A polygenic risk score is associated with risk of bladder cancer and earlier age of diagnosis, independent of lifestyle factors.

BACKGROUND

Genetic risk factors are not currently incorporated into the clinical evaluation of patients at risk for bladder cancer (BCa). The objective of this study is to assess the independent and joint effects of genetic and lifestyle factors on the risk of developing BCa and age at diagnosis.

METHODS

This is a population-based cohort study of the UK Biobank, consisting of 3,373 BCa cases and 481,275 controls. A polygenic risk score (PGS) was calculated and the effect of lifestyle and genetic factors on BCa risk was estimated using hazard ratio (HR).

RESULTS

The PGS was a significant and independent predictor of the risk of BCa diagnosis. Compared to never-smokers with BMI <30 and a PGS in the lowest decile, current smoking was associated with a HR of 4.47 (95% CI 3.35-5.98) and a PGS in the highest decile was associated with a HR of 4.57 (95% CI 3.44-6.09). Risk was highest for current smokers with BMI ≥30 and a PGS in the highest decile (HR 8.14, 95% CI 4.95-13.36). Most study subjects (∼95%) were of European ancestry.

CONCLUSION

The PGS was an independent and significant predictor of the risk of BCa and earlier age at diagnosis. The effect size of PGS in the highest decile was similar to that of smoking. Joint effects were observed with smoking status and BMI. These data provide support for incorporating measures of genetic risk factors in efforts to improve early detection of BCa.