A case-control study of smoking and bladder cancer risk: emergent patterns over time

Abstract

Background: Cigarette smoking is a well-established risk factor for bladder cancer. The effects of smoking duration, intensity (cigarettes per day), and total exposure (pack-years); smoking cessation; exposure to environmental tobacco smoke; and changes in the composition of tobacco and cigarette design over time on risk of bladder cancer are unclear.

Methods: We examined bladder cancer risk in relation to smoking practices based on interview data from a large, population-based case-control study conducted in Maine, New Hampshire, and Vermont from 2001 to 2004 (N = 1170 urothelial carcinoma case patients and 1413 control subjects). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. To examine changes in smoking-induced bladder cancer risk over time, we compared odds ratios from New Hampshire residents in this study (305 case patients and 335 control subjects) with those from two case-control studies conducted in New Hampshire in 1994-1998 and in 1998-2001 (843 case patients and 1183 control subjects).

Results: Regular and current cigarette smokers had higher risks of bladder cancer than never-smokers (for regular smokers, OR = 3.0, 95% CI = 2.4 to 3.6; for current smokers, OR = 5.2, 95% CI = 4.0 to 6.6). In New Hampshire, there was a statistically significant increasing trend in smoking-related bladder cancer risk over three consecutive periods (1994-1998, 1998-2001, and 2002-2004) among former smokers (OR = 1.4, 95% CI = 1.0 to 2.0; OR = 2.0, 95% CI = 1.4 to 2.9; and OR = 2.6, 95% CI = 1.7 to 4.0, respectively) and current smokers (OR = 2.9, 95% CI = 2.0 to 4.2; OR = 4.2, 95% CI = 2.8 to 6.3; OR = 5.5, 95% CI = 3.5 to 8.9, respectively) (P for homogeneity of trends over time periods = .04). We also observed that within categories of intensity, odds ratios increased approximately linearly with increasing pack-years smoked, but the slope of the increasing trend declined with increasing intensity.

Conclusions: Smoking-related risks of bladder cancer appear to have increased in New Hampshire since the mid-1990s. Based on our modeling of pack-years and intensity, smoking fewer cigarettes over a long time appears more harmful than smoking more cigarettes over a shorter time, for equal total pack-years of cigarettes smoked.

Figure 1

Trend in smoking-induced bladder cancer in New Hampshire from 1994 to 2004. Odds ratios (ORs) and 95% confidence intervals for bladder cancer are shown for former and current smokers relative to never-smokers during three consecutive time intervals: from July 1, 1994, to June 30, 1998 (372 case patients and 456 control subjects) (white bars); from July 1, 1998, to December 31, 2001 (324 case patients and 328 control subjects) (light gray bars); and from January 1, 2002, to December 31, 2004 (253 case patients and 199 control subjects) (dark gray bars).

Figure 2

Odds ratios (ORs) and 95% confidence intervals for bladder cancer among smokers, relative to never-smokers, by categories of total pack-years of exposure and cigarettes smoked per day (cigs/d), and fitted linear models for the odds ratios by pack-years (square symbols).

Figure 3

Estimates of the excess odds ratio (EOR) per pack-year for categories of intensity (<5, 5–9, 10–14, 15–19, 20–24, 25–29, 30–39, ≥40 cigarettes per day). The EOR per pack-year and 95% confidence intervals were plotted at the mean numbers of cigarettes per day within each category (square symbols). The three models shown are fitted to all data (solid line), to all data excluding smokers who consumed less than 10 cigarette per day (dashed line), and to all data excluding smokers who consumed less than 10 cigarettes per day with intensity effects fixed at φ₁ = 2.72 and φ₂ = −0.479 (Equation 1 in Appendix 1) determined from a previous analysis of multiple smoking-related cancer studies (dotted line) (21).