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Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study

  • Epidemiology
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Abstract

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.

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Acknowledgments

The authors wish to express their gratitude to Drs. Qi Dai and Fan Jin for the contributions in coordinating data and specimen collection in Shanghai, Bethanie Hull for her technical assistance in the preparation of this manuscript, and all of the study participants and research staff of the Shanghai Breast Cancer Study.

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  1. Zefang Ren

    Present address: Guangzhou Center for Disease Prevention and Control, Guangzhou, China

Authors and Affiliations

  1. Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Sandra L. Deming, Zefang Ren, Wanqing Wen, Xiao Ou Shu, Qiuyin Cai & Wei Zheng

  2. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

    Yu-Tang Gao

  3. Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, S-1121A MCN, 1161 21st Ave S., Nashville, TN, 37232, USA

    Wei Zheng

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  1. Sandra L. Deming
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  2. Zefang Ren
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Correspondence to Wei Zheng.

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Deming, S.L., Ren, Z., Wen, W. et al. Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study. Breast Cancer Res Treat 104, 309–319 (2007). https://doi.org/10.1007/s10549-006-9420-8

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  • DOI: https://doi.org/10.1007/s10549-006-9420-8

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