Childhood infectious diseases and risk of non-Hodgkin's lymphoma according to the WHO classification: A reanalysis of the Italian multicenter case-control study.

Since 1960, incidence of non-Hodgkin's lymphoma (NHL) has been increasing in most industrialized countries, but causes of this trend remain unclear. A role of the decreased exposure to infectious agents during childhood has been proposed. Our study evaluates the association between common childhood infectious diseases and the risk of NHL and its major subtypes by a reanalysis of the Italian multicenter case-control study. After exclusion of next-of-kin interviews, 1,193 cases, diagnosed between 1990 and 1993, and 1,708 population-based controls were included in the analyses. OR estimates were obtained by logistic regression, adjusting for gender, age, residence area, education, smoking habit and exposure to radiations, pesticides and aromatic hydrocarbons. Among B-cell lymphomas (n = 1,102) an inverse association was observed for rubella (OR = 0.80, 95% CI: 0.65-0.99), pertussis (OR = 0.74, 95% CI: 0.62-0.88) and any infection (OR = 0.75, 95% CI: 0.61-0.93). A negative trend by number of infections was observed, which was more evident among mature B-cell lymphoma (OR = 0.66 for three infections or more, 95% CI: 0.48-0.90). Our results indicate a potential protective role of common childhood infections in the etiology of B-cell NHL.

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

BACKGROUND: Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. METHODS: We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). RESULTS: Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. CONCLUSIONS: Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.

Childhood infectious diseases and risk of leukaemia in an adult population.

Our study is aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population. A reanalysis of a large population-based case-control study was carried out. Original data included 1,771 controls and 649 leukaemia cases from 11 Italian areas. To contain recall bias, the analysis was restricted to subjects directly interviewed and with a good quality interview (1,165 controls and 312 cases). Odds ratios (ORs) and their related 95% confidence intervals (95% CIs) were estimated by unconditional polychotomous logistic regression model adjusting for age, gender and occupational and lifestyle exposures. A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45-0.97), measles (OR = 0.57, 95% CI: 0.39-0.82) and pertussis (OR = 0.66, 95% CI: 0.45-0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32-0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general "hygiene hypothesis" could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated.

[Skin cancer risk factors in childhood: findings of a survey conducted within Italian areas with a different incidence of melanoma]. / Infanzia e fattori di rischio per tumori della cute: risultati di un indagine in aree italiane a diversa incidenza di melanoma cutaneo.

OBJECTIVE: to evaluate the association between phenotype and sun sensitivity factors, sun protection behavior, ethnicity and the area of residence in school-aged children. DESIGN: a cross-sectional study in the framework of a survey of children using a self-administered questionnaire to be filled in by parents. SETTING AND PARTICIPANTS: 56390 children attending primary schools located in the Italian provinces of Brindisi, Rome, Forlì and Genova, in the period between 1998-2002. MAIN OUTCOME MEASURES: Odds Ratios (ORs) and their relative 95% Confidence Intervals (95% CI) are to be computed through univariate and multivariate logistic regression models. RESULTS: "FOTO positive" phenotype, a proxy variable of the fair phenotype, was directly and significantly associated with the tendency to sunburn (OR 4.75; 95% CI 4.54-4.96), the use of sunscreens (OR 1.79; 95% CI 1.63-1.97), the number of grandparents born in the northern areas (OR 1.63; 95% CI 1.45-1.83, for four northern grandparents versus none), the presence of freckles on the face (OR 1.62; 95% CI 1.53-1.72) and of naevi on the left forearm (OR 1.20; 95% CI 1.15-1.26). A positive association was also found for the residence in the northern areas using the area of Brindisi as the reference category, (Rome: OR 1.02; 95% CI 0.95-1.10; Forlì: OR 1.05; 95% CI 0.96-1.15; Genova: OR 1.16; 95% CI 1.08-1.26); the ORs increase with latitude, as does the incidence rate of melanoma in Italy. An inverse association was observed with the male sex (OR 0.92; 95% CI 0.88-0.96), the increase of school-class level (OR 0.65; 95% CI 0.60-0.69, for the highest versus the lowest school-class level) and the ability to tan (OR 0.40; 95% CI 0.36-0.43). CONCLUSION: these findings confirmed that the fairness phenotype is associated with other skin cancer risk factors in children and pointed out that the high-risk phenotype has a geographical distribution consistent with the pattern of melanoma incidence in the Italian areas covered by the study.

