Micronutrients and the risk of renal cell cancer: a case-control study from Italy

The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41-0.75), and vitamin C (OR = 0.72, 95% CI = 0.54-0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59-1.08) for retinol, 0.82 (95% CI = 0.61-1.10) for alpha-carotene, 0.90 (95% CI = 0.68-1.20) for beta-carotene, 0.94 (95% CI = 0.73-1.21) for beta-criptoxanthin, 0.85 (95% CI = 0.63-1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57-1.01) for vitamin D, 0.75 (95% CI = 0.55-1.01) for thiamine, 0.88 (95% CI = 0.66-1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64-1.13), 0.85 (95% CI = 0.64-1.12) for folate and 0.80 (95% CI = 0.60-1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC.     

Nutrition and renal cell cancer

Epidemiologic evidence on the relation between nutrition and renal cell cancer is reviewed. Kidney cancer, comprising 1.7 percent of all malignant diseases diagnosed worldwide, shows about a 20-fold international variation in the incidence in men and 10-fold in women. This substantial variation indicates an important causal role of environmental factors. Renal cell (parenchymal) cancer (RCC) accounts for about 80 percent of all kidney cancers. While the etiology of RCC is incompletely understood, analytic epidemiologic studies provide consistent support for a positive association of obesity with risk of RCC; the dose-response observed supports a causal relationship. Only a few prospective studies, all of them limited in size, have been published, while ecologic and case-control studies suggest that diet may be important in the etiology of RCC. However, contradictory results and methodologic limitations in some casecontrol studies prevent definite conclusions concerning diet and RCC. A positive association of protein and fat intake, as well as their main food sources (meat, milk, fats), with risk of RCC-as suggested by ecologic studies—has no clear support in analytic epidemiologic studies. A protective effect of vegetables and fruits has been observed in most casecontrol studies, while the majority do not show an association between alcohol, coffee, and risk of RCC. Recent reports indicated an increased risk of RCC associated with consumption of fried/sautéed meat and low intakes of magnesium or vitamin E. An apparent positive association with total energy intake, perhaps due to bias, needs further investigation.This project was funded partially by the Swedish Cancer Society.     

Occupational exposures as risk factors for gastric cancer in Italy

Occupational associations with gastric cancer were investigated in a multicenter case-control study in Italy involving interviews with 640 histologically confirmed male cases and 959 controls, randomly selected from the resident populations of the study areas. From information on the three jobs each person held the longest, risks were evaluated according to employment in 35 occupations (ever or 21+ years) and to estimated exposure (ever or 21+ years) to six chemicals using a job-exposure matrix. All risk estimates were adjusted by personal, demographic, and dietary variables identified as gastric-cancer risk factors in previous analyses. The only significantly increased risk was observed for sailors, seamen, and allied groups (ever employed: odds ratio [OR]=2.9; 95 percent confidence interval [CI]=1.1–8.0; 21+ years: OR=3.1, CI=0.8–13). Nonsignificant increases after 21+ years of employment were observed for forestry workers, miners, and janitors and cleaners. Crude ORs were elevated significantly among farmers, but adjusting for demographic and lifestyle factors largely eliminated the association: a nonsignificant 30 percent excess risk remained for farm laborers, but there was no rise in risk among long-term farm laborers and no excess among farm owners. Application of the job-exposure matrix revealed excess risks of borderline significance associated with potential exposure to mineral dusts and nitrogen oxides. For subjects with 21+ years of potential exposure, nonsignificantly increased risks were related to mineral dusts, asbestos, fertilizers, and nitrosamines. Although possibly incomplete occupational histories and use of broad occupational codes likely resulted in some exposure misclassification, the results of this study indicate that occupation in general is not a strong risk factor for gastric cancer. The findings, however, are consistent with previous reports suggesting that certain occupational exposures may influence gastric cancer risk.This work was made possible by the financial support of the International Union against Cancer, Geneva, Switzerland, and the National Research Council, Rome, Italy.     

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.     

Low adiponectin levels are associated with renal cell carcinoma: a case-control study

Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case- control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32-month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR=0.76, p=0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra-abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans.     

