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Cited by 1,707Cancer Risks and FactorsObesity, Physical Activity, DietGlobal Cancer Incidence and Screening

Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults

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Bhaskaran, Krishnan, Douglas, Ian, Forbes, Harriet, dos-Santos-Silva, Isabel, Leon, David A, Smeeth, Liam·2014·The Lancet
DOI 10.1016/s0140-6736(14)60892-8PMC PMC4151483
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Abstract

BACKGROUND: High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS: With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS: 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION: BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING: National Institute for Health Research, Wellcome Trust, and Medical Research Council.

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  • Obesity is a recognized risk factor for multiple malignancies, including endometrial, postmenopausal breast, colorectal, pancreatic, esophageal adenocarcinoma, and hepatocellular carcinoma.

    “Obesity is a recognized risk factor for multiple malignancies, including endometrial, postmenopausal breast, colorectal, pancreatic, esophageal adenocarcinoma, and hepatocellular carcinoma.”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [143]

    The Findings and Results report positive BMI associations with uterine, colon, liver, and postmenopausal breast cancers. But the Discussion says evidence for pancreatic cancer was only weak and notes no strong evidence for rectal cancer, limiting the colorectal claim. It also says the study could not distinguish oesophageal adenocarcinoma from other oesophageal cancers; it reports liver cancer without identifying hepatocellular carcinoma specifically. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • Large-scale epidemiologic cohorts and Mendelian randomization studies have established a dose-dependent association between adiposity and cancer incidence and mortality.

    “Large-scale epidemiologic cohorts and Mendelian randomization studies have established a dose-dependent association between adiposity and cancer incidence and mortality [143].”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [143]

    The Results report associations between BMI and incidence of 17 of 22 cancers, including roughly linear increases in risk for several cancer sites. The study is a large epidemiologic cohort, but it does not report a Mendelian randomization analysis or establish an association with cancer mortality. Its Discussion also notes that the direction and size of associations vary by cancer type, so a general dose-dependent increase is too broad. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Authors
Bhaskaran, K., Douglas, I., Forbes, H., dos-Santos-Silva, I., Leon, D. A., & Smeeth, L.
Affiliations
London School of Hygiene & Tropical Medicine (GB)
Corresponding author
Bhaskaran, Krishnan
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2014-08
Volume
384
Issue
9945
Pages
755-765
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(14)60892-8
PMC
PMC4151483
OpenAlex
W2155226662
Cited by
1,707
References
7
Citations by year
2026: 67 · 2025: 128 · 2024: 153 · 2023: 170 · 2022: 180 · 2021: 160 · 2020: 165 · 2019: 144 · 2018: 137 · 2017: 164 · 2016: 121 · 2015: 92 · 2014: 25
FWCI
64.74
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Bristol Research (University of Bristol) (submittedVersion)
Funders
  • Wellcome Trust (098504)
  • National Institute for Health and Care Research (NIHR/CS/010/014, NF-SI-0510-10090, PDF-2011-04-007)
  • Medical Research Council (MR/K006584/1)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
  • Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
Keywords
body mass index, obesity, cancer risk, site-specific cancer, uterine cancer, gallbladder cancer, kidney cancer, cervical cancer, thyroid cancer, leukemia, liver cancer, colon cancer, ovarian cancer, postmenopausal breast cancer, prostate cancer, premenopausal breast cancer, effect modification, sex differences, menopausal status, smoking, population attributable fraction
MeSH terms
Adult, Female, United Kingdom, Humans, Male, Middle Aged, Neoplasms, Risk, Cohort Studies, Body Mass Index, Proportional Hazards Models

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