Skin cancer risk factors among primary school children: investigations in Western Hungary.

OBJECTIVE: To evaluate the factors associated with sunburns and with sun protection practice in Hungarian primary school children. METHOD: We investigated children's (the median age: 8, range 5 to 12 years) and parents' assessment of sun sensitivity and sun protection characteristics in cities Gyor and Zalaegerszeg (Hungary) in 2004. This cross-sectional study was part of a programme intended to increase children's and parents' awareness of harmful effects of excessive sunbathing. Analyses were based on 1804 multiple choice questionnaires. RESULTS: At multivariate analysis a significant association between sunburns and fairness of complexion, freckles, use of sunscreens and T-shirts, and higher school-class level was observed. Sunburn was inversely associated with hat-wearing. Parents were more likely to apply sunscreen to children with light eyes and to the younger ones, to protect fair skinned children with T-shirts; to protect males and children with fair skin and light eyes with hats. CONCLUSION: Since environmental factors play an important role in the development of skin cancer, morbidity could be reduced by primary prevention. Sun protection habits should therefore be taught early in life, and parents' behaviour adapted. Phenotype is not only related to sunburns but it also appears to influence parents' sun safety behaviour.

Aspirin and risk of renal cell cancer in Italy.

Aspirin and nonsteroidal anti-inflammatory drugs have been related to decreased risk of several cancers, but studies on the relation with the risk of renal cell cancer (RCC) are inconsistent. A case-control study of RCC was conducted in Italy between 1992 and 2004. Cases were 755 patients with incident, histologically confirmed RCC, and controls were 1297 patients in hospital for acute non-neoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were conditioned on center, sex, age, and year of interview, and adjusted for education, smoking, alcohol consumption, diabetes, and hypertension. Regular use of aspirin for at least 6 months was reported by 67 cases and 99 controls, corresponding to an OR of 0.98 (95% CI 0.69-1.38). The ORs were 0.91 (95% CI 0.55-1.50) in regular users for less than 3 years, and 1.04 (95% CI 0.67-1.63) in users for 3 years or longer; 0.47 (95% CI 0.20-1.12) when aspirin was used as analgesic and 1.10 (95% CI 0.75-1.62) when it was used for cardiovascular disease prevention. No significant heterogeneity was found for regular use of aspirin across strata of age and sex. This study, based on a large dataset, suggests that regular use of aspirin did not increase RCC risk.

[Skin cancer risk factors in childhood: findings of a survey in an Italian area characterized by atypical migration]. / Infanzia e fattori di rischio per tumori della cute: risultati di un'indagine in un'area italiana oggetto di una migrazione atipica.

OBJECTIVE: to evaluate the association of different phenotypes with sun sensitivity factors, sun protection behavior and ethnicity in school-age children. DESIGN: cross sectional study in the framework of a survey of children using a self-administered questionnaire. SETTING AND PARTICIPANTS: 35412 children attending primary schools in the provinces of Latina and Rome, located in the Lazio region (Italy), in the 1998-2001 time period. MAIN OUTCOME MEASURES: Odds Ratios (ORs) and their relative 95% Confidence Intervals (95% CI) computed through univariate and multivariate logistic regression models. RESULTS: "FOTO positive" phenotype, a proxy variable of the fair phenotype, was directly and significantly associated with the tendency to sunburn (OR 4.64; 95% CI 4.39-4.89), the presence of freckles on the face (OR 1.65; 95% CI 1.55-1.77), of naevi on the left forearm (OR 1.18; 95% CI 1.12-1.25), the number of grandparents born in northern areas (OR 1.54; 95% CI 1.15-2.07, for four northern grandparents versus none), the residence in Latina Province (OR 1.13; 95% CI 1.07-1.20) and the use of sunscreens (OR 1.70; 95% CI 1.55-1.88). An inverse association was observed with the male sex (OR 0.91; 95% CI 0.86-0.96), the increase of school-class level (OR 0.66; 95% CI 0.61-0.72, for the highest versus the lowest school-class level) and the ability to tan (OR 0.38; 95% CI 0.34-0.42). CONCLUSION: These findings confirmed that fairness of phenotype is associated in children with other skin cancer risk factors as well as ethnicity and parents' sun protection behavior.

