Prostate cancer incidence rates vary 25-fold worldwide. Identifying biological factors that also vary by region may improve our understanding of prostate cancer risk factors and could inform prevention efforts.
To help in these efforts, researchers, led by Emma H. Allott, assistant professor of nutrition at the University of North Carolina at Chapel Hill Gillings School of Global Public Health, examined global differences in rates of prostate inflammation and considered how the varying rates of inflammation relate to subsequent risk for prostate cancer.
The resulting study, “Geographic differences in baseline prostate inflammation and relationship with subsequent prostate cancer risk: Results from the multinational REDUCE trial,” was published online April 18 in the journal Cancer Epidemiology, Biomarkers and Prevention. An abstract of the journal article was published April 26 on UroToday.com.
Allott says that geographic differences in prostate cancer-specific antigen (PSA) screening rates likely drive much of the global variation in incidence rates, but differences in lifestyle also may contribute.
“Lifestyle factors that vary by geographic region—including diet, smoking and medication use—may influence prostate inflammation,” Allott said. “That, in turn, could affect prostate cancer risk. Our results from the multinational REDUCE prostate cancer chemoprevention trial demonstrate, for the first time, that there are pronounced geographic differences in the prevalence of inflammation in benign prostate tissue.”
REDUCE was a four-year, double-blind and placebo-controlled prostate cancer chemoprevention trial that enrolled 7,000 non-Hispanic white men, 50-75 years of age, who were at high risk for prostate cancer. The men, from Europe, North America, South America, Australia and New Zealand, had undergone a baseline prostate biopsy, found to be negative for prostate cancer and agreed to subsequent prostate biopsies two and four years later.
For the study’s analysis, the subjects’ baseline prostate biopsy tissue underwent histologic examination by a pathologist to assess the presence of inflammation.
Allott and her colleagues examined patterns of prostate inflammation across global regions and explored the relationship between region and prostate cancer risk at the two-year biopsy mark. Given an established role for inflammation in cancer development, the researchers hypothesized that geographic differences in the prevalence of histologic prostate inflammation would be accompanied by geographic differences in prostate cancer risk.
The study authors found that the prevalence of prostate inflammation varied across the world, with higher rates in North America, Australia and New Zealand, relative to Europe. They also found that regions of the world with higher rates of prostate inflammation had lower rates of prostate cancer diagnosis on subsequent biopsy. While inflammation traditionally has been considered a risk factor for cancer, histologic assessment of inflammation does not fully capture the complexity of this biological process, which may include both pro-tumor and anti-tumor effects.
The study authors’ ongoing research, focused upon optimizing molecular assays to distinguish pro-tumor from anti-tumor inflammation, aims to improve understanding of the relationship between inflammation and prostate cancer. Current findings may point to inflammation as a potential modifiable mechanism linking lifestyle/environmental factors and prostate cancer.
The study team also included Adriana Vidal and Stephen Freedland from Cedars-Sinai Medical Center; Sarah Markt and Lorelei Mucci from the Harvard T. H. Chan School of Public Health; Daniel Moreira from the University of Illinois at Chicago; Ramiro Castro-Santamaria from GSK; and Gerald Andriole from Washington University School of Medicine.
Allott is also the Irish Cancer Society’s John Fitzpatrick Research Fellow at Trinity College, Dublin. The fellowship was established by the Irish Cancer Society, the Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health to fund an Irish scientist or clinician to undertake high-quality research into prostate cancer.