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. © 2007 Wiley-Liss, Inc.
Renal cell carcinoma (RCC), the major histologic type of kidney cancer, is still relatively uncommon, but has been rising steadily in incidence in western and many other countries around the world.1 Cigarette smoking, obesity and family history of kidney cancer are established risk factors, but they explain only part of cases.1, 2 Several epidemiological studies reported that diet is related to RCC. Although the role of specific foods or nutrients is still controversial,1 the effect of fruit and vegetable consumption seems to be favorable3, 4, 5, 6 while cereals consumption seems to be detrimental on RCC risk.7 Among potential anticarcinogens that are found in fruits and vegetables, various studies considered vitamins C and E,4, 8, 9 while available information on dietary fibre and RCC risk is scanty. In fact, the role of dietary fibre in the etiology of RCC was considered in only 2 previous case-control studies.5, 10
To our knowledge, no study investigated the role of dietary fibre on RCC in depth, taking into account different types of fibre as well as their dietary sources, and no data are available from southern European populations, which share the feature of the peculiar Mediterranean diet, i.e., a diet particularly rich in plant foods, fresh and varied fruit and with high consumption of cereals.11
This prompted us to analyse the role of various dietary fibres in the etiology of RCC in a multicentre case-control study, conducted in Italy.
Material and methods
A case-control study on RCC was conducted between 1992 and 2004 in 4 Italian areas, including the greater Milan area and the provinces of Udine and Pordenone in northern Italy, the province of Latina in central Italy and the urban area of Naples in southern Italy. Cases were 767 patients (494 men and 273 women) under age 79 years (median age 62, range 24–79 years) with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas.8
Controls were 1,534 subjects (988 men and 546 women) under age 79 years (median age 62, range 22–79 years), admitted to the same hospitals as cases for a wide spectrum of acute non-neoplastic conditions, unrelated to known risk factors for RCC nor to long-term diet modification. Controls were matched with cases by study centre, sex and quinquennia of age, with a case to control ratio of 1:2. Among controls, 26% were admitted for traumas, 32% for other orthopaedic disorders, 14% for surgical conditions and 27% for various other illnesses. Less than 5% of both cases and controls contacted refused to participate.
The same questionnaire, structured in 12 sections, was used in all study centres. It was administered by centrally trained interviewers during the subject's hospital stay and included information on personal characteristics and lifestyle habits, a problem-oriented medical history and history of cancer in 1st-degree relatives, anthropometric measures and aspirin use. An interviewer-administered food frequency questionnaire (FFQ) was utilized to assess the usual diet during the 2 years preceding diagnosis (for cases) or hospital admission (for controls). The FFQ included 78 foods, food groups or dishes divided into 6 sections: (i) bread, cereals, 1st courses; (ii) second courses (i.e., meat, fish and other main dishes); (iii) side dishes (i.e., vegetables); (iv) fruits; (v) sweets, desserts and soft drinks; (vi) milk, hot beverages and sweeteners. For a few seasonal vegetables and fruits, consumption in season and the corresponding duration were elicited. At the end of each section, 1 or 2 open questions were used to include foods that were not in the questionnaire, but were eaten at least once per week. The FFQ allowed to estimate the intake of total energy as well as of selected nutrients, using Italian food composition databases integrated with other sources when needed.12
Dietary fibre was derived using the Englyst method.13, 14 A modification of the procedure permitted to measure cellulose separately from insoluble noncellulose polysaccharides, while values for lignin were provided separately. We did not include resistant starch in the computation of total fibre, because the amount depends on how each food is processed and consumed,15 and related food composition tables were not available. Fibre intake was also divided according to the food from which it originated (i.e., vegetable, fruit or cereal).
The FFQ was satisfactorily reproducible16 and valid.17 Reproducibility was evaluated by means of the Pearson product–moment correlation coefficient (r) between log-transformed intake of fibre calculated from 2 questionnaires administered at intervals of 3–10 months. Pearson correlation coefficient for reproducibility for fibres was 0.67.16 Validity was estimated comparing the FFQ with two 7-day diaries, by means of the Pearson product–moment correlation coefficient between intake of fibre computed from the FFQ and the average value derived from the two 7-day diary records. After allowance for energy intake, age, sex and study centre, the Pearson correlation coefficient for validity for fibre intake was 0.57.17
The odds ratios (OR) of RCC and the corresponding 95% confidence intervals (CI) were calculated using conditional multiple logistic regression models conditioned on study centre, sex and quinquennia of age, and adjusted for year of interview, years of education, family history of kidney cancer in 1st-degree relatives, tobacco smoking, alcohol drinking, body mass index (BMI) and occupational physical activity at age 30 years. Allowance was also made for total energy intake, using the residual method.18 With a sample size of about 750 cases and 1,500 controls, our study had 80% power to detect a 25% reduced risk (i.e., an OR ≤ 0.75) for the highest compared with the lowest quintile of fibre intake (α = 0.05).