Coffee, decaffeinated coffee, tea intake, and risk of renal cell cancer.

The relation between coffee, decaffeinated coffee, and tea intake and renal cell carcinoma (RCC) risk was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident histologically confirmed RCC and controls were 1,534 patients in hospital for acute non neoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex, and age. Coffee intake (mostly espresso and mocha) was not associated with RCC risk, with an OR of 1.02 (95% CI 0.73-1.43) in drinkers of > or = 4 cups/day compared with drinkers of < 1 cup/day. The corresponding ORs were 1.34 (95% CI 0.87-2.07) in men and 0.67 (95% CI 0.38-1.18) in women, 1.91 (95% CI 0.85-4.31) in current smokers and 0.74 (95% CI 0.41-1.31) in never smokers, with no trend in risk with dose. No relation was observed with decaffeinated coffee (OR = 1.38, 95% CI 0.94-2.03 for drinkers compared with nondrinkers) and tea intake (OR = 0.78, 95% CI 0.59-1.05 for drinkers of > or = 1 cup/day compared with nondrinkers). No significant heterogeneity was found for coffee intake across strata of age, education, body mass index, and consumption of sugar. This study, based on a large dataset, provides further evidence that coffee, decaffeinated coffee, and tea consumption are not related to RCC risk.

Reproductive, menstrual, and other hormone-related factors and risk of renal cell cancer.

A role of hormone-related factors in renal cell cancer (RCC) etiology has been hypothesized, but the epidemiological evidence is inconsistent. The present study aimed at evaluating the effect of reproductive, menstrual and other gender-specific variables on RCC risk among women. This study is part of a larger hospital-based, case-control study on RCC risk, conducted in northern, central and southern Italy. Cases were 273 women, below age 80, with histologically confirmed, incident RCC. Controls were 546 women hospitalized for acute, nonneoplastic conditions, frequency-matched to cases by age and center. Odds ratios (OR) and 95% confidence intervals (CI) were computed using multiple logistic regression models. RCC risk was inversely related to age at first birth (OR = 0.7, 95% CI 0.5-1.0, for >/= 25 years vs. <25 years). Hysterectomy was found to double RCC risk (OR = 2.3, 95% CI 1.3-4.2). A negative association of borderline-statistical significance emerged for age at menarche, whereas, no associations were found between RCC risk and parity, menopausal status, age at menopause and use of hormone replacement therapy or oral contraceptives. Our findings give support to a role of hysterectomy in increasing RCC risk without corroborating, however, a major role of female hormone-related factors.

Risk of leukemia and multiple myeloma associated with exposure to benzene and other organic solvents: evidence from the Italian Multicenter Case-control study.

BACKGROUND: While there is a general consensus about the ability of benzene to induce acute myeloid leukemia (AML), its effects on chronic lymphoid leukemia and multiple myeloma (MM) are still under debate. We conducted a population-based case-control study to evaluate the association between exposure to organic solvents and risk of myeloid and lymphoid leukemia and MM. METHODS: Five hundred eighty-six cases of leukemia (and 1,278 population controls), 263 cases of MM (and 1,100 population controls) were collected. Experts assessed exposure at individual level to a range of chemicals. RESULTS: We found no association between exposure to any solvent and AML. There were elevated point estimates for the associations between medium/high benzene exposure and chronic lymphatic leukemia (OR = 1.8, 95% CI = 0.9-3.9) and MM (OR = 1.9, 95% CI = 0.9-3.9). Risks of chronic lymphatic leukemia were somewhat elevated, albeit with wide confidence intervals, from medium/high exposure to xylene and toluene as well. CONCLUSIONS: We did not confirm the known association between benzene and AML, though this is likely explained by the strict regulation of benzene in Italy nearly three decades prior to study initiation. Our results support the association between benzene, xylene, and toluene and chronic lymphatic leukemia and between benzene and MM with longer latencies than have been observed for AML in other studies.