Alcohol consumption and risk of renal cell cancer: the NIH-AARP diet and health study

Background:

The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear.

Method:

The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases).

Results:

Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and ⩾30 g per day was, 0.75 (0.63–0.90) and 0.71 (0.59–0.85), respectively, in men and 0.67 (0.42–1.07) and 0.43 (0.22–0.84), respectively, in women.

Conclusion:

Alcohol consumption was inversely associated with RCC in a dose–response manner. The inverse association may be extended to ⩾30 g per day of alcohol intake.     

Food groups and renal cell carcinoma: a case-control study from Italy

Although nutrition and diet have been related to renal cell carcinoma (RCC), the role of specific foods or nutrients on this cancer is still controversial. We evaluated the relation between a wide range of foods and the risk of RCC in an Italian case-control study including 767 patients (494 men and 273 women) younger than 79 years with incident, histologically confirmed RCC, and 1,534 controls (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, not related to long term diet modifications. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcohol drinking, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major confounding factors. A significant direct trend in risk was found for bread (OR = 1.94 for the highest versus the lowest intake quintile), and a modest excess of risk was observed for pasta and rice (OR = 1.29), and milk and yoghurt (OR = 1.27). Poultry (OR = 0.74), processed meat (OR = 0.64) and vegetables (OR = 0.65) were inversely associated with RCC risk. No relation was found for coffee and tea, soups, eggs, red meat, fish, cheese, pulses, potatoes, fruits, desserts and sugars. The results of this study provide further indications on dietary correlates of RCC, and in particular indicate that a diet rich in refined cereals and poor in vegetables may have an unfavorable role on RCC.     

Alcohol intake and renal cell cancer risk: a meta-analysis

Background:

An inverse association between alcoholic beverage intake and risk of renal cell cancer has been suggested in recent studies.

Methods:

We examined the association between alcoholic beverages and renal cell cancer risk in a meta-analysis. We identified relevant studies by searching the database of PubMed, EMBASE, and MEDLINE published through August 2011. We combined the study-specific relative risks (RRs) using a random-effects model.

Results:

A total of 20 case–control studies, 3 cohort studies, and 1 pooled analysis of cohort studies were included in the meta-analysis. We observed that alcoholic beverage intake was associated with a lower risk of renal cell cancer in combined analysis of case–control and cohort studies; for total alcoholic beverage intake, combined RRs (95% confidence intervals) comparing top with bottom categories were 0.76 (0.68–0.85) in case–control studies, and 0.71 (0.63–0.78) in cohort studies (P for difference by study design=0.02). The inverse associations were observed for both men and women and for each specific type alcoholic beverage (beer, wine, and liquor). Also, we found that one drink per day of alcoholic beverage conferred the reduction in renal cell cancer risk, but further drinking above that level did not add benefit.

Conclusion:

The findings from our meta-analysis support the hypothesis that alcoholic beverage intake is inversely associated with a lower risk of renal cell cancer, with moderate consumption conferring the protection and higher consumption conferring no additional benefits.     

Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy

Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case-control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8-20.3) than among women (OR = 4.2, CI 3.5-5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0-19, 20-39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6-4.2], 4.1 [CI 3.1-5.6]) and women (OR = 1.0, 2.7 [CI 1.7-4.1], 3.3 [CI 1.9-5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men.     

Alcoholic beverages and risk of renal cell cancer

Using a mailed questionnaire, we investigated the risk of renal cell cancer in relation to different types of alcoholic beverages, and to total ethanol in a large population-based case-control study among Swedish adults, including 855 cases and 1204 controls. Compared to non-drinkers, a total ethanol intake of >620 g month(-1) was significantly related to a decreased risk of renal cell cancer (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4-0.9; P-value for trend=0.03). The risk decreased 30-40% with drinking more than two glasses per week of red wine (OR 0.6, 95% CI 0.4-0.9), white wine (OR 0.7, 95% CI 0.4-1.0), or strong beer (OR 0.6, 95% CI 0.4-1.0); there was a clear linear trend of decreasing risk with increasing consumption of these beverages (P-values for trends <0.05).     

