Participants with cancer (except non-melanoma skin cancer) at baseline (51,234), proxy respondents (15,760), those who died or who were diagnosed with cancer on the first day of follow-up (13), or failed to provide information about cigarette use (19,329) or cigar and pipe use (12,537) were excluded, resulting in an analytic cohort of 281,394 men and 186,134 women. Men and women entered the study at similar ages, but men had more formal education, drank more alcohol, ate less fruit and vegetables, and were more likely to have ever smoked cigarettes, pipes, or cigars and to have smoked more than 40 cigarettes per day than women. But, a higher proportion of women than men were current smokers. The median age of smoking initiation was 17 in the subset of the cohort (118,557 men and 72,030 women) who returned a follow-up questionnaire in September 2004 ().
Characteristics of the NIH-AARP cohort by sex.
Over the course of 4,518,938 years of follow-up, 3,896 men and 627 women were newly diagnosed with bladder cancer. Overall incidence rates were 144.0/100,000 person-years (95%CI: 139.4–148.5) in men and 34.5/100,000 person-years (95%CI: 31.8–37.3) in women. Cigarette smoking was a strong risk factor for bladder cancer in both sexes (). Relative to never smokers (men: 69.8/100,000 person-years; women: 16.1/100,000 person-years), former and current smokers had elevated risk of bladder cancer in both men (former, 154.6/100,000 person-years, HR: 2.14 (95%CI: 1.92–2.37), NNH: 1,179; current, 276.4/100,000 person-years, HR: 3.89 (95%CI: 3.46–4.37), NNH: 484) and women (former, 40.7/100,000 person-years, HR: 2.52 (95%CI: 2.05–3.10), NNH: 4,065; current, 73.6/100,000 person-years, HR: 4.65 (95%CI: 3.73–5.79), NNH: 1,739). The combined risk estimates including both sexes were 2.22 (95%CI: 2.03–2.44) for former smokers (119.8/100,000 person-years; NNH: 1,250: 95%CI: 1,171–1,343) and 4.06 (95%CI: 3.66–4.50) for current smokers (177.3/100,000 person-years; NNH: 727, relative to never smokers (39.8/100,000 person-years).
Incidence rates and hazard ratios (95% CIs) for cigarette smoking and bladder cancer by sex
As in previous studies, smoking cessation was associated with reduced bladder cancer risk in both sexes. Participants who quit ≥ 10 years before baseline had lower incidence rates of bladder cancer than those who quit 1–5 or 5–<10 years before baseline. Nevertheless, relative to never smokers, risks remained elevated for men and women who quit even ≥10 years before baseline. Pipe and cigar use was also associated with risk in men (HR: 1.29, 95%CI: 1.07–1.56; 92.5/100,000 person-years vs. 69.8/100,000 person-years; NNH: 4,405. Too few women in the cohort smoked pipes or cigars to be analyzed.
Overall, men had 3.71 (95%CI: 3.39–4.06; 144.0/100,000 person-years vs. 34.5/100,000 person-years) times the risk of women for bladder cancer (). Among stratum of cigarette smoking, risks for men relative to women ranged from 1.99 to 6.62. Elevated rates persisted in never-smokers where men (69.8/100,000 person-years) had 4.07 (95%CI: 3.34–4.97) times the bladder cancer risk of never-smoking women (16.1/100,000 person-years).
Incidence rates and hazard ratios (95% CIs) for joint categories of smoking dose and cessation
The PAR for ever smoking in the NIH-AARP study was similar in men (0.50, 95%CI: 0.45–0.54) and women (0.52, 95%CI: 0.45–0.59).
Next, we performed a systematic review and meta-analysis of previously published US prospective cohort studies of current cigarette smoking and incident bladder cancer (Supplementary Figure 1
). We identified data from the seven cohorts (). In these cohorts initiated between 1963 and 1987, the summary risk estimate was 2.94 (95%CI: 2.45–3.54) with an I2
of 0.0% and the Cochran Q test p-value for between study heterogeneity was 0.554. We observed no evidence for publication bias by either Egger's weighted regression (p-value =0.315) or Begg and Mazumdar's rank correlation method (p-value =0.293).
Relative risks of incident bladder cancer for current smokers relative to never smokers in previously published studies from United States prospective cohorts*
Addition of risk estimates from the NIH-AARP study to the meta-analysis raised the summary risk estimate to 3.75 (3.43–4.10) and increased the I2 to 48.7%, such that the Cochran Q test p-value for between study heterogeneity became statistically significant (p=0.049).