Family history and the risk of oral and pharyngeal cancer.

Scanty data are available on familial risk in oral and pharyngeal cancer. The relationship between oral and pharyngeal cancer and family history of cancer in first-degree relatives was investigated using data from a multicentric case-control study conducted in Italy and Switzerland between 1992 and 2005 on 956 cases aged less than 79 years, with histologically confirmed incident oral and pharyngeal cancer, and 2362 controls admitted to hospital for acute, nonneoplastic conditions. Logistic regression models conditioned on sex, age, study centre, and including terms for education, tobacco smoking, alcohol drinking, and number of siblings were used to estimate the odds ratios (OR) of oral and pharyngeal cancer. The multivariate ORs were similar for a family history of oral and pharyngeal cancer (2.6, 95% confidence interval, CI, 1.5-4.5) and laryngeal cancer (3.8, 95% CI, 2.0-7.2). The OR was 3.1 (95% CI, 2.0-4.8) for oral and pharyngeal cancer and laryngeal cancer combined. The OR was 7.1 (95% CI, 1.3-37.2) for subjects with 2 or more first-degree relatives with oral and pharyngeal/laryngeal cancers. Significant increases in risk were also observed for a family history of melanoma (OR = 5.8; 95% CI, 1.3-26.4) and lung cancer (OR = 1.4; 95% CI, 1.0-2.0). Compared to subjects without family history, nonsmokers, and non or moderate drinkers, the OR was 42.6 for current smokers, heavy drinkers with family history. History of oral and pharyngeal cancer and laryngeal cancer is a strong determinant of oral and pharyngeal cancer risk, independent from tobacco and alcohol.

Risk factors for prostate cancer in men aged less than 60 years: a case-control study from Italy.

OBJECTIVES: To analyze the relationship between selected risk factors and prostate cancer risk in men younger than 60 years, using data from a large, multicenter, case-control study conducted in Italy. METHODS: Cases were 219 patients, aged 45 to 59 years, with histologically confirmed prostate cancer, and controls were 431 men of the same age group, admitted in hospital for acute, non-neoplastic diseases. RESULTS: A family history of prostate cancer (odds ratio [OR] = 5.5), brain cancer (OR = 3.7), and leukemia (OR = 6.2) were associated with prostate cancer risk. A significantly increased risk was found for high education level (OR = 3.3 for 12 or more years versus less than 7 years) and a decreased risk for physical activity (OR = 0.5 for active versus inactive). Coffee consumption was directly associated with risk of prostate cancer (OR = 1.9 for the third versus the first tertile). Bread consumption was directly related (OR = 1.6) and consumption of raw and total vegetables inversely related (OR = 0.6) to prostate cancer risk, although these associations were of borderline significance. No association emerged with marital status, body mass index, history of diabetes, alcohol drinking, and other considered foods. CONCLUSIONS: This study confirms that some recognized risk factors, including family history of prostate cancer, high level of education, and low physical activity, are associated with prostate cancer risk in middle-aged men.

Onion and garlic intake and the odds of benign prostatic hyperplasia.

OBJECTIVE: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy. METHODS: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake. RESULTS: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata. CONCLUSIONS: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.

Flavonoids and the risk of oral and pharyngeal cancer: a case-control study from Italy.

The intake of flavonoids has been inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. We used data from a case-control study conducted in Italy between 1992 and 2005 to examine the relationship between flavonoid intake and oral and pharyngeal cancer risk. The study included 805 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,081 hospital controls admitted for acute, nonneoplastic conditions. We have applied data on food and beverage content of six major classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. The odds ratios (OR) were calculated using multiple logistic regression models, conditioned on study center, sex, and age. After adjustment for education, tobacco, alcohol, body mass index, and non-alcohol energy intake, ORs for the highest versus the lowest quintile of intake were 0.51 [95% confidence intervals (95% CI), 0.37-0.71] for flavanones, 0.62 (CI, 0.43-0.89) for flavonols, and 0.56 (95% CI, 0.40-0.78) for total flavonoids. No significant association emerged for isoflavones (OR, 0.90), anthocyanidins (OR, 0.86), flavan-3-ols (OR, 0.84), and flavones (OR, 0.75). The ORs were consistent across strata of age, sex, education, body mass index, tobacco, and alcohol. After allowance for vegetable and fruit consumption, the inverse relations with total flavonoids and flavanones remained significant, whereas that with flavonols became nonsignificant. None of the associations were significant after further allowance for vitamin C, probably on account of the high collinearity between these compounds.

