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Insulin-like growth factor-1 and site-specific cancers: A Mendelian randomization study.

Published version
Peer-reviewed

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Authors

Carter, Paul 
Vithayathil, Mathew 
Kar, Siddhartha 

Abstract

Insulin-like growth factor-1 (IGF-1) is involved in several processes relevant to carcinogenesis. We used 416 single-nucleotide polymorphisms robustly associated with serum IGF-1 levels to assess the potential causal associations between this hormone and site-specific cancers through Mendelian randomization. Summary-level genetic association estimates for prostate, breast, ovarian, and lung cancer were obtained from large-scale consortia including individuals of European-descent. Furthermore, we estimated genetic associations with 14 site-specific cancers in European-descent individuals in UK Biobank. Supplementary analyses were conducted for six site-specific cancers using summary-level data from the BioBank Japan Project. Genetically predicted serum IGF-1 levels were associated with colorectal cancer. The odds ratio (OR) per standard deviation increase of IGF-1 levels was 1.11 (95% confidence interval [CI] 1.01-1.22; P = .03) in UK Biobank and 1.22 (95% CI 1.09-1.36; P = 3.9 × 10-4 ) in the BioBank Japan Project. For prostate cancer, the corresponding OR was 1.10 (95% CI 1.01-1.21; P = .04) in UK Biobank, 1.03 (95% CI 0.97-1.09; P = .41) in the prostate cancer consortium, and 1.08 (95% CI 0.95-1.22; P = .24) in the BioBank Japan Project. For breast cancer, the corresponding OR was 0.99 (95% CI 0.92-1.07; P = .85) in UK Biobank and 1.08 (95% CI 1.02-1.13; P = 4.4 × 10-3 ) in the Breast Cancer Association Consortium. There was no statistically significant association between genetically predicted IGF-1 levels and 14 other cancers. This study found some support for a causal association between elevated serum IGF-1 levels and increased risk of colorectal cancer. There was inconclusive or no evidence of a causal association of IGF-1 levels with prostate, breast, and other cancers.

Description

Keywords

Mendelian randomization, cancer, insulin-like growth factor, neoplasm, Asian People, Biomarkers, Tumor, Colorectal Neoplasms, Europe, Female, Humans, Insulin-Like Growth Factor I, Japan, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Up-Regulation, White People

Journal Title

Cancer Med

Conference Name

Journal ISSN

2045-7634
2045-7634

Volume Title

Publisher

Wiley
Sponsorship
Wellcome Trust (204623/Z/16/Z)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
Medical Research Council (MC_UU_00002/7)