1 Istituto di Ricerche Farmacologiche Mario Negri, Milan; 2 Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, 33081 Aviano; 3 Gastroenterology and Nutrient Unit, National Institute for Cancer Research, Genoa; 4 Servizio di Epidemiologia e Prevenzione, Istituto Tumori Fondazione Pascale, Naples; 5 Servizio Integrato di Epidemiologia e Sistemi Informativi, Istituto Nazionale Tumori "Regina Elena", Rome; 6 Infection and Cancer Epidemiology Group, International Agency for Research on Cancer, Lyon, France; 7 Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, 20133 Milan, Italy
* Correspondence to: S. Gallus, Sc.D., Laboratory of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, 62, 20157 Milan, Italy. Tel: +39-02-39014526; Fax: +39-02-33200231/39001916; E-mail: gallus{at}marionegri.it
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Abstract |
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Patients and methods: The studies included 598 patients with incident cancers of the oral cavity and pharynx, 304 of the oesophagus, 460 of the larynx, 1953 of the colorectum, 2569 of the breast, 1031 of the ovary and 1294 of the prostate. The comparison group included a total of 6629 patients admitted to the same network of hospitals as cases for acute, non-neoplastic diseases. Multivariate odds ratios (OR) were obtained with allowance for age, sex, study center, education, body mass index, tobacco smoking, alcohol drinking, total energy intake, vegetable consumption and physical activity.
Results: Compared with subjects reporting consumption of <1 apple/day, the ORs for 1 apple/day were 0.79 [95% confidence interval (CI) 0.621.00] for cancers of the oral cavity and pharynx, 0.75 (95% CI 0.541.03) for oesophagus, 0.80 (95% CI 0.710.90) for colorectum, 0.58 (95% CI 0.440.76) for larynx, 0.82 (95% CI 0.730.92) for breast, 0.85 (95% CI 0.721.00) for ovary and 0.91 (95% CI 0.771.07) for prostate.
Conclusion: This investigation found a consistent inverse association between apples and risk of various cancers.
Key words: cancer, casecontrol study, diet, fruit, risk factor
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Introduction |
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Apples are a fruit of specific interest, since they are cheap and easy to store and transport, and thus are the most frequently consumed fruit, at least in Italy. Among the studies analyzing the association between consumption of apples and cancer risk, a favourable effect was reported on lung cancer [811
], and a pooled analysis of cohort studies including more than 350 000 women and over 7000 cases of breast cancer, found a non-significant 3% reduction in breast cancer risk per 100 g/day intake [12
, 13
]. A population-based casecontrol study from China, based on almost 1500 cases, also found a reduction of breast cancer risk across subsequent quintiles of apple intake [14
]. A casecontrol study from Uruguay found an inverse relation between apple consumption and colorectal cancer [15
], one from Southern India with oral cancer [16
] and another one from Sweden with renal cancer risk [17
]. Moreover, a prospective study of Swedish women found a non-significant inverse association between apple consumption and renal cell cancer [18
].
To understand better the role of apples on risk of cancer at several sites, we considered data from a large and integrated network of casecontrol studies conducted in Italy, including detailed information on several fruit items, as well as on a large number of potential confounding factors.
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Patients and methods |
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Odds ratios (OR), and the corresponding 95% confidence intervals (CI), for consumption of apples were derived by unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, body mass index, total energy intake, vegetable consumption and physical activity. In order to disentangle the role of apples on the risk of various cancers considered, we also allowed for other fruit intake.
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Results |
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Discussion |
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Vitamin C in apples accounts for only 0.4% of the total antioxidant activity, suggesting that most of the antioxidant activity of fruit and vegetables may come from flavonoids and phenolics in apples [31, 32
]. However, cold-storage times can strongly affect the antioxidant activity and potential anticancer properties of apples [33
].
Apples may simply represent a non-specific indicator of a healthy diet. However, even after further allowance for consumption of vegetables and other fruit, the association with apples did not change, and became even stronger for some cancer sites.
Some cohort studies, including the Nurses' Health Study and the EPIC cohort, found no association between intake of fruit and risk of cancer in general [4, 5
], cancer of the breast [6
] and of the prostate [7
]. Although cohort studies are generally considered less prone to various sources of bias (mainly recall bias) [4
, 5
], they may have less detailed information on specific aspects of diet on each subject [34
], compared with casecontrol studies. However, in our studies total fruit intake was not significantly associated with cancers of the colorectum [21
, 22
], breast [22
, 24
], ovary [25
] and prostate [26
]. Thus, the present findings are not in contrast with those from the recent cohort studies [4
7
] on total fruit intake.
This study has some limitations and several strengths of hospital-based casecontrol studies. Cases and controls were interviewed in the same hospitals, came from the same geographic area and were asked about their dietary habits during the 2 years before cancer diagnosis or hospital admission. With reference to selection bias, the findings of this study cannot be attributed to selectively higher response rate of health conscious controls [5], since participation was practically complete for both cases and controls. Moreover, the strengths of the study include the large number of subjects, the satisfactory validity and reproducibility of the food frequency questionnaire [27
, 35
], and the possibility of allowance for a large number of potential confounding factors, including total energy intake. Indeed, allowance for other fruit and total energy intake strengthened the inverse associations for several cancer sites.
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Acknowledgements |
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Received for publication March 21, 2005. Revision received May 5, 2005. Accepted for publication June 28, 2005.
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References |
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