Insulin, the insulin-like growth factor axis, and mortality in patients with nonmetastatic colorectal cancer.
OBJECTIVE
Obesity, sedentary lifestyle, and Western dietary pattern have been linked to increased risk of cancer recurrence and mortality among patients with surgically resected colorectal cancer. Excess energy balance leads to increased circulating insulin and depressed levels of circulating insulin-like growth factor binding protein (IGFBP) -1, which promote cancer cell growth in preclinical models.


METHODS
Among 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3.


RESULTS
Compared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors.


CONCLUSIONS
Among patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection.
Wolpin
Brian M
BM
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. bwolpin@partners.org
Meyerhardt
Jeffrey A
JA
Chan
Andrew T
AT
Ng
Kimmie
K
Chan
Jennifer A
JA
Wu
Kana
K
Pollak
Michael N
MN
Giovannucci
Edward L
EL
Fuchs
Charles S
CS
D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000378:metabolism; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D013002:Somatomedins / Q000378:metabolism*
D002096:C-Peptide; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I