| Title: | Insulin-like growth factor-1 and site-specific cancers: A Mendelian randomization study |
| Journal: | Cancer Medicine |
| Published: | 27 Jul 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32717139/ |
| DOI: | https://doi.org/10.1002/cam4.3345 |
| URL: | https://research-information.bris.ac.uk/files/247407554/untitled.pdf |
| Citations: | 40 (11 in last 2 years) as of 8 Aug 2024 |
Publication 5244
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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.</p>
15 Keywords
- 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
6 Authors
- Susanna C. Larsson
- Paul Carter
- Mathew Vithayathil
- Siddhartha Kar
- Amy M. Mason
- Stephen Burgess
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