Association between CA repeat polymorphism in IGF1 gene promoter and colorectal cancer risk in a native Chinese population

Xiang-Li Chao, Le-Le Wang,  Rui Liu, Yang Li, Xiao-Jie Zhou

Abstract:

Insulin-like growth factor 1 (IGF1) is implicated in normal cell growth. It has been reported that IGF1 has a mitogenic and anti-apoptotic effect on colorectal cancer cells. However, results of studies on the association between cytosine-adenine (CA) repeat polymorphism in IGF1 gene promoter and colorectal cancer (CRC) risk are inconsistent. We aimed to evaluate the association between CA repeat polymorphism and CRC risk, as well as the relationship with the clinicopathological characteristics of CRC and circulating IGF1 level in a native Chinese population. There were 734 participants who were native Chinese in this case-control study, including 367 CRC cases and 367 age- and sex-matched controls. CA repeat polymorphism was genotyped by PCR and fragment analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by unconditional logistic regression analysis. Circulating level of IGF1 in cases was significantly higher than that in controls (p=0.002), particularly in males. Less than 38 CA repeats were associated with decreased CRC risk after adjusting for age and sex (37 versus 38 CA repeats: OR=0.45; 95% CI=0.26–0.78), especially in males. (CA)18/19 genotype showed approximately half reduced CRC risk comparing to (CA)19/19 genotype (OR=0.46; 95% CI=0.25–0.85). There was a significant association between the sum of CA repeats and degree of differentiation of CRC (p=0.044). We observed a trend that circulating level of IGF1 in individuals with CA ≤38 repeats was lower than that in individuals with CA >38 repeats with a borderline statistical significance in overall and males. In conclusion, our findings support the possible role of CA repeat polymorphism in CRC risk.