Fruit Intake and Prostate Cancer Risk

"Eat to Live, Not Live to Eat"
John H Weisburger, 2000

In developed countries, prostate cancer is the second most frequently diagnosed cancer in men. Lifetime risks of a diagnosis and death are about 16% and 3% respectively, and non-modifiable risks are age, race, family history and some less common genetic factors. Diagnosis is rare in men under 50, 70% of deaths occur after age 75, and the age-adjusted incidence rates in younger men (particularly 45-54 yrs) have been rising in most countries (including Australia) over the last 30 years, an increase that can't simply be explained by more wide-spread screening. Many diagnosed cancers are asymptomatic and either won't progress or they'll grow so slowly that in all probability people will die of other causes. This underlies why there is so much debate on screening for the disease, as positive test results can lead to much concern in individuals and families, and may also result in over-treatment that has significant and permanent unwanted effects for dubious gain. The merit of the widely-used prostate specific antigen (PSA) test is controversial, and some professional health authorities now recommend it should not be used while others believe when combined with other risk factors it can be meaningful for some age groups. If tests are conducted and they return positive results, a strategy of 'watchful waiting' can often be the most appropriate way forward.

Can anything be done to minimise risks? This question has been studied in the following recent report by a large and distinguished European research team published in The International Journal of Cancer (2017) 141, 287–297. They note the wide variation in prostate cancer incidence globally, with Westernised countries having incidence rates many times those of some other countries. However when immigrants from these countries settle in the West and adopt their lifestyles they subsequently move to the higher rates. These observations suggest modifiable environmental and lifestyle factors, (eg chronic inflammation, metabolic syndrome, dietary and others) could be relevant risk factors for the disease. Concerning diet, previous studies have produced equivocal results despite increased fruit and vegetable intake having documented preventive effects in several other cancers. The latest report considering several studies on fruit and vegetable intake and prostate cancer by the World Cancer Research Fund/American Institute for Cancer Research in 2014 stated that no conclusion could be reached on whether there was an association, but this report did not differentiate between grade and stage of the disease, and only a limited number of fruit and vegetable subtypes (namely cruciferous vegetables and tomatoes) were considered. The present authors therefore considered that a more detailed study was needed to better examine this question.

Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumour characteristics, and results obtained so far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios and confidence intervals. After an average follow-up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth (quintile), those in the highest fifth of total fruit intake had a significant 9% reduced prostate cancer risk. No associations between fruit subtypes and prostate cancer risk were observed for individual quintiles, but for citrus fruits there was a weak but significant trend across quintiles. No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumour grade and stage, with the exception of significant heterogeneity by tumour grade for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear.

This was a large study by an authoritative team. It was prospective, meaning all participants were free of the disease on entry and were then followed for a number of years. This study design avoids the problem of participants modifying their dietary intake responses if they already know they have the disease, eg by providing biased data according to their own interpretation of what could have caused it, or what they regard as conforms more closely with commendable behaviours in their society eg obese people regularly under-report their energy intake. Participants were entered from 19 centres in 8 European countries - Denmark, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK, so results likely have broad applicability for Caucasians living in developed countries. Dietary information was collected by questionnaire, and this information was subsequently checked by taking an 8% random sample of the whole study group. The vegetable category did not include potatoes and dried beans. The sub- types of fruit considered (fresh fruit only) were citrus (eg oranges, lemons), apples and pears, and bananas; other sub-types such as grapes and berries could not be properly studied because of low intake. For vegetables, the sub-groups were: cruciferous (eg broccoli, cabbage), leafy (eg spinach, lettuce), fruiting (eg tomato, sweet pepper, eggplant), tomatoes (raw, cooked, sauce) and root vegetables (e.g., carrot, beetroot). For those diagnosed with prostate cancer, the average ages at entry and diagnosis were 50 and 68 years resp. Some of their characteristics varied by fruit and vegetable consumption - eg men in the highest 20% of fruit and vegetable intake were older at recruitment and diagnosis, less likely to smoke, more likely to be diabetic, and also be shorter with a higher body mass index (BMI) and energy intake. Factors included in the analysis apart from fruit and vegetables that could possibly have influenced diagnosis were: recruitment age, recruitment centre, educational level, smoking status, marital status, diabetes, physical activity, height, BMI and total energy intake.

The authors suggested if there's a real association between fruit consumption and prostate cancer risk it might be due to the high content of vitamins (eg vitamin C) and phytochemicals (such as phenolic compounds and carotenoids) which may have anti-carcinogenic properties. Generally it is known that fruit have several times the phytochemical/antioxidant levels of vegetables and this could have contributed to the significantly different effects seen between the two. Nevertheless the authors did caution that men who have high fruit intake differ in several important respects from men with a low fruit intake, and therefore the observed associations could have been due to factors additional to those above that were not allowed for in their analysis (ie residual confounding). Given the relatively small preventive effect reported (9% decreased risk), they wisely suggest that further studies are needed to confirm their finding. However, obtaining more conclusive evidence for dietary effects on this cancer is particularly challenging given its long development time, the current inability to efficiently distinguish indolent from aggressive tumours in early stages, and its widespread prevalence which in one study was about 36% at post-mortem autopsy in US and European men aged 70-79.

We're left with the well-studied observation from migrant data that some modifiable factors contribute to onset and progress of prostate cancer, but the diversity of findings amongst studies conducted so far probably indicates that relevant factors have not yet been sufficiently identified and/or quantified, and perhaps also that diagnosis is not strongly influenced by a small number of factors or dietary components but by a combination of many. Nevertheless and despite the above, at present it would seem sensible for men to ensure they regularly include sufficient fruit in their diet, given a possibly desirable health outcome here along with those more convincingly demonstrated in other non-communicable diseases.

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