Abstract and Introduction
Abstract
The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.
Introduction
Prostate cancer is one of the most common malignancies in the Western world, and its etiology remains largely unknown. Most but not all epidemiologic studies have found milk intake during adult life to be associated with an elevated risk. The association is largely limited to advanced disease, and studies of screen-detected or early-stage disease tend to be null. This difference is important, given the substantial heterogeneity in the biologic potential of prostate cancer and the need to identify risk factors and opportunities for prevention of advanced disease.
Early-life diet may be important in the pathogenesis of prostate cancer, particularly around puberty when the prostate grows and matures. Few studies have addressed milk intake in early life and prostate cancer risk. A Swedish study found no association between early-life exposure to dairy products and risk of prostate cancer, and in the Boyd Orr cohort study, van der Pols et al. found reduced risk with increased childhood consumption of milk. Studying early-life exposure is challenging because of a lack of variation in intake patterns and the need for follow-up over many decades.
In the early and mid-20th century in Iceland, there was considerable variability in dietary habits between residential areas because of the relative isolation of some regions. A 1939 household questionnaire found that consumption of milk was 4 times higher in rural areas than in seaside villages and twice that in the capital, Reykjavik. Thus, Iceland represents a natural experiment with which to study dietary patterns in early life.
Nationwide cancer registers began to be kept in Iceland in 1955. The age-standardized incidence of prostate cancer in Iceland has increased dramatically to become one of the highest in the world: 100.6 per 100,000 men in 2004–2008 (15; http://www.cancerregistry.is). Using these population-based data sources and the well-characterized Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort, we investigated whether residency-dependent milk consumption in early life was associated with the risk of prostate cancer.