Interactions between plasma levels of 25-hydroxyvitamin D, insulin-like growth factor (IGF)-1 and C-peptide with risk of colorectal cancer.
BACKGROUND
Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor.


METHODS
Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH)D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.


RESULTS
Compared to participants with high 25(OH)D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH)D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH)D was high (OR:1.20 (95% CI: 0.84 to 1.71, p(interaction): additive =0.06, multiplicative =0.25). Similarly, compared to participants with high 25(OH)D and low molar IGF-1/IGFBP-3 ratio and low C-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptide were at elevated risk for colorectal cancer when 25(OH)D was low (OR =1.90, 95% CI: 1.22 to 2.94) but not when 25(OH)D was high (OR=1.15, 95% CI: 0.74 to 1.77, p(interaction): additive=0.004; multiplicative=0.04).


CONCLUSIONS
The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels.
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. kana.wu@channing.harvard.edu
Kana
K
Wu
Diane
D
Feskanich
Charles S
CS
Fuchs
Andrew T
AT
Chan
Walter C
WC
Willett
Bruce W
BW
Hollis
Michael N
MN
Pollak
Edward
E
Giovannucci
D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D002096:C-Peptide; D014807:Vitamin D; D007334:Insulin-Like Growth Factor I; C104450:25-hydroxyvitamin D