Michael Reger

MPH, PhD(c)

Indiana University - Indianapolis

Doctoral Student

PLCO (Learn more about this study)

PLCO-48

Oct 17, 2013

Phytoestrogen intake and the risk of total and advanced prostate cancer

Prostate cancer is the most common form of cancer and the second leading cause of cancer mortality among American men [1]. Non-modifiable factors have been established that increase risk of prostate cancer (age, ethnicity, and family history [2]); however the identification of modifiable factors for prostate cancer prevention would have a greater impact on the alleviation of the prostate cancer disease burden. A factor not yet definitely explored is the intake of dietary phytoestrogens in the U.S. population and the resulting impact on prostate cancer incidence and mortality.

Phytoestrogens are a group of non-steroidal plant metabolites that can induce biologic responses due to their structural similarity to 17β-estradiol and the resulting ability to bind to estrogen receptors. One of the principle classes of phytoestrogens is isoflavones, which are found mainly in soy products, legumes, and chickpeas [3]. Isoflavones found in soy products include genistein, daidzein, and glycitein [4]. Health benefits have been associated with phytoestrogen intake, including a lowered risk of heart disease, breast cancer, and osteoporosis [5], but experimental evidence conducted using rat models suggesting an increased intake of phytoestrogens may decrease the risk of prostate cancer have not been adequately explored [6, 7]. A meta-analysis of placebo-controlled clinical studies showed no effects of isoflavones on reproductive hormone levels in men; however most of the included studies had major flaws including a small number of subjects and abbreviated follow-up [8]. To this point, few epidemiologic studies have examined the association between phytoestrogen intake and prostate cancer risk, notably, the differences in risk of total prostate cancer and advanced prostate cancer with the association of phytoestrogen intake. Studies conducted in Japan, a country which demonstrates a similar incidence of latent prostate cancer compared to Western countries, show a lower mortality rate due to prostate cancer. Further, high concentrations of phytoestrogens in the urine of Japanese men suggest that lower mortality due to prostate cancer could be caused by the effect of phytoestrogens, specifically the inhibition of growth of latent cancers [9].

The study design for this project utilizes a nested case-control study based on the PLCO screening cohort and will include both high and low-grade cancer cases and controls. Statistical analysis will compare groups using chi-square, t-test, and multivariate analysis to adjust for confounding variables. The hypothesis of this study is that phytoestrogen intake is inversely associated with total and advanced prostate cancer risk, the latter being a novel but biologically plausible hypothesis not yet explored by epidemiologic studies.

There is a critical need to explore the association between prostate cancer and phytoestrogen intake. The establishment of an inverse risk association between prostate cancer and increased phytoestrogen intake could open two new avenues of prevention: primary prevention of new prostate cancer cases and secondary prevention from slowing the rate of progression of latent prostatic neoplasms to more advanced cases of the disease. This approach is both feasible and cost-effective since increasing phytoestrogen levels can be accomplished simply through the consumption of soy-based products [3].

Aim 1: The primary aim of this study is to evaluate the association between dietary intake of phytoestrogens and the risk of total prostate cancer.

Aim 1 Hypothesis: Increased dietary intake of phytoestrogens is associated with a statistically significant decreased risk of total prostate cancer.

Aim 2: To evaluate the association between dietary intakes of phytoestrogens and the risk of advanced prostate cancer.

Aim 2 Hypothesis: Increased dietary intake of phytoestrogens is associated with a statistically significant decreased risk of advanced prostate cancer.

Aim 3: To differentiate between the risks of prostate cancer associated separately with the intake of the two main phytoestrogens, genistein or daidzein

Aim 3 Hypothesis: Genistein intake is associated with a greater decreased risk of prostate cancer compared to daidzein intake, but both isoflavones will show statistically significant decreased risk.

Dietary intake of genistein and daidzein will be estimated from the baseline and third year Dietary Questionnaire and Dietary History Questionnaire.

Dietary intakes of genistein and daidzein will be divided into quintiles with the lowest quintile as the reference group. Confounders to be adjusted for in the regression models may include age, race, BMI, physical activity, smoking, alcohol, diabetes, and dietary intake of fat. Separate analyses will be conducted for advanced (defined as Stage III or IV) and non-advanced prostate cancers [10].