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Does childhood body size itself raise colorectal cancer risk?

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MR of UK Biobank and 125,478 CRC participants suggests early-life larger body size raises CRC odds only until adult BMI is accounted for.

Source

Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study

Papadimitriou N, Bull CJ, Jenab M, et al. · BMC medicine · 2023

doi.org/10.1186/s12916-022-02702-9Read the full paper ↗28 citationscc by

Study at a glance

Design
Mendelian randomisation — Univariable and multivariable MR of early-life body size vs adult BMI with colorectal cancer GWAS
N
N=125478 · CRC GWAS meta-analysis of 125,478 participants; body-size GWAS from 453,169 UK Biobank participants
Population
UK Biobank body-size GWAS plus three colorectal-cancer consortia (summary statistics)
Outcome
Odds of colorectal, colon, distal colon, and proximal colon cancer for genetically predicted early-life vs adult body size

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Used univariable and multivariable Mendelian randomization: genetically predicted self-perceived body size at age 10 and adult BMI (mean age 56.5) from 453,169 UK Biobank participants, against CRC GWAS meta-analysis of 125,478 people.

What they found

Early-life body size OR for CRC 1.12 (0.98–1.27), colon 1.16, distal colon 1.25 (1.04–1.51). After multivariable MR for adult size, early-life effects attenuated (CRC OR 0.97). Adult body size still raised CRC (OR 1.27), colon (1.32), and proximal colon (1.57) odds.

The limits

What it doesn't show

MR depends on instrument assumptions and self-perceived childhood size; it does not map a clinical weight-loss trial in children vs adults.

Key terms

Mendelian randomization
Uses genetic variants as instruments to probe causal effects.
Multivariable MR
Estimates independent effects of correlated exposures (here early vs adult size).
Early-life body size
Self-perceived thinner/plumper/average at age 10.
UK Biobank
Large UK cohort supplying the body-size GWAS.
Colorectal cancer
Cancer of colon or rectum; analysed overall and by subsite.

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CRC GWAS sample was about:

Common questions

CRC GWAS N?

125,478 participants from three consortia.

Univariable early-life CRC OR?

1.12 (95% CI 0.98–1.27) per category.

After adjusting for adult size?

Early-life CRC OR attenuated to 0.97.

Authors’ interpretation?

Childhood association likely reflects larger size kept into adulthood.

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