PublishedSeptember 24, 2026
JournalJAMA Oncology

Modifiable Risk Factors Account for an Estimated 84% of the Male–Female Cancer Gap in China but 26% in the UK

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Article Summary
  • A multicohort analysis of 589,766 adults aged 40 to 74 years without prior cancer, drawn from the Shanghai Men’s Health Study, the Shanghai Women’s Health Study and UK Biobank, estimated how much of the higher cancer incidence in males is attributable to 11 lifestyle factors and health conditions.
  • The 11 factors jointly accounted for 84.44% of the male–female incidence rate difference in China (joint attributable rate difference [ARD] 182.52 cases per 100,000 person-years; 95% CI, 162.46–202.26) but 26.21% in the UK (joint ARD 52.31; 95% CI, 35.63–70.22). In China, smoking alone accounted for 51.75% of the gap.
  • These are quantitative attributions under model assumptions, not definitive causal partitions. The study is observational, relies on baseline self-reported exposures, and could not measure occupational, environmental or biological contributors.

Why This Study Matters

Cancer risk is higher in males than females globally. Whether this sex disparity reflects a biological inevitability or is potentially modifiable by lifestyle behaviors and health conditions across diverse populations remained unclear. This study set out to determine the contribution of lifestyle factors and health conditions to sex disparities in cancer incidence across populations.

1
In 589,766 adults, 70,300 non–sex-specific cancers were documented.
2
China (134,742 participants): joint attributable rate difference (ARD) of 182.52 (95% CI, 162.46–202.26) cases per 100,000 person-years, accounting for 84.44% of the male–female incidence rate difference.
3
UK (455,024 participants): joint ARD of 52.31 (95% CI, 35.63–70.22), accounting for 26.21%.
4
Smoking alone: 51.75% of the gap in China (ARD 111.87 [95% CI, 95.38–128.00]).

Study Design

Individual-level analysis of 3 population-based prospective cohorts of adults aged 40 to 74 years at baseline with no prior cancer. Baseline data were collected from 1997 to 2010, with follow-up through 2021. Eleven risk factors were assessed: smoking, heavy alcohol drinking, physical inactivity, low intakes of vegetable and fruit, high intakes of red meat and processed meat, cholelithiasis, chronic liver diseases, diabetes and obesity. The main outcome was incidence of 34 non–sex-specific cancer end points. Sex-specific population attributable fractions (PAFs) were converted to ARDs (ASIR_male × PAF_male − ASIR_female × PAF_female) and attributable proportions (AP = ARD / [ASIR_male − ASIR_female]). Data were analyzed from September 2025 to June 2026.

The study comprised 589,766 participants, 70,300 incident cancers, 3 prospective cohorts, 11 risk factors and 34 cancer end points. Number of study sites and randomization: not applicable / not specified in source (observational cohorts).

Patient Population

Mean (SD) age was 56.1 (8.5) years; 315,813 (53.5%) were female. The Chinese population comprised 134,742 participants (54.4% female; 45.6% male); the UK Biobank contributed 455,024 participants (53.3% female; 46.7% male). Ever-smoking was reported by 42,765 (69.6%) Chinese males versus 2,042 (2.8%) Chinese females, and by 107,036 (50.7%) UK males versus 95,724 (39.7%) UK females.

Primary Outcome Results

The overall male-to-female incidence rate ratio was 1.66 (95% CI, 1.60–1.72) in China and 1.49 (95% CI, 1.46–1.51) in the UK. Absolute differences in age-standardized incidence rates were 216.15 (95% CI, 197.37–234.93) and 199.62 (95% CI, 184.92–214.32) cases per 100,000 person-years, respectively. The 11 factors jointly accounted for 84.44% of the sex gap in China but 26.21% in the UK. Single-factor and joint estimates are not additive.

Site-Level Joint Contributions (Cancer-Site Analyses)

Cancer siteChina joint ARD (95% CI)China APUK joint ARD (95% CI)UK AP
Non-sex-specific cancers combined182.52 (162.46–202.26)84.44%52.31 (35.63–70.22)26.21%
Lung82.56 (73.92–90.44)137.82%10.37 (7.36–13.33)128.43%
Esophagus10.35 (7.42–13.72)83.36%8.02 (6.39–9.73)68.72%
Stomach17.30 (10.29–23.82)48.61%3.38 (1.88–4.80)49.50%
Colon11.56 (4.33–18.67)101.70%6.62 (2.55–10.77)86.35%
Rectum14.60 (8.79–20.29)100.76%6.11 (2.93–9.08)45.01%
Liver26.10 (21.82–30.82)78.55%4.97 (3.90–6.06)90.99%
Pancreas3.75 (−0.20–7.17)47.77%1.94 (0.24–3.67)48.14%
Bladder6.55 (2.96–10.33)38.66%6.99 (5.50–8.49)48.53%

ARD in cases per 100,000 person-years. AP values are reproduced as printed in the source figure. Subgroup analyses beyond these site-level estimates (e.g., by age or ethnicity) are not reported numerically in the source: not specified in source.

Leading Individual Contributors

FactorChina ARD (95% CI)China APUK ARD (95% CI)UK AP
Cigarette smoking111.87 (95.38–128.00)51.75%12.49 (1.82–24.39)6.26%
Heavy alcohol drinking32.64 (24.61–40.43)15.10%Not specified in sourceNot specified in source
Chronic liver diseases21.72 (17.68–26.24)10.05%Not specified in sourceNot specified in source
Low fruit intake21.42 (11.53–31.42)9.91%Not specified in sourceNot specified in source
ObesityNot specified in sourceNot specified in source15.34 (6.06–24.08)7.68%
DiabetesNot specified in sourceNot specified in source7.00 (3.39–10.56)3.51%

In China, metabolic factors including obesity and diabetes contributed minimally to the gap for non–sex-specific cancers combined; in the UK, contributors were dominated by metabolic rather than behavioral exposures.

Safety Profile

Not applicable — this is an observational cohort study with no therapeutic intervention, and no adverse-event data were reported.

Interpretation and Broader Context

Reducing cancer sex disparities may require prevention strategies tailored to population contexts.

The authors write that in China, targeting tobacco and alcohol control among males could be a potential priority; in the UK the measured factors explained only a modest proportion, underscoring the need to investigate unmeasured occupational and environmental exposures and intrinsic biological determinants. Sensitivity analyses (10-year PAFs, multiple imputation for physical activity, Fine-Gray competing-risk models) were reported as concordant with the primary analysis. The ARD estimates are quantitative attributions under model assumptions and do not represent definitive causal partitions.

Limitations

Limitations noted by the authors: observational design with residual confounding and reverse causation; sex structurally confounded with cohort and calendar time in the Chinese analysis; baseline-only, self-reported exposures; no data on occupational exposures, air pollution or infectious agents; participants aged 40–74 at baseline; urban Chinese and predominantly White European UK Biobank samples.

Primary source: DOI 10.1001/jamaoncol.2026.3747 · PubMed 42783354 · PMC13613232

References

  1. Li Z-Y, Tan Y-T, Shen Q-M, et al. Disparities in Cancer Incidence by Sex and Associated Lifestyle Factors and Health Conditions. JAMA Oncology. Published online September 24, 2026. DOI: 10.1001/jamaoncol.2026.3747. PMID: 42783354. PMCID: PMC13613232.
  2. Funding: National Natural Science Foundation of China (82504486), Shanghai Municipal Bureau of Disease Control and Prevention (2025GKQ04), National Key Project of Research and Development Program of China (2021YFC2500404), and US NIH (subcontracts of UM1 CA173640, CA182910). The funder had no role in the study.