Table 4.

Differences in 30-year absolute risk of developing bladder cancer in U.S. white males aged 50 years according to smoking status and quartiles of a polygenic risk score

CasesaControlsaCurrent vs. NeverCurrent vs. FormerPadd
N/F/CN/F/CRDb (95% CI)PaddcRDb (95%CI)Paddd1 dfe2 dff
Smoking status245/849/264464/704/1564.9% (3.7%–6.9%)N/A3.3% (2.0%–5.2%)N/AN/AN/A
Smoking status by quartiles of a polygenic risk scoreg
Score 0 (low risk)37/98/3498/174/472.0% (0.8%–3.8%)Ref.1.5% (0.3%–3.2%)Ref.Ref.Ref.
Score 161/197/66117/185/355.3% (2.8%–8.6%)0.0203.8% (1.4%–7.3%)0.0841.9 × 10−36.4 × 10−3
Score 272/249/65129/174/384.9% (2.5%–8.5%)0.0292.8% (0.4%–6.4%)0.4413.9 × 10−42.0 × 10−3
Score 3 (high risk)84/305/99120/171/368.2% (4.7%–13.1%)1.1 × 10−45.4% (2.0%–10.4%)0.0631.2 × 10−73.3 × 10−7
  • aNumber of never/former/current (N/F/C) cases and controls

  • bDifferences in absolute risks (RDs) are calculated on the basis of case frequencies and ORs (adjusted for study, age, and gender) for smoking status and PRS in white males in the U.S. studies with complete smoking (excluding occasional smokers) and PRS data (1,324 cases and 1,367 controls from PLCO, NEBCS (ME, VT), CPSII), SEER17 urinary bladder cancer age-specific incidence rates from 2005–2007 in white males, mortality rates from causes other than urinary bladder cancer from U.S. Mortality 2000–2007, with Kaposi sarcoma and mesothelioma in white males.

  • cP values from 1 df additive interaction tests comparing RDs for current versus never smokers in different polygenic risk categories.

  • dP values from 1 df additive interaction tests comparing RDs for current and former smokers in different polygenic risk categories.

  • eP values from 1df additive interaction tests comparing RDs for ever and never smokers in different polygenic risk categories. The ever smoking category includes former and current smokers, plus additional subjects from NEBCS classified as occasional smokers.

  • fP from 2 df additive interaction tests comparing RDs for current, former, and never smokers in different polygenic risk categories.

  • gPolygenic risk score calculated as quartiles of a linear predictor including the 12 SNPs in Table 2. Median (range) number of risk alleles for each PRS category in the control population is: 10 (5–14) for score 0; 12 (9–17) for score 1; 13 (11–16) for score 2; and 15 (13–20) for score 3. The maximum number of risk alleles is 20 because 2 SNPs (rs11892031 and rs17863783) are considered as dichotomous variables.