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study shows no material association between diabetes and prostate cancer risk.

Risk of melanoma and vitamin A, coffee and alcohol: a case-control study from Italy.

Limited information is available on the association between the risk of cutaneous malignant melanoma (CMM) and dietary factors. The issue was investigated using data from a case-control study conducted in Italy between 1992 and 1994, including 542 patients with incident, histologically confirmed CMM and 538 controls, admitted to the same hospitals as cases for non-dermatologic and non-neoplastic diseases. We found a significant inverse association between vitamin A intake and CMM risk. The multivariate odds ratio, after allowance for phenotypic characteristics and history of sunburns, for the highest, compared with the lowest, quartile of intake was 0.71 (95% confidence interval (CI) 0.50-1.02) for beta-carotene, 0.57 (95% CI 0.39-0.83) for retinol, and 0.51 (95% CI 0.35-0.74) for total vitamin A. We found no appreciable association of CMM risk with selected food items, including fish, meat, vegetables, fruit, dairy products, wholemeal bread, alcohol, coffee and tea drinking. Consumption of tea appeared to have a protective effect on CMM risk. The relations with measures of dietary vitamin A are, however, moderate compared with the associations between phenotypic characteristics, sun exposure and number of naevi and CMM risk.

Pizza and risk of acute myocardial infarction.

OBJECTIVES: Pizza eating has been favourably related to the risk of cardiovascular disease, but the data are limited. To evaluate the potential role of pizza consumption on the risk of acute myocardial infarction (AMI), we considered data from an Italian study. DESIGN: We conducted a hospital-based case-control study on 507 cases of nonfatal AMI and 478 controls in Milan, Italy, between 1995 and 1999. RESULTS: The multivariate odds ratios were 0.78 for occasional, 0.62 for regular and 0.44 for frequent eaters. The estimates were similar across strata of age, sex, smoking and other major covariates. CONCLUSIONS: Some of the ingredients of pizza have been shown to have a favourable influence on the risk of cardiovascular disease. However, there is no single explanation for the present findings. Pizza may in fact represent a general indicator of Italian diet, that has been shown to have potential cardiovascular benefits.