Cohort studyindependent cross-checkabstract checked I-DRY-110 standard review
Higher IGF-1 linked to prostate cancer, supported by genetics
Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank.
Overview
Watts EL et al.. Int J Cancer 2021 · PMID 33252839 · DOI 10.1002/ijc.33416
Per 5 nmol/L IGF-I: 9% higher diagnosis risk; genetic analysis OR 1.34.
Does the study support the specific claim? Partly · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test hormones and prostate cancer.
- How was the study done?
Cohort plus MR.
- How many people, animals or samples were studied?
About 200,000 men.
- What was actually found?
IGF-I and free testosterone linked to higher risk.
- How large was the observed effect?
HR 1.09 per 5 nmol/L.
- What do the results mean in everyday life?
IGF-1 is a plausible prostate cancer factor.
- What are the study's limitations?
Does not test milk.
- What does it say about Elawady's specific claim?
Supports one link of the mechanism.
- Do the results apply to Germany and Europe?
UK data.
- What can explicitly not be concluded from this study?
Cannot show that milk-induced IGF-1 causes cancer.
Scientific in-depth review
1. Full reference
- Authors
- Watts EL et al.
- Journal
- Int J Cancer
- Year
- 2021
- Identifier
- PMID 33252839 DOI 10.1002/ijc.33416
- Verification
- verified – PubMed efetch 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Cancer Research UK, MRC, Wellcome, NCI and others (record).
2. Research question
Are circulating IGF-I and testosterone associated with prostate cancer incidence and mortality?
3. Study design and population
- Study design
- Cohort study – Prospective cohort (UK Biobank) with regression-dilution correction plus two-sample Mendelian randomisation (PRACTICAL)
- Population
Men in UK Biobank; PRACTICAL consortium
- Country
UK/international
- Period
mean 6.9 y
- Sample size
199,698 men; 5402 cases; 295 deaths; MR 79,148 cases/61,106 controls
- Inclusion and exclusion criteria
UK Biobank men with hormone measurements
4. Methods and endpoints
- Exposure / intervention
Serum IGF-I, testosterone, SHBG
- Comparator
Per increment
- Endpoints
Prostate cancer diagnosis and death
- Statistical methods
Cox regression; cis- and all-SNP MR
5. Actual results
- Results
IGF-I HR per 5 nmol/L 1.09 (1.05-1.12) for diagnosis and 1.15 (1.02-1.29) for mortality; cis-MR OR per 5 nmol/L 1.34 (1.07-1.68). Free testosterone HR per 50 pmol/L 1.10 (1.05-1.15).
- Absolute risks
not reported
- Authors' conclusion
Findings implicate IGF-I and free testosterone in prostate cancer development and/or progression.
6. Strengths
- Very large
- Repeat measures
- MR support
7. Weaknesses
- Does not examine diet
- MR instrument assumptions
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Prospective, standardised assays; MR adds causal support.
9. Assessment of the statistical interpretation
Moderate per-unit effect; diagnosis HR CI slightly asymmetric due to rounding.
10. Relevance to the specific claim
Strengthens the second link of the claimed mechanism (IGF-I -> prostate cancer), including genetic evidence.
11. Independent contrary findings
The first link (dairy -> IGF-I rise large enough to matter) and mediation remain unproven (A-DRY-14; I-DRY-109).
12. Transferability to Germany and Europe
Biological.
13. Overall methodological judgement
Good evidence that IGF-I is a causal risk factor for prostate cancer; says nothing directly about milk.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | high |
| Directness | indirect |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
How much diet-induced IGF-I changes matter.