Does an apple a day keep the oncologist away?
前列腺液中的主要成分中除了蛋白质、各种酶类、有机物外，还含有许多的微量元素，其中锌占大多数。已有报告，人的前列腺组织中的锌含量远高于机体其他组织，有人测定前列腺液中锌含量为720微克/dl，而其它组织中锌含量仅为80微克/dl。那么锌在前列腺组织中到底起什么作用呢?国外通过一项实验研究发现前列腺液中含有一定量的抗菌成分，进一步研究证明这种抗菌成分的物质是一种含锌蛋白，其主要成分是锌，并影响炎细胞的吞噬功能，其抗菌作用与青霉素相似，故把这一抗菌成分称之为前列腺液抗菌因子。并且发现在慢性前列腺炎时，锌含量明显降低并难以提高。
通过研究结果发现，正常前列腺液锌含量为567.5±49.4微克/毫升，非细菌性前列腺炎患者为324.5±34.9微克/毫升，细菌性前列腺炎患者为135.6±28.1微克/毫升，结果证实炎症时的前列腺液锌含量明显降低，并且细菌性的锌含量更为低下，而经过用我们研制的中药前列腺汤治疗后，随着前列腺炎症的改善或治愈，锌含量也可逐渐恢复正常，说明锌与慢性前列腺炎的发病及转归有明确的相关性。
由于锌在血液和前列腺液中之含量与前列腺抗菌杀菌能力有关，所以采用含锌的药物来治疗慢性前列腺炎，其药物能否有效地被吸收，以及其适当剂量的正确掌握将是一件十分重要的事。这是因为前列腺内锌含量过高有阻止中性和巨噬细胞的作用，降低这些细胞的活力，有碍白细胞发挥正常抗菌作用。国外有的临床医学研究人员发现苹果汁对锌缺乏症具有惊人疗效，这项研究就是“苹果疗法”。
慢性前列腺炎患者除前列腺液的含锌量减少以外，尚可有皮肤发炎、脱发等给患者带来不少烦恼的症状。与过去常用的含锌药物疗法相比，苹果汁比含锌高的药物更具有疗效，且具有安全、易消化吸收，并为患者所欢迎、易接受的特点。疗效与苹果汁浓度成正比，越浓疗效越佳。故慢性前列腺炎的患者经常食用一些苹果是一种非常有益的饮食疗法。作为一种简便易行的治疗手段，“苹果疗法”容易被广大的前列腺炎患者接受应用。
摘自《前列腺防治指南》
Does an apple a day keep the oncologist away?
S. Gallus1,*, R. Talamini2, A. Giacosa3, M. Montella4, V. Ramazzotti5, S. Franceschi7, E. Negri1 and C. La Vecchia1,6
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: [email]gallus@marionegri.it[/email]
Abstract
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Abstract
Introduction
Patients and methods
Results
Discussion
References
Background: Apples have commonly been described as a healthy food. To understand better their role on risk of cancer at several sites, we analyzed data from multicenter case–control studies conducted between 1991 and 2002 in Italy.
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) 0.62–1.00] for cancers of the oral cavity and pharynx, 0.75 (95% CI 0.54–1.03) for oesophagus, 0.80 (95% CI 0.71–0.90) for colorectum, 0.58 (95% CI 0.44–0.76) for larynx, 0.82 (95% CI 0.73–0.92) for breast, 0.85 (95% CI 0.72–1.00) for ovary and 0.91 (95% CI 0.77–1.07) for prostate.
Conclusion: This investigation found a consistent inverse association between apples and risk of various cancers.
Key words: cancer, case–control study, diet, fruit, risk factor
Introduction
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Abstract
Introduction
Patients and methods
Results
Discussion
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Reviewing literature until 1997, the World Cancer Research Fund [1] reported an evidence of a protective effect of fruit on cancers of the oral cavity and pharynx, oesophagus, lung and stomach, a probable evidence on cancers of larynx, breast, pancreas and bladder, and a possible evidence for ovarian, endometrial, cervical and thyroid cancer. Likewise, an International Agency for Research on Cancer (IARC) Working Group [2] concluded that fruit reduces the risk of cancers of the oesophagus, stomach and lung, and possibly of the oral cavity, pharynx, colorectum, larynx, kidney and urinary bladder. However, the issue is still open to discussion and widely debated [3], particularly after recent findings from cohort studies that showed no association between fruit intake and risk of cancer [4, 5], including the cancers of the breast [6] and of the prostate [7].
