Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
OBJECTIVE
A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism.


METHODS
We prospectively examined the diabetes-prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.


RESULTS
During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively).


CONCLUSIONS
In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.
Leitzmann
Michael F
MF
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA. leitzmann@nih.gov
Ahn
Jiyoung
J
Albanes
Demetrius
D
Hsing
Ann W
AW
Schatzkin
Arthur
A
Chang
Shih-Chen
SC
Huang
Wen-Yi
WY
Weiss
Jocelyn M
JM
Danforth
Kim N
KN
Grubb
Robert L
RL
Andriole
Gerald L
GL
D000368:Aged; D015992:Body Mass Index; D016001:Confidence Intervals; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000473:pathology; D051517:Digital Rectal Examination / Q000379:methods; D004812:Epidemiologic Methods; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009043:Motor Activity; D015337:Multicenter Studies as Topic; D016017:Odds Ratio; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D047368:Tumor Burden; D014481:United States / Q000453:epidemiology
D017430:Prostate-Specific Antigen