No Association between Egg Intake and Prostate Cancer Risk: A Meta-analysis

Objective: Egg consumption has been suggested to increase the risk of colorectal and some other cancers. The present study summarized and quantified the current evidence relating dietary intake of eggs and prostate cancer. Materials and methods: Literature searches were conducted to identify peer-reviewed manuscripts


Introduction
Prostate cancer is the most common cancer among men in United States.It is also one of the leading causes of cancer death among men of all races (Siegel et al., 2012).Although age and family history have been established as strong risk factors for prostate cancer, the role of individual dietary factors is not well understood.The large variation in incidence across countries may also suggest the role of lifestyle and dietary factors in its cause (Yu et al., 1991).Eggs are frequently consumed worldwide, supply substantial portions of protein, fat, retinal, riboflavin and iron.Eggs are also unique among foods, given their relatively high content of several substances, such as cholesterol, choline, biotin, and avidin.There is evidence pointing to a possible role of eggs consumption on cancer etiology.A positive association has been observed between eggs consumption and risk of colorectal cancer (Steinmetz et al., 1994).For other cancer sites, there is no established association with eggs.Several studies considered the relation between eggs intake and prostate cancer.Though most of them reported no association, results were often inconsistent.With the aim to investigate the relationship between prostate cancer and eggs consumption, we carried out a meta-analysis of epidemiological studies published up to July 2012.

No Association between Egg Intake and Prostate Cancer Risk: A Meta-analysis
Bo Xie 1 , Huadong He 2 * Medline database, using PubMed, for all studies published in English.We used the following search string in free full-text: (egg or eggs) AND (prostate or prostatic) AND (cancer or carcinoma).The reference lists of all papers of interest were checked to obtain other pertinent publications.For inclusion in this meta-analysis, studies should assess eggs intake in relation to histologically confirmed prostate cancer with informative effect estimates.Cross-sectional and ecologic analyses were excluded.
Figure 1 showed the flowchart for selection of articles.A total of 86 publications were identified in the primary search.Seventy-two articles were excluded after screening the titles and abstracts.We included 12 studies after
We reviewed all the studies and abstracted the information as follows: the name of the first author, the year of publication, study design, country, period of enrolment (case-control studies) and/or of follow-up (cohort studies), number of subjects, covariates adjusted for in the analysis, odds ratios (ORs) or relative risk (RRs) for highest vs lowest level of consumption and exposure assessment.When available, we used multivariateadjusted risk estimates.
We estimated the summary association between eggs consumption and prostate cancer incidence in case-control and cohort studies separately.Subgroup analyses were performed according to geographical regions, time of PSA screening (Using 1994 as the cutoff for after which time most men were screened for PSA).In addition, we performed analyses for the association of eggs consumption with high-stage and fatal prostate cancer.We calculated summary estimates using the fixed or random effects models depending on heterogeneity between studies.Heterogeneity between studies was assessed using the Cochrane Q test and I 2 score.We conducted sensitivity analyses by excluding each study at a time from the metaanalysis.Publication bias was assessed using the tests of Egger and Begg.Statistical significance was considered while p < 0.05.We performed all statistical analyses with Stata v.11.0 (StataCorp, College Station, TX).
A subgroup analysis was also performed according to different regions.We found that the non-significant relationships between prostate cancer and eggs consumption were consistent in all geographical areas.The pooled RR was not statistically significant before introduction of PSA test.No cohort began enrolling patients after 1994.

Advanced prostate cancer
The only cohort study (Schuurman et al., 1999) to report RR estimates based on tumor stage reported eggs consumption to have a significant negative association with high-stage prostate cancer (RR 0.70, 95% CI 0.53-0.93).

Discussion
Previous studies have suggested that eggs consumption may increase the risk of colorectal cancer and some other cancers (Steinmetz et al., 1994;Aune et al., 2009).In the present meta-analysis, we found no statistically significant positive association between high intake of eggs and risk of prostate cancer.Furthermore, our findings for lethal prostate cancer also suggested no association with high consumption of eggs.To our knowledge, this is the first meta-analysis to evaluate the relationship between them.
Several factors contributed to the stability of our findings.First, the results were generally homogeneous.No heterogeneity was detected in cohort studies but some heterogeneity in case-control studies.However, when the study (Deneo-Pellegrini et al., 2012) conducted in Uruguay with the highest effect estimates was excluded, the results for case-control studies became homogeneous, and the pooled OR was not significantly changed.Second, the findings were consistent across the subgroup analyses, regardless of regions and PSA screening.Third, for the two established risk factors, all studies included in this meta-analysis provided risk estimates adjusted for age, but only 2 case-control studies and 1 cohort study controlled for a family history of prostate cancer in their analyses.It is unlikely that is a strong confounder because a family history of prostate cancer is not strongly related to eggs consumption, it could not be a strong confounder for association for them.
A mechanistic role of eggs intake in the etiology of prostate cancer is plausible.Eggs are an important source of cholesterol and choline, both of which are highly concentrated in prostate cancer cells.Cholesterol homeostasis is disrupted in malignant cells, leading to accumulation of cholesterol, which is a precursor of androgen and may alter signaling pathways to promote cancer progression (Freeman et al., 2004;Dillard et al., 2008).Choline is essential for a variety of functions involved in cancer growth and progression.Malignant prostate cells have higher choline concentrations than do healthy cells, and choline kinase is overexpressed in prostate cancer (Glunde et al., 2006;Ramirez de Molina et al., 2008).Blood concentrations of cholesterol and choline have been positively associated with risk of advanced prostate cancer (Platz et al., 2008;Johansson et al., 2009).However, in our study, eggs consumption was associated with a lower incidence of advanced prostate cancer, and no association was observed with fatal prostate cancer, while these results need to be interpreted with caution because of the few studies available.Another plausible mechanism through which eggs could increase the risk of prostate cancer include the effect of calcium in prostatic epithelium, which was the only mineral presented a significant increased risk of prostate cancer (Gao et al., 2005;Huncharek et al., 2008).
Our study has several limitations.First, as a metaanalysis of observational data, our results are prone to recall and selection bias inherent in the original studies.Second, eggs are generally not the main focus of the included studies.Although analysis of total eggs consumption was based on many studies, fewer studies were available for the secondary outcomes of advanced and lethal disease.Also, eggs intake may include eggs prepared in a number of methods, such as fried eggs, which may increase risk of prostate cancer by higher intake of fat.Third, because of limited resources, we only searched PubMed, and collected papers in English, which may lead to publication bias, even though no significant evidence of publication bias was observed.
In conclusion, this meta-analysis of epidemiological studies provides evidence on the absence of any association between eggs intake and prostate cancer risk.Given the relatively small number of cohort studies included in this meta-analysis, larger prospective studies are needed to confirm this association in the future.

Figure 2 .
Figure 2. Pooled Results for 11 Case-control Studies of Eggs Consumption and Prostate Cancer Incidence

Table 1 . Study Characteristics of Published Cohort and Case-control Studies on Eggs Intake and Prostate Cancer
, marital status , study area, body mass index, education, ever-used multivitamin supplements in 1 yr before diagnosis/interview, area of study, and log-converted amounts for grains, fruit, vegetables, total plants, total carotenoids, folic acid, dietary fiber, conjugated linoleic acid, vitamin E, vitamin C, retinol, total fat, and linoleic acid.