No Association of Waist Circumference and Prostate Cancer in the Cancer Prevention Study II Nutrition Cohort

The relationship between adiposity and prostate cancer risk remains unclear despite extensive study of this issue. Findings of the 2014 World Cancer Research Fund International/American institute for Cancer Research (WCRF/AICR) Continuous Update Project found convincing evidence of a positive association between body mass index (BMI; kg/m²) and advanced prostate cancer (1). However, a subsequent International Agency on Research for Cancer review found the evidence limited (2). An MRI study has shown that for men, waist circumference (WC) is the best measure of visceral adipose tissue (3), which is metabolically active and likely responsible for much of the carcinogenic risk associated with adiposity (4). Only six prospective studies have investigated the association between WC and advanced prostate cancer, four of which were included in the WCRF/AICR review (5) and two which were conducted later (6, 7). Although there was some variation in how advanced prostate cancer was defined, five found evidence of increased risk, although it was statistically significant in just two studies (5, 7). In this study, we examined the association between WC and prostate cancer incidence and mortality among men enrolled in the Cancer Prevention Study II (CPS-II) Nutrition Cohort.

Men in this analysis were participants in the CPS-II Nutrition Cohort, a prospective study of cancer incidence begun in 1992. Details of the recruitment and characteristics of this cohort have been described previously (8). On the 1997 questionnaire, participants reported weight and measured WC using a tape measure sent to them. Participants were instructed to measure their WC to the nearest quarter inch just above the navel while standing, and to avoid measuring over bulky clothing. BMI was calculated from current weight and height reported on initial enrollment in CPS-II in 1982.

Follow-up for the incidence analysis was from the date of receipt of the 1997 questionnaire to date of diagnosis of prostate cancer, death, or June 30, 2013. Follow-up for the mortality analysis was from the 1997 questionnaire receipt to date of prostate cancer death, other death, or June 30, 2103. Incident cancers were self-reported on follow-up questionnaires sent in 1999 and every 2 years thereafter and were verified through medical records or state cancer registries. Additional cancers were ascertained through linkage to the National Death Index.

Of the 73,046 men who completed the 1997 questionnaire, 26,952 were excluded for loss to follow-up, prevalent cancer, missing WC or BMI information, WC ≤20 inches, or BMI ≤18.5 k/m², leaving 46,094 men for this analysis. Of these, 5,711 were diagnosed and 416 died from prostate cancer between 1997 and 2013. High-grade prostate cancer was defined as Gleason score ≥ 8, whereas low grade included all cases with Gleason score < 8.

Quintiles for WC were defined on the basis of the distribution within the analytic cohort. Cox proportional hazards regression modeling was used to estimate the RRs and 95% confidence intervals (CI) for the association between WC and prostate cancer. Cox models were adjusted for age, race, family history of prostate cancer, history of PSA testing, history of diabetes, physical activity energy intake, education, alcohol intake, and, where indicated, BMI.

The men in this study were older (mean age 68 years) and predominantly white. As shown in Table 1, men with a larger WC were more likely to be former smokers and to have a higher BMI and total calorie intake than men with a smaller WC.

The categorical and continuous associations of WC with prostate cancer are shown in Table 2. Consistent with the categorical results, the association based on the continuous analyses was marginal for all cases (RR = 0.97; 95% CI, 0.95–1.00 per 10 cm) and significant for low-grade cases (RR = 0.95; 95% CI, 0.92–0.98 per 10 cm) before adjustment for BMI. After BMI adjustment, neither of these results were significant. No association was observed between WC and either high-grade or prostate cancer mortality regardless of adjustment for BMI. All associations were unchanged when the first 4 years of follow-up were excluded, suggesting that reverse causation did not influence these results.

We found no association between WC and high-grade prostate cancer even though we had more high-grade prostate cancer cases than the largest previous study (809 vs. 641) to report a significant result (7). One difference that might explain the disparate findings is age. The average age of the men in our study at the time of WC measurement was 68 years, whereas it ranged from 52 to 63 years in the other studies that showed positive associations (5–7). With less than 5% of the men in our study less than 60 years old, we were unable to investigate the influence of age on the WC association. Thus, additional research is needed to determine whether the association between WC and high-grade prostate cancer is affected by age.

No potential conflicts of interest were disclosed.

The views expressed here are those of the authors and do not necessarily represent the American Cancer Society or the American Cancer Society – Cancer Action Network.

Conception and design: V.L. Stevens

Development of methodology: V.L. Stevens, A.V. Patel

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): V.L. Stevens, E.J. Jacobs, A.V. Patel, S.M. Gapstur

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): V.L. Stevens, E.J. Jacobs, M.L. Maliniak, A.V. Patel

Writing, review, and/or revision of the manuscript: V.L. Stevens, E.J. Jacobs, M.L. Maliniak, A.V. Patel, S.M. Gapstur

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): M.L. Maliniak

The authors express sincere appreciation to all Cancer Prevention Study II participants and to each member of the study and biospecimen management group. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort.

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