Risk of renal cell carcinoma in relation to blood telomere length in a population-based case-control study

Background:

There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case–control studies suggested an association between short blood telomere length (TL) and increased RCC risk.

Methods:

We conducted a large population-based case–control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models.

Results:

Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001).

Conclusion:

These data do not support the hypothesis that blood TL is associated with RCC. This population-based case–control study is, to our knowledge, the largest investigation to date of TL and RCC.     

Alcohol and colorectal cancer: a case-control study from northern Italy

The role of alcohol consumption in the etiology of colorectal cancer has been investigated in a case-control study conducted from 1985 to 1990 in the northern part of Italy, on 889 cases of colon cancer, 581 cases of rectal cancer, and 2,475 controls admitted to hospital for acute, non-neoplastic, nodigestive disordes. After allowance for age, education, study center, body mass index, and approximate total energy intake, no significant associations between alcohol intake and the risk of cancer of the colon or rectum were found (odds ratios [OR] for 42 drinks/week cf none =1.0 (95 percent confidence interval [CI]=0.8–1.4) and 0.7 (CI=0.5–1.0) for cancer of the colon and rectum, respectively). A significant increase in the risk of colon cancer with increasing alcohol consumption was, however, observed in females (OR for 28 drinks/week cf none = 1.8 (CI=1.1–3.0)). While the results of the present case-control study do not suggest that alcohol plays a role in the etiology of colon or rectum cancer overall, they provide a hint for a weak association between alcohol consumption and colon cancer among females which, because of the similarities with breast cancer, should be evaluated in the context of the possible relationship between colon cancer, alcohol intake, and female hormones.Drs Barra, Franceschi, and Guarneri, are with the Epidemiology Unit, Aviano Cancer Center Aviano, Italy. Dr Franceschi is also with the European Cancer Prevention Organisation (ECP), Epidemiology and Cancer Working Group, Brussels, Belgium. Drs Negri and La Vecchia are with the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also with the Institute of Social and Preventive Medecine, University of Lausanne, Lausanne, Switzerland. Address correspondence to Dr Barra, Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ., 33081 Aviano (PN) Italy. Support for this project was contributed by the Italian Association for Research on Cancer and the Italian League against Tumors, Milan and the Italian National Research Council (CNR Applied Project Clinical Applications of Oncological Research).     

Risk factors for renal cell carcinoma: results of a population-based case-control study

For a case-control study of risk factors for renal cell carcinoma, a mailed questionnaire was used to collect data on 518 cases and 1,381 population-based controls in Ontario, Canada. Active cigarette smoking increased risk twofold among males (odds ratio estimate [OR]=2.0, 95 percent confidence interval (CI)=1.4–2.8) and females (OR=1.9, CI=1.3–2.6). Passive smoking appeared to increase risk somewhat among nonsmokers (males: OR=1.6, CI=0.5–4.7; females: OR=1.7, CI=0.8–3.4). A high Quetelet index (QI) was associated with a twofold increase in risk in both sexes, although this was based on reported weight at age 25 years for males (OR=1.9, CI=1.2–3.1) and five years prior to data collection for females (OR=2.5, CI=1.4–4.6). Diuretic use was associated with significantly increased risk among females, but not among males. Phenacetin use increased risk, while acetaminophen use was not associated with altered risk, although few subjects used either compound. Multiple urinary tract infections increased risk, but only significantly in females (OR=1.9, CI=1.2–2.9). Our data indicate the need for further exploration of passive smoking and diuretics as risk factors, as well as elucidation of mechanisms by which high lifetime QI and frequent urinary-tract infections might increase risk of this cancer.Des Kreiger, Marrett, and Darlington are with the Department of Preventive Medicine and Biostatistics, University of Toronto, and Division of Epidemiology and Statistics, Ontario Cancer Treatment and Research Foundation, Canada. Dr Dodds is with the Keproductive Care Program of Nova Scotia, formerly of the Ontario Cancer Treatment and Research Foundation, Canada. Ms Hilditch is with the Ontario Cancer Treatment and Research Foundation Epidemiology Research Unit, University of Toronto, Canada. Address correspondence to Dr Kreiger Department of Preventive Medicine and Biostatistics, 12 Queen's Park Crescent West, 3rd Floor, McMurrich Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada. This study was funded by a grant #01692 of the Ontario Ministry of Health.     

