BMI and Genetic Risk Linked to Second Cancer Risk in Survivors

A prospective cohort study of 14,309 cancer survivors found that higher genetic predisposition to BMI was associated with a modest increase in obesity-related second primary cancer risk. Obesity was associated with higher risk across genetic-risk groups, with no evidence that the association differed by genetic predisposition.

Cohort included 14,309 cancer survivors.
There were 722 obesity-related second primary cancers.
Obesity was associated with higher risk across genetic-score groups.
No interaction between BMI genetic score and obesity was detected.

Researchers analyzed data from 14,309 cancer survivors in the US Cancer Prevention Study II Nutrition Cohort. Participants had a first nonmetastatic invasive cancer diagnosed between 1992 and 2015, provided a biospecimen, and were followed through 2017. The investigators assessed a polygenic score for BMI and measured BMI in relation to obesity-related second primary cancers (SPCs), using Cox proportional hazards models. Median age at first cancer diagnosis was 72.9 years, and median follow-up was 9.1 years.

During follow-up, 722 participants (5.0%) developed an obesity-related SPC. Compared with the lowest tertile of genetic predisposition to higher BMI, the highest tertile was associated with greater risk (hazard ratio [HR], 1.26; 95% CI, 1.06-1.51). Obesity was associated with increased risk across all genetic-score tertiles, with no evidence of interaction (P=.89). Relative to survivors with low genetic predisposition and BMI below 25, risk was higher among those with obesity and low genetic predisposition (HR, 1.59; 95% CI, 1.21-2.09) and highest among those with obesity and high genetic predisposition (HR, 1.82; 95% CI, 1.38-2.40).

The observational findings suggest that obesity-related SPC risk is not confined to people with high genetic predisposition to BMI. The study does not test whether weight management reduces SPC incidence, and its cohort was older on average; the results do not establish the effects of specific interventions.

In practice

For cancer survivors, this cohort found higher obesity-related second primary cancer risk among people with obesity across all levels of genetic predisposition to BMI; the genetic score did not materially modify the observed association. The findings do not support using this polygenic score to identify who is at risk or to guide a change in clinical management. Because the study was observational and did not test weight-management interventions, it cannot show that weight loss prevents second cancers.

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Source

JAMA Network Open: Body Mass Index, Genetic Predisposition, and Obesity-Related Second Cancer Risk in Cancer Survivors ↗

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