Fibre intake and renal cell carcinoma: a case-control study from Italy.

Only 2 previous studies, conducted in Australia, United States and northern Europe, considered the role of dietary fibre intake on renal cell carcinoma (RCC) risk, and both showed a modest, inverse association. Therefore, we investigated in depth the topic of fibres and RCC, using data from a multicenter case-control study conducted in Italy from 1992 to 2004, including 767 cases with incident, histologically confirmed RCC and 1,534 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. The continuous OR for an increase in intake equal to the difference between the 80th and the 20th percentile were 0.94 (95% CI: 0.82-1.08) for total dietary fibre, 0.98 (95% CI: 0.85-1.13) for soluble noncellulose polysaccharides, 0.92 (95% CI: 0.80-1.05) for total insoluble fibre, 0.90 (95% CI: 0.78-1.04) for cellulose, 0.95 (95% CI: 0.84-1.06) for insoluble noncellulose polysaccharides and 1.06 (95% CI: 0.93-1.21) for lignin. With reference to the sources of fibre, we found an inverse association with vegetable fibre (OR = 0.84, 95% CI: 0.73-0.97), but no association with fruit (OR = 0.98, 95% CI: 0.86-1.12) and grain fibre (OR = 1.05, 95% CI: 0.95-1.15). The inverse association with vegetable fibre may reflect a real favorable effect, or be an indicator of a beneficial role of a diet rich in vegetable on RCC risk.

Renal cell cancer and body size at different ages: an Italian multicenter case-control study.

An increased risk of renal cell cancer (RCC) has been reported in overweight persons. The authors aimed to clarify which anthropometric measures are associated with risk of RCC and whether risk may vary according to selected variables. Between 1992 and 2004, they carried out an Italian multicenter case-control study including 767 (494 men, 273 women) incident cases of RCC and 1,534 hospital controls, frequency-matched to cases. To estimate odds ratios and 95% confidence intervals, they used conditional logistic regression matched on study center, sex, and age and adjusted for period of interview, years of education, smoking habits, and family history of kidney cancer. Using body-size measurements taken 1 year prior to diagnosis/interview, the authors found an odds ratio of 1.3 (95% confidence interval (CI): 1.0, 1.7) among obese persons (body mass index (BMI; weight (kg)/height (m)(2)) > or =30) versus normal-weight persons (BMI <25) and an odds ratio of 1.5 (95% CI: 1.1, 2.0) among persons in the highest tertile of waist-to-hip ratio. Direct associations emerged for BMI > or =30 (vs. <25) at ages 30 years (odds ratio = 1.5, 95% CI: 1.0, 2.3) and 50 years (odds ratio = 1.5, 95% CI: 1.1, 2.0). The direct association with waist-to-hip ratio was stronger among women than among men. RCC risks among overweight and obese persons were apparently higher in never smokers, persons with the clear-cell histologic type, and persons with a Fuhrman nuclear grade of G3-G4.

Risk factors for ovarian cancer histotypes.

To analyse the risk factors for different histologic types of ovarian cancer, we conducted a case-control study. The cases included 750 women with incident, histologically confirmed invasive epithelial ovarian cancer subdivided into: 493 serous, 81 mucinous, 78 endometrioid, and 98 other histologies. The controls included 2411 women admitted to the same hospitals as cases. The odds ratios for women with three or more births, in comparison with nulliparae, were 0.6 for serous, 0.4 for endometrioid, 1.0 for mucinous and 0.7 for other histological types of ovarian cancer. Family history of ovarian/breast cancer was associated to the risk of all ovarian cancer types, except mucinous ones. Selected dietary factors were less strongly directly (meat and starch), or inversely (fish and vitamin E) related to mucinous than to other histological types of ovarian cancer. High occupational physical activity was inversely related to the risk of ovarian cancer, with no heterogeneity across histologies. In conclusion, the association of reproductive factors and of selected dietary habits was weaker for mucinous ovarian cancer than for other histologic types.

