Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study.
Disruption of the balance of IGF (Insulin like growth factor) pathway constituents has been implicated in the etiology and progression of breast and other cancers. We hypothesized that genetic polymorphisms in IGF system members may be associated with breast cancer survival and evaluated this hypothesis in a cohort of 1,455 women diagnosed with breast cancer between 1996 and 1998 in Shanghai, China. Nineteen functional or potentially functional polymorphisms were evaluated in the IGF-1, IGF-1R, IGFALS, and IGFBP3 genes. Disease recurrence and vital status were obtained with a median follow-up time of 7.1 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Overall, no significant association was noted between any of the 19 polymorphisms and survival. However, subgroup analyses demonstrated apparent interactions between menopausal status and survival for several (Single nucleotide polymorphism) SNPs in the IGF-1R and IGFBP3 genes. Carriers of the A/G or G/G genotypes (rs951715) in the IGF-1R gene had an increased risk of death among post-menopausal women (HR = 1.7, 95% CI = 1.1-2.7). Significant associations with breast cancer survival in pre-menopausal women were found for two IGFBP3 polymorphisms (rs2854744 and rs3110697), with an additional polymorphism (rs6413441) reaching borderline significance (P = 0.05). Hazard ratios for overall survival among pre-menopausal women were 1.5 (95% CI = 1.1-2.0) for the C/T-T/T genotypes (rs3110697), 1.4 (95% CI = 1.0-1.9) for the A/C-C/C genotypes (rs2854744), and 1.4 (95% CI = 1.0-1.9) for the N/A-A/A genotypes (rs6413441). Taken together, these data suggest that polymorphisms in the IGF-1R and IGFBP3 genes may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status.
Deming
Sandra L
SL
Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Ren
Zefang
Z
Wen
Wanqing
W
Shu
Xiao Ou
XO
Cai
Qiuyin
Q
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D016896:Treatment Outcome
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1