Disturbing Link Between Smoking and Bladder Cancer

Bladder Cancer Study Unveils New Potential Targeted Therapies
Bladder Cancer Study Unveils New Potential Targeted Therapies
New research confirms smoking significantly increases risk for developing bladder cancer and also reveals a gene that may protect against the disease.

Cigarette smoke contains known bladder carcinogens—such as ß-naphthylamine, polycyclic aromatic hydrocarbons, and other aromatic amines—that are excreted renally, allowing a direct effect on bladder and other urinary tract tissues.1

Across populations, rates of bladder cancer and associated mortality are higher in both current and former smokers than in never-smokers; in addition, it is well recognized that cigarette smoking is the major risk factor for urothelial bladder cancer.1,2

Connecting the Dots Between Smoking and Bladder Cancer

Two recent studies give further insight into the association between smoking and bladder cancer. One of these studies suggests that smokers are more likely to have advanced disease at diagnosis, while the other finds that a polymorphism in the x-ray repair cross-complementing group 1 (XRCC1) gene may play a role in protecting smokers from developing the disease.3,4

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More than 72,000 Americans will be diagnosed with bladder cancer this year. The disease occurs more often and results in more deaths among men than women, a difference partially attributed to higher rates of smoking among men.

However, past trends show that as the number male smokers decreases and the number of female smokers increases, bladder cancer rates between the sexes have followed a similar pattern. Today, men and women smoke at similar rates in the United States, and it is no coincidence that a 2011 NIH/AARP study concluded that smoking is implicated in about half of all bladder cancer cases in both men and women.1,6

A meta-analysis of epidemiologic studies published in 2000 estimated that current smokers had a three-fold higher risk for developing bladder cancer compared with never-smokers.7 Since then, a number of studies in the United States have examined the magnitude of smoking-related risk for bladder cancer. In general, these studies concur that the risk for current—and some former—smokers is anywhere from 2.5 to more than 5 times higher than that of never-smokers (Table 1).6,8-10

Table 1: Risk for Bladder Cancer Associated With Current Cigarette Smoking*

Study Study design Risk (95% CI)
Prospective cohort, nationwide
Men: n=281,394
Women: n=186,134
Men: HR=3.89 (3.46-4.37)
Women: HR=4.65 (3.73-5.79)
Baris 200910 Case-control study, New England
N=1,170 cases
N=1,413 controls
OR=5.2 (4.0-6.6)
Alberg 20078 Two-part prospective cohort, Maryland N=45,749 (in 1963)
N=48,172 (in 1975)
1963: RR=2.7 (1.6-4.7)
1975: RR=2.6 (1.7-3.9)
Iowa Women’s Study9 Prospective cohort, women, Iowa
RR=3.58 (1.86-6.88)
*Versus never smokers as reference.
Abbreviations: HR, hazard ratio; OR, odds ratio; RR, relative risk.

An interesting trend has also emerged, suggesting that bladder cancