Journal
CANCER MEDICINE
Volume 9, Issue 18, Pages 6836-6842Publisher
WILEY
DOI: 10.1002/cam4.3345
Keywords
cancer; insulin-like growth factor; Mendelian randomization; neoplasm
Categories
Funding
- Swedish Research Council for Health, Working Life and Welfare
- Swedish Research Council
- Swedish HeartLung Foundation
- Integrative Cancer Epidemiology Programme [C18281/A19169]
- Homerton College
- National Institute for Health Research
- Wellcome Trust
- Royal Society [204623/Z/16/Z]
- Cambridge University Hospitals NHS Foundation Trust
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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 x 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 x 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.
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