Table I gives the distribution of RCC cases and controls and the multivariate ORs (in quintiles and continuously) for various types of dietary fibre and their food source. As referred to the lowest quintile of intake, the ORs for the highest quintile of intake were 1.04 for total dietary fibre, 1.07 for soluble NCP, 0.92 for total insoluble fibre, 0.84 for cellulose, 0.93 for insoluble NCP and 1.14 for lignin. There was no trend in risk with dose for any type of fibre. The continuous OR for an increase in intake equal to the difference between the 80th and the 20th percentile ranged between 0.90 (95% CI: 0.78–1.04) for cellulose and 1.06 (95% CI: 0.93–1.21) for lignin. With reference to the sources of fibres, we found an inverse association with vegetable fibre (OR = 0.73, 95% CI: 0.54–0.97, for the highest quintile of intake vs. the lowest), and no significant association with fruit (OR = 1.01, 95% CI: 0.76–1.34) and grain fibre (OR = 1.26, 95% CI: 0.92–1.73).
Table I. Odds Ratios1 (OR) and 95% Confidence Intervals (CI) of Renal Cell Carcinoma According to the Intake of Various Types of Fibre and Their Food Source, Italy 1992–2004
|Total (Englyst) fibre||157||307||161||306||140||307||146||307||163||307||0.004||0.94 (0.82–1.08)|
| OR (95% CI)||14||1.03 (0.78–1.37)||0.93 (0.69–1.24)||0.92 (0.69–1.23)||1.04 (0.78–1.40)|
|Soluble NCP||158||306||164||307||140||307||135||308||170||306||0.01||0.98 (0.85–1.13)|
| OR (95% CI)||14||1.02 (0.77–1.36)||0.88 (0.66–1.83)||0.84 (0.62–1.13)||1.07 (0.80–1.44)|
|Total insoluble fibre||162||307||145||307||153||307||159||306||148||307||0.11||0.92 (0.80–1.05)|
| OR (95% CI)||14||0.94 (0.71–1.25)||0.97 (0.73–1.29)||0.99 (0.74–1.32)||0.92 (0.68–1.23)|
| OR (95% CI)||14||0.89 (0.68–1.18)||0.85 (0.64–1.13)||0.88 (0.66–1.16)||0.84 (0.63–1.12)|
|Insoluble NCP||149||306||144||307||158||307||174||308||142||306||0.03||0.95 (0.84–1.06)|
| OR (95% CI)||14||0.95 (0.71–1.27)||1.06 (0.79–1.41)||1.15 (0.86–1.54)||0.93 (0.69–1.26)|
| OR (95% CI)||14||0.94 (0.70–1.27)||1.21 (0.91–1.62)||0.96 (0.71–1.30)||1.14 (0.84–1.54)|
|Vegetable fibre||185||307||145||306||144||308||156||306||137||307||3.45||0.84 (0.73–0.97)|
| OR (95% CI)||14||0.80 (0.60–1.05)||0.77 (0.58–1.02)||0.83 (0.63–1.09)||0.73 (0.54–0.97)|
|Fruit fibre||167||307||149||306||149||307||143||307||159||307||0.007||0.98 (0.86–1.12)|
| OR (95% CI)||14||0.94 (0.71–1.24)||0.95 (0.71–1.25)||0.88 (0.66–1.17)||1.01 (0.76–1.34)|
|Grain fibre||125||307||122||306||177||308||179||307||164||306||4.97*||1.05 (0.95–1.15)|
| OR (95% CI)||14||0.99 (0.73–1.35)||1.47 (1.09–1.99)||1.41 (1.05–1.91)||1.26 (0.92–1.73)|
Table II considers the relationship between vegetable fibre intake and RCC risk in separate strata of sex, age, education, BMI, smoking habits, alcohol drinking, occupational physical activity and total energy intake. No appreciable nor significant heterogeneity emerged across these strata, although the ORs appeared to be, if anything, lower in women (OR = 0.63) than in men (OR = 0.95) and in subjects with age below 60 (OR = 0.74) than in those with age above 60 years (OR = 0.91). We also considered the relationship between total fibre intake and RCC risk in separate strata of sex and age. The continuous ORs were 1.00 (95% CI: 0.85–1.19) for men and 0.82 (95% CI: 0.64–1.05) for women, 0.89 (95% CI: 0.72–1.10) for subjects with age above 60 years and 0.98 (95% CI: 0.81–1.17) for those with age above 60 years (data not shown). We found no appreciable nor significant heterogeneity across these strata, also for all the other types and sources of fibres considered.