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 [8–11], 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 case–control study from China, based on almost 1500 cases, also found a reduction of breast cancer risk across subsequent quintiles of apple intake [14]. A case–control 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 case–control studies conducted in Italy, including detailed information on several fruit items, as well as on a large number of potential confounding factors.
Patients and methods
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Patients and methods
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Case–control studies on several neoplasms have been conducted between 1991 and 2002 in various regions of northern, central and southern Italy, and have been described in detail elsewhere [19–26]. The studies included 598 patients with incident, histologically confirmed cancers of the oral cavity and pharynx [19], 304 with squamous cell oesophageal cancer [20], 1953 with cancer of the colorectum (1225 of the colon and 728 of the rectum) [21, 22], 460 of the larynx [23], 2569 of the breast [24], 1031 of the ovary [25] and 1294 of the prostate [26]. The comparison group included 6629 patients (3094 men, 3535 women) admitted to the same network of hospitals as cases for acute, non-neoplastic diseases. Twenty-four per cent of controls were admitted for traumas, 31% for other non-traumatic orthopaedic conditions, 17% for acute surgical disorders and 28% for miscellaneous other illnesses. Interviews were conducted in hospital using the same structured questionnaire, including information on socio-demographic factors, anthropometric variables, tobacco and alcohol consumption, other lifestyle habits and physical activity. For the present analysis, we compared cases with corresponding controls of each study. Subjects' usual diet before diagnosis (or hospital admission) was investigated using a validated 78-item food frequency questionnaire [27], which included a specific question on weekly consumption of apples. One portion was set as one medium-sized apple (166 g). Response rate was over 95% for both cases and controls.
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.
Results
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Table 1 gives the distribution of cases of various cancer types considered and controls according to age and sex.
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Table 1. Distribution of cases with selected cancers and corresponding controls according to age and sex; Italy, 1991–2002
Table 2 shows the distribution of cases and controls according to the frequency of consumption of apples, and the corresponding multivariate ORs. Compared with subjects reporting consumption of <1 apple/day, the multivariate ORs for those reporting 1 apple/day were 0.79 for cancers of the oral cavity and pharynx, 0.75 for oesophagus, 0.80 for colorectum, 0.58 for larynx, 0.82 for breast, 0.85 for ovary and 0.91 for prostate. Corresponding estimates after further allowance for other fruit consumption were 0.82 for cancers of the oral cavity and pharynx, 0.78 for oesophagus, 0.70 for colorectum, 0.59 for larynx, 0.76 for breast, 0.76 for ovary and 0.93 for prostate.
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Table 2. Distributiona of cases with selected cancers and corresponding controls according to consumption of apples; Italy, 1991–2002
Table 3 considers ORs for consumption of apples in strata of age, total calorie intake, and vegetable consumption. The estimates were similar across strata of the considered covariates for each cancer site. Further stratification for smoking habit and body mass index led to similar patterns.
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Table 3. Odds ratios (OR) of selected cancers and corresponding 95% confidence intervals (CI) for consumption of 1 versus <1 apple/day in strata of age, total energy intake and vegetable consumption; Italy, 1991–2002
Discussion
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Apples are a source of several phytochemicals, including flavonoids (in particular, catechins and flavonols) and phenolic acids [8–10]. When compared with other commonly consumed fruits, apples had the second highest level of antioxidant activity (after cranberries) and phenolic compounds, and the highest level of free phenolic compounds [10]. Many phytochemicals have been shown to be biologically active and may interact to protect against cancer. Experimental studies have provided evidence for the beneficial action of flavonoids on multiple cancer-related biological pathways (carcinogen bioactivation, cell-signaling, cell cycle regulation, angiogenesis, oxidative stress, inflammation) [28]. Moreover, several epidemiological studies found inverse associations between these phytochemicals and cancers of the breast [29], stomach [30] and lung [8, 9].
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 case–control 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 case–control 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.
Acknowledgements
This work was conducted with contribution of the Italian Association for Cancer Research, the Italian League Against Cancer and the Italian Ministry of Education (COFIN 2003).
Received for publication March 21, 2005. Revision received May 5, 2005. Accepted for publication June 28, 2005.
References
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