Flavonoids and ovarian cancer risk: A case-control study in Italy

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.     

Alcohol consumption and renal cell cancer risk in two Italian case-control studies.

BACKGROUND: There is some evidence that alcohol consumption is inversely associated with renal cell cancer (RCC), but the issue is still unclear. PATIENTS AND METHODS: We investigated the relation using data from two Italian multicentric case-control studies conducted from 1985 to 2004, including a total of 1115 incident, histologically confirmed cases and 2582 controls hospitalised with acute, non-neoplastic conditions. RESULTS: Compared with non-drinkers, the multivariate odds ratios (ORs) of RCC were 0.87 [95% confidence interval (CI) 0.73-1.04] for 4 to 8 drinks per day of alcoholic beverages, with a significant inverse trend in risk (P value = 0.01). The ORs were 0.85 (95% CI 0.71-1.02) for wine, 0.84 (95% CI 0.68-1.03) for beer and 0.86 (95% CI 0.70-1.05) for spirits consumption, as compared with abstainers. No trend in risk of RCC emerged with duration (P value = 0.94) and age at starting alcohol consumption (P value = 0.81). Results were consistent in men and women, as well as in strata of age, smoking and body mass index. CONCLUSIONS: This pooled analysis found an inverse association between alcohol drinking and RCC. Risks continued to decrease even above eight drinks per day (i.e. >100 g/day) of alcohol intake, with no apparent levelling in risk.     

Regular use of analgesics is a risk factor for renal cell carcinoma.

Phenacetin-based analgesics have been linked to the development of renal pelvis cancer and renal cell carcinoma (RCC). The relationship between non-phenacetin types of analgesics and kidney cancer is less clear, although laboratory evidence suggests that these drugs possess carcinogenic potential. A population-based case-control study involving 1204 non-Asian RCC patients aged 25-74 and an equal number of sex-, age- and race-matched neighbourhood controls was conducted in Los Angeles, California, to investigate the relationship between sustained use of analgesics and risk of RCC according to major formulation categories. Detailed information on medical and medication histories, and other lifestyle factors was collected through in-person interviews. Regular use of analgesics was a significant risk factor for RCC in both men and women (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4-1.9 for both sexes combined). Risks were elevated across all four major classes of analgesics (aspirin, non-steroidal anti-inflammatory agents other than aspirin, acetaminophen and phenacetin). Within each class of analgesics, there was statistically significant increasing risk with increasing level of exposure. Although there was some minor variability by major class of formulation, in general individuals in the highest exposure categories exhibited approximately 2.5-fold increase in risk relative to non- or irregular users of analgesics. Subjects who took one regular-strength (i.e. 325 mg) aspirin a day or less for cardiovascular disease prevention were not at an increased risk of RCC (OR = 0.9, 95% CI = 0.6-1.4).     

Immunotherapy for renal cell cancer in the era of targeted therapy

Until recently, cytokine therapy has been the only validated option for patients with advanced renal cancer. IFN-α is one of very few treatments that have demonstrated improved median survival compared with the appropriate control. In patients with synchronous metastases at diagnosis, debulking nephrectomy prior to interferon, further improves overall survival. High-dose IL-2 appears to be able to cure a small percentage of highly selected patients. There is potential to further improve patient selection for these options. The demonstrated value of cytokines should not be overlooked in the rush to use new drugs. In the adjuvant setting, vaccine therapy has provided the only systemic approach that has any promise. New insights into the complexities of the immune system at the molecular level, as well as the ingenuity and enthusiasm of immunotherapists, will undoubtedly lead to continuing attempts to identify and overcome obstacles to achieve the grail of human tumor rejection in clinical practice. Targets within the immune regulatory system and the use of vaccines as targeting agents may bring together the fields of immunotherapy and targeted therapy in the near future.