Interactions between Plasma Levels of 25-Hydroxyvitamin D, Insulin-Like Growth Factor (IGF)-1 and C-Peptide with Risk of Colorectal Cancer

Kana Wu,Walter C Willett,Edward Giovannucci,Bruce W Hollis,Charles S Fuchs,Michael N Pollak,Diane Feskanich,Andrew T Chan,Libing Song

doi:10.1371/journal.pone.0028520

Abstract

BackgroundVitamin 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.MethodsCombining 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.ResultsCompared 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).ConclusionThe 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.

Highlights

Both vitamin D status and levels of insulin-like growth factor (IGF)-1 has been implicated in colorectal carcinogenesis [1,2,3]
Cases had significantly higher mean plasma IGF-1 levels and molar IGF-1/IGFBP-3 ratio as well as lower plasma 25(OH)D levels compared to controls (Table 1)
Consistent with results reported in our previous publications on colorectal or colon cancer from our cohorts [6,8,21], in multivariable analyses higher IGF-1 and C-peptide levels and IGF-1/IGFBP-3 molar ratio were significantly associated with higher risk of colorectal and colon cancer and higher plasma 25(OH)D levels were significantly associated with lower risk of colorectal and colon cancer (Table 2)

Summary

Introduction

Both vitamin D status and levels of insulin-like growth factor (IGF)-1 has been implicated in colorectal carcinogenesis [1,2,3]. Several but not all prospective studies have found evidence for a positive association between higher levels of IGF-1 or the molar ratio of IGF-1 and its primary binding protein, IGF-binding protein 3 [11] (IGF-1/ IGFBP-3 ratio) and colorectal and/or colon cancers [12,13,14,15,16,17,18,19]. High levels of insulin (or C-peptide, a marker for insulin production [20]) may increase risk of colorectal cancer [13,16,21,22,23]. Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. In contrast to vitamin D IGF-1 is not an modifiable risk factor

Methods

Results

Conclusion