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.

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.

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.

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.

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.

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 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.

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.

n-3 Polyunsaturated fatty acids, fish, and nonfatal acute myocardial infarction.

BACKGROUND: The relation between n-3 polyunsaturated fatty acids (PUFAs), fish intake, and risk of coronary heart disease is controversial. METHODS AND RESULTS: An Italian case-control study including 507 patients with nonfatal acute myocardial infarction (AMI) and 478 hospital controls found a multivariate odds ratio (OR) of 0.67 (95% CI, 0.47 to 0.95) for the highest n-3 PUFA intake and 0.68 (95% CI, 0.47 to 0.98) for an intake of >1 portion of fish per week compared with >/=2 portions per week. CONCLUSIONS: Small amounts of n-3 PUFAs may be inversely related to AMI risk in this low-risk population.

Fruit and vegetable consumption and cancer risk in a Mediterranean population.

Ecological, case-control, and cohort studies present convincing evidence that diets rich in fresh fruit and vegetables protect against several common epithelial neoplasms. Studies of the Mediterranean diet are of particular interest to better understand and quantify this effect in view of the frequency and range of fruit and vegetable consumption by these populations. We review the results of a large-scale, Italian, case-control study of dietary intake of fruit and vegetables and risk of cancer at several sites. The relative risks (RRs) for most common neoplasms ranged from 0.2 to 0.5 for the highest compared with the lowest tertile of vegetable intake. Protective effects of vegetables were also observed against hormone-related neoplasms. Higher intakes of fruit were related to a reduced RR for cancers of the oral cavity and pharynx, esophagus, stomach, or larynx, as well as of the urinary tract, although protection was less evident for other digestive tract sites, as well as for other epithelial cancers. No association was observed between fruit and vegetable consumption and nonepithelial neoplasms. For upper respiratory and digestive tract cancers, population attributable risks for fresh vegetable and fruit intake ranged from 18% to 40% in men and from 15% to 30% in women; attributable risks for fresh vegetable and fruit intake, combined with tobacco and alcohol, exceeded 85% for men and 55% for women.

Refined-cereal intake and risk of selected cancers in italy.

BACKGROUND: Although consumption of whole-grain foods seems to reduce the risk of several types of neoplasms, the potential influence of a diet rich in starches and refined grains is less clear. OBJECTIVE: We studied the relation between the frequency of consumption of refined cereals (bread, pasta, or rice) and the risk of selected neoplasms. DESIGN: This was an integrated series of case-control studies conducted in northern Italy between 1983 and 1993. The subjects were patients admitted to the major teaching and general hospitals in Milan and Pordenone with incident, histologically confirmed cancers: 343 with cancer of the oral cavity and pharynx, 94 with cancer of the esophagus, 146 with cancer of the larynx, 745 with cancer of the stomach, 955 with cancer of the colon, 625 with cancer of the rectum, and 428 with cancer of the thyroid. The control subjects were 3526 patients admitted to the same network of hospitals for acute nonneoplastic conditions unrelated to long-term modification of diet. Odds ratios (ORs) for consecutive tertiles of refined-cereal consumption were computed after allowance for sociodemographic variables, education, smoking status, alcohol consumption, body mass index, and consumption of fruit, vegetables, and whole-grain foods. RESULTS: The ORs for the highest tertile of refined-cereal intake were 1.6 for cancer of the oral cavity, pharynx, esophagus, or larynx; 1.5 for stomach cancer; 1.5 for colon cancer; 1.3 for cancer of the rectum; and 2.0 for thyroid cancer. The trends in risk were significant for all neoplasms considered. CONCLUSION: Consumption of refined cereals was associated with an increased risk of cancers of the large bowel, the stomach, and other selected digestive and nondigestive sites.

Attributable risk for laryngeal cancer in northern Italy.

Using data from a case-control study conducted between 1986 and 1992 in Northern Italy on 367 cases of laryngeal cancers (350 men and 17 women) and 1931 hospital controls (1373 men and 558 women), we estimated the relative risks (RR) and the population attributable risks (AR) for laryngeal cancer in relation to tobacco and alcohol consumption and a diet containing little fresh fruit and vegetables (low beta-carotene intake). In men, the RR and their 95% confidence interval (CI), derived from multiple logistic regression, including terms for center, age, and education, plus, simultaneously, tobacco, alcohol, and beta-carotene) were 3.3 (95% CI, 1.9 to 5.5) for ex- or moderate smokers (< 15 cigarettes/day) and 8.8 (95% CI, 5.2 to 14.8) for heavy current smokers compared to never smokers; the RR were 1.5 (95% CI, 1.0 to 2.2) for drinkers of 6 to < 8 alcoholic drinks/day and 2.2 (95% CI, 1.6 to 3.0) for drinkers of 8 or more drinks/day compared to teetotallers or moderate drinkers; with respect to carotene intake the RR were 1.4 (95% CI, 1.0 to 2.0) for the intermediate tertile and 1.8 (95% CI, 1.3 to 2.5) for the lowest tertile, as compared to the highest tertile of intake. AR were estimated assuming a multiplicative model: the single factor with the largest AR was smoking, which accounted for about 77% of laryngeal cancers in men; alcohol intake explained about 25% of cases, low beta-carotene intake accounted for about 18% of cases, and together the three factors were responsible for about 86% of laryngeal cancers in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Attributable risk for oral cancer in northern Italy.