Dietary zinc and prostate cancer risk: a case-control study from Italy.

OBJECTIVES: Zinc concentration is higher in the prostate than in most other tissues. Since information on the role of zinc on prostate carcinogenesis is controversial, we analysed the issue in a case-control study. METHODS: Between 1991 and 2002, we conducted a multicentre hospital-based case-control study on prostate cancer in Italy. Cases included 1294 men with incident, histologically confirmed prostate cancer. Controls included 1451 patients admitted to the same hospitals as cases for a wide spectrum of acute non-neoplastic, non-hormone-related diseases. Zinc intake was computed from a valid and reproducible food frequency questionnaire, with the use of an Italian food composition database. Odds ratios (OR) of dietary intake of zinc and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models, after allowance for several covariates, including total energy. RESULTS: Compared with the lowest quintile, the OR for the highest quintile was 1.56 (95% CI, 1.07-2.26), with a significant trend in risk (p=0.04). The trend in risk was significant for advanced cancers only, the OR being 2.02 (95% CI, 1.14-3.59) for prostate cancers with a high Gleason score. CONCLUSIONS: In this large study we found a direct association between high zinc intake and prostate cancer risk, particularly for advanced cancers. Our findings allow one to exclude a favourable effect of zinc on prostate carcinogenesis.

Lifetime physical activity and the risk of renal cell cancer.

The relation between lifelong physical activity at work and during leisure-time and the risk of renal cell cancer (RCC) was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident, histologically confirmed RCC, and controls were 1,534 patients hospitalized for acute nonneoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex and age, and adjusted for main covariates. Compared to the lowest level of occupational physical activity, the multivariate OR of RCC for the highest level were 0.65 (95% CI 0.49-0.87) at age 12 years, 0.67 (95% CI 0.53-0.84) at age 15-19, 0.74 (95% CI 0.59-0.93) at age 30-39 and 0.71 (95% CI 0.55-0.92) at age 50-59 years, with significant inverse trends in risk. The inverse association was consistent in strata of sex, age at diagnosis, body mass index, smoking habit and alcohol drinking. No significant association was found for leisure-time physical activity. The inverse association between occupational physical activity and RCC risk, if real, may be related to the effects of insulin-like growth factors, or lipid peroxidation and about 9% of cases of RCC in Italy could be avoided by increasing physical activity. However the inverse association might involve confounding by indirect mechanisms, such as body composition or other social class correlates.

Flavonoids and the risk of renal cell carcinoma.

Intake of flavonoids has been inversely related to the risk of various common neoplasms, but limited data exist on renal cell carcinoma (RCC). We used data from a case-control study conducted between 1994 and 2002 in four Italian areas to study the relation between major flavonoid classes and RCC. The study included 767 cases with incident, histologically confirmed RCC and 1,534 hospital controls admitted for acute, nonneoplastic conditions and matched with cases by study center, sex, and quinquennia of age. We applied published data on food and beverage content of six major classes of flavonoids to dietary information collected through a validated food frequency questionnaire. After adjustment for major recognized confounding factors and total energy intake, the odds ratios for subjects in the highest versus the lowest quintile of intake were 0.80 [95% confidence interval (95% CI), 0.58-1.11] for total flavonoids, 0.76 (95% CI, 0.56-1.03) for isoflavones, 0.94 (95% CI, 0.60-1.47) for anthocyanidins, 0.77 (95% CI, 0.56-1.06) for flavan-3-ols, 0.90 (95% CI, 0.67-1.21) for flavanones, 0.68 (95% CI, 0.50-0.93) for flavones, and 0.69 (95% CI, 0.50-0.95) for flavonols. Allowance for vegetable and fruit consumption only partly explained these inverse relations. Thus, flavonoids, and particularly flavones and flavonols, may account, at least in part, for the favorable role of plant foods on RCC.