Michael Cook

PhD

NCI, DCEG, HREB

Investigator

PLCO (Learn more about this study)

PLCO-64

Feb 3, 2014

Weight change across the adult life course in relation to total, aggressive and lethal prostate cancer

Prostate cancer is the most commonly diagnosed and prevalent nondermatologic cancer in the United States today, regardless of sex. Prevention of aggressive and lethal forms of prostate cancer is a global public health concern, with the United States and the westernized world impacted most prominently. Significant progress has been made in treating prostate cancer, yet age-standardized mortality rates have decreased by only 3% over the last two decades, lagging declines in both breast (15.3%) and colorectal (10.9%) cancer by wide margins. As a result, prostate cancer is the second leading cancer-related cause of death in the United States, trailing only lung cancer. While the majority of cases result in an indolent form of the disease, widespread PSA-screening has led to significant overdiagnosis of prostate cancer in men, and a fundamental issue is to distinguish aggressive or lethal disease at an early stage by identifying causal mechanisms that distinguish them from the more common indolent form. Additionally, prostate cancer metastasizes to the bone more than any other cancer, which is often then incurable, contributing to high mortality risks within such patient groups. Few factors or mechanisms have been casually linked to the more rare aggressive and lethal forms of prostate cancer, but environmental and lifestyle factors are hypothesized to play a potentially important etiologic role, of which anthropometric factors may be used as proxy exposures. Within the United States and Europe, it is estimated that 10–15% of all cancer-related mortality may be attributable to excess body size. While obesity and body size have been studied in detail in relation to disease states, including prostate cancer, longitudinal analyses of obesity and weight change across the adult life-course in relation to prostate cancer are scarce. The studies that have been conducted have provided inconsistent results, with some evidence that weight gain during early to middle adulthood may decrease risk of localized disease as well as increase risk of aggressive or advanced prostate cancer, while the majority of evidence supports the null hypothesis of no association. Given that recent research has indicated that exposures during early adulthood may have significant effects on prostate cancer risk, the examination of multiple time periods of exposure during the extended phase of prostate carcinogenesis—from onset of adulthood throughout the natural history of the disease—is required to more clearly define the effect of body size in relation to prostate cancer risk. Therefore, we will investigate whether body mass index and weight across the adult life-course are related to prostate cancer risks, with a primary focus on lethal and aggressive disease.

We propose to utilize the PLCO cohort to examine the association between body mass index and weight across the adult life-course and prostate cancer risk, for male participants from both the screening and the control arms of the study who responded to both the baseline and supplemental questionnaire.

Aims:
1. To assess age-specific BMI and weight in relation to prostate cancer risk, with sub-analyses of non-aggressive, aggressive and lethal disease.

2. To assess the relationship between long-term and short-weight change during the adult life-course and prostate cancer risk, with sub-analyses of non-aggressive, aggressive and lethal disease.

3. To explore potential effect modification by examining whether the associations between BMI/weight change and prostate cancer are modified by age, race, cigarette smoking, type II diabetes mellitus, family history of prostate cancer, PSA screening, physical activity (MET hours), treatment (lethal cases), and dietary factors (e.g., total energy intake).

4. To investigate whether maximum BMI attained during the life-course is associated with prostate cancer, with sub-analyses of non-aggressive, aggressive and lethal subtypes