Table II. Odds Ratios1 (OR) and 95% Confidence Intervals (CI) of Renal Cell Carcinoma, According to Vegetable Fibre Intake, in Strata of Selected Covariates, Italy, 1992–2004
| Men||0.95 (0.80–1.12)|
| Women||0.63 (0.47–0.83)|
| <60||0.74 (0.58–0.94)|
| ≥60||0.91 (0.76–1.10)|
| <11||0.90 (0.76–1.07)|
| ≥11||0.71 (0.52–0.97)|
|Body mass index (kg/m2)|
| <25||0.83 (0.71–0.98)|
| ≥25||0.91 (0.59–1.39)|
| Never smokers||0.97 (0.78–1.21)|
| Current smokers||0.90 (0.68–1.19)|
| Ex smokers||0.70 (0.52–0.92)|
| Never drinkers||0.84 (0.55–1.29)|
| Current drinkers||0.89 (0.76–1.05)|
| Ex drinkers||0.53 (0.25–1.01)|
|Occupational physical activity at age 30|
| Mainly standing/sitting||0.85 (0.66–1.11)|
| Intermediate||0.86 (0.67–1.11)|
| Heavy/strenuous||0.86 (0.66–1.13)|
|Total energy intake2 (kcal/die)|
| I (lowest)||0.91 (0.68–1.22)|
| II||0.82 (0.63–1.07)|
| III (highest)||0.86 (0.68–1.09)|
In this study, based on one of the largest case-control investigations on RCC, total dietary fibre intake was not related to the risk of RCC in this southern European population. Thus, our results are in broad agreement with those from 2 previous studies conducted in American, Australian and northern European populations. In the international renal cell cancer study, conducted in Australia, Denmark, Sweden and United States among 1,185 cases of RCC and 1,526 controls,10 the OR for the highest versus the lowest quartile of intake of total fibre was 0.87 (95% CI: 0.65–1.15). In a study conducted in Sweden among 376 cases of RCC and 350 controls,5 the corresponding OR was 0.69 (95% CI: 0.45–1.07).
Our study added original information on the role of various subtypes and food sources of dietary fibres. Only vegetable fibres were inversely related to RCC. Anyway, keeping in consideration the null association with total and various subtypes of fibres, these results may be attributed to other micronutrients found in vegetables rather than to a direct effect of fibres themselves. In fact, a protective role of vegetables and an apparent detrimental effect of grain foods on RCC was reported by several epidemiological studies.3, 4, 5, 6, 7 When we analysed vegetables and grain foods intake using the same data, we found that vegetables were inversely associated with RCC risk, whereas bread, pasta and rice were directly associated.7
Among the possible limitations of the present study, there is the use of hospital controls, whose dietary habits may differ from those of the general population.19 However, we took great care in excluding from the control group all diagnoses that might have been associated to tobacco smoking or involved long-term modifications of diet. Further, in the present study dietary intake was very similar across the 4 major diagnostic categories of controls (i.e., traumas, other orthopaedic, surgical and miscellaneous conditions). Moreover, the similar interview setting and catchment areas, and the almost complete participation of cases and controls are reassuring against any relevant selection and recall bias. Another limitation may be the problem of multiple comparisons, which can lead to chance findings. Among the strengths of the study, there are the large sample, which allowed analysis in subgroups of subjects, and the use of a validated17 and reproducible16 FFQ, which allowed a comprehensive assessment of major nutrient sources in the Italian diet. Further, total energy intake as well as major potential confounding factors—including tobacco smoking, BMI and education—were carefully accounted for in all the analyses.
The authors thank Mrs. I. Garimoldi for her editorial assistance. Dr. Carlotta Galeone was supported by a fellowship from AIRC/FIRC.