Using data from a case-control study conducted between 1984 and 1992 in the provinces of Milan and Pordenone, northern Italy, on 439 cases of oral and pharyngeal cancers and 2106 hospital controls, we computed the population attributable risk for oropharyngeal cancer in relation to tobacco, alcohol, and a measure of low beta-carotene intake. Two different models were used for estimating relative risks, one assuming that the three factors act multiplicatively on the relative risk and the second estimating separately each combination of alcohol and tobacco and assuming a multiplicative model only for beta-carotene. The estimated attributable risks were similar for the two models considered. For both models and both sexes, the single factor with the highest attributable risk was smoking, which accounted for 81-87% of oral cancers in males and for 42-47% in females. Alcohol explained about 60% of male cases, but only 15% of female ones, and low beta-carotene accounted for 24% of total cases (25% of males, 17% of females). Together the three factors were responsible for 91-94% of oropharyngeal cancers in males, 51-57% in females, and 85-88% in both sexes combined. The present knowledge of major identified risk factors could, in principle, reduce the burden of the disease in Italy from 2400 to about 200 deaths per year for males and from 500 to 230 for females, thus explaining the difference in incidence and mortality between the two sexes.

Hormone replacement treatment and breast cancer risk: an age-specific analysis.

The relationship between hormone replacement treatment (HRT) and breast cancer risk was considered in age-specific groups of women, combining data from two case-control studies conducted between 1983 and 1994 in six Italian centers. Cases were comprised of 5984 women, below age 75 years, with histologically confirmed breast cancer, and controls were comprised of 5504 women admitted to the hospital for a wide spectrum of acute, nonneoplastic, nonhormone-related diseases. Ever-use of HRT was reported by 6.1% of the cases and 5.5% of the controls, corresponding to a multivariate odds ratio (OR) of 1.2 [95% confidence interval (CI), 1.0-1.4]. A significant trend in risk with duration of use was observed. Separate analysis for women < 55, 55-64, and 65-74 years old at diagnosis showed that the excess risk of breast cancer associated with ever-use of HRT was not observed in the youngest age group (OR, 0.9) and increased with age at diagnosis to 1.2 (95% CI, 0.9-1.5) for women 55-64 years old and 1.6 (95% CI, 1.2-2.3) for those 65-74 years old at diagnosis. A significant trend in risk with duration was observed only in the oldest group (65-74 years old), with ORs of 1.6 (95% CI, 1.1-2.3) and 2.2 (95% CI, 1.1-4.7), respectively, for < 60 and > or = 60 months of use. Thus, this study suggests that the relationship between HRT and breast cancer risk is influenced by age at diagnosis and that any risk-benefit assessment is particularly critical for women using HRT several years after menopause.

Risk factors for esophageal cancer in lifelong nonsmokers.

Information on the etiology of esophageal cancer in lifelong nonsmokers is of interest to understand and quantify risk factors for the disease in the absence of the residual confounding by tobacco. Of a total of 316 cases with histologically confirmed incident cancers of the esophagus, 46 (17 males and 29 females) who described themselves as lifelong nonsmokers were selected to assess esophageal cancer risk in the absence of potential confounding and interactive effects of smoking. These patients were compared to 230 lifelong nonsmoker controls (85 males and 145 females) admitted to hospital for acute, nonneoplastic, non-alcohol-related conditions. The major risk factor for cancer of the esophagus in lifelong nonsmokers was elevated alcohol consumption: compared to drinkers of fewer than 4 drinks per day the relative risk (RR) was 2.7 (95% confidence interval, 1.1-6.8) for 4 to fewer than 8 drinks, and 5.4 (95% confidence interval, 1.4-21.0) for 8 or more drinks, with a significant trend in risk. Among selected indicator foods considered, significant protective effects were observed for fish (RR = 0.5 for the highest consumption tertile), green vegetables (RR = 0.6), and fresh fruit intake (RR = 0.3). Consequently, there was a significant inverse relationship with an estimate of beta-carotene intake (RR = 0.5 and 0.4, respectively, for the middle and highest tertiles of intake versus the lowest), with a significant trend in risk. The estimated RR for the highest alcohol consumption and lowest beta-carotene intake category was 8.6, and these two factors together explained over 45% of cases. Gastrectomy and family history of cancer of the esophagus were also associated with increased risk (RR = 4.6 and 4.3, respectively).

Risk factors for epithelial ovarian cancer in women under age 45.

Risk factors for ovarian cancer in young women were investigated using data from a case-control study conducted between 1983 and 1992 in Milan, northern Italy, on 194 women below age 45 with histologically confirmed incident cancers of the ovary and 710 controls admitted to the same network of hospitals for acute non-gynecological, nonhormonal and non-neoplastic diseases. An elevated relative risk (RR) of ovarian cancer was found among women reporting 12 or more years of education [RR 1.6, 95% confidence intervals (CI) 1.0-2.03] and belonging to the highest social class (RR 1.8, 95% CI 1.1-3.0). Women whose mothers had had ovarian cancer had a multivariate RR of 2.7 (95% CI 0.7-10.5) compared to those with no family history. Menarche above age 13 and irregular menstrual cycles were significantly protective against ovarian cancer (RR 0.6 for both risk factors). There was a significant inverse relationship with abortions, the RR being 0.6 both for spontaneous and for induced abortions, while protection of parity was not significant. Higher risks of ovarian cancer were observed in women having first or last birth when older than 30 years (RR 2.0 and 2.4, respectively, compared to those delivering under age 25). A significant trend toward an increased risk of ovarian cancer was also observed with decreasing time since last birth. Compared with women whose last birth occurred 10 or more years before diagnosis, the RR was 2.1 (95% CI 1.1-3.9) for those reporting a birth during the last 5 years. The RR for oral contraceptive users was 0.7 (95% CI 0.5-1.0) and the protection increased with duration, with RR of 0.3 (95% CI 0.1-0.7) for 5 or more years of use. This study indicates that, although the incidence of ovarian cancer is higher in older women, recognised risk and protective factors are similar below age 45. An excess risk in the few years after a term delivery is also suggested.