Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer.
BACKGROUND
The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.


METHODS
We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided.


RESULTS
Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P(trend) = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P(trend) = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P(trend) = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile.


CONCLUSIONS
Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.
Albanes
Demetrius
D
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rm 3044, Bethesda, MD 20892-7242, USA. daa@nih.gov
Weinstein
Stephanie J
SJ
Wright
Margaret E
ME
Männistö
Satu
S
Limburg
Paul J
PJ
Snyder
Kirk
K
Virtamo
Jarmo
J
D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015992:Body Mass Index; D016022:Case-Control Studies; D005215:Fasting; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007120:Immunochemistry; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D016015:Logistic Models; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013002:Somatomedins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D007328:Insulin; D013002:Somatomedins
Br J Cancer. 2002 Sep 23;87(7):726-8
12232754
Epidemiol Rev. 2007;29:88-97
17478439
Hum Mol Genet. 2010 Aug 1;19(15):3089-101
20484221
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2056-62
17119028
Curr Opin Urol. 2005 May;15(3):167-71
15815193
J Natl Cancer Inst. 2003 Jan 1;95(1):67-71
12509402
N Engl J Med. 1994 Apr 14;330(15):1029-35
8127329
Horm Metab Res. 2003 Nov-Dec;35(11-12):694-704
14710348
Ann Epidemiol. 1994 Jan;4(1):1-10
8205268
Int J Cancer. 2007 Jun 15;120(12):2678-86
17278097
Biochem Pharmacol. 2002 Jun 1;63(11):1921-35
12093468
J Cell Sci. 2001 Aug;114(Pt 16):2903-10
11686294
J Natl Cancer Inst. 2000 Dec 6;92(23):1910-7
11106682
Urology. 2004 Feb;63(2):253-8
14972466
J Clin Endocrinol Metab. 1994 Oct;79(4):1173-6
7962291
Mol Cancer. 2003 Jan 06;2:4
12556242
Eur J Cancer. 2005 Dec;41(18):2887-95
16243513
Diabetologia. 2004 Jun;47(6):1071-8
15164171
Nat Genet. 2008 Mar;40(3):310-5
18264096
Cancer. 2005 Jan 1;103(1):76-84
15540247
Int J Oncol. 2001 Apr;18(4):683-7
11251161
Arch Physiol Biochem. 2009 May;115(2):86-96
19485704
Lancet Oncol. 2008 Nov;9(11):1039-47
18835745
JAMA. 2005 Dec 14;294(22):2872-8
16352795
Ann Intern Med. 2008 Oct 7;149(7):461-71, W83-8
18838726
J Natl Cancer Inst. 2008 Feb 6;100(3):170-83
18230794
Clin Gastroenterol Hepatol. 2006 Dec;4(12):1514-21
17162243
Am J Epidemiol. 1988 Sep;128(3):655-66
2458036
Cancer Causes Control. 2007 Jun;18(5):493-503
17450441
Prostate. 2009 Jan 1;69(1):33-40
18785179
Diabetologia. 1985 Jul;28(7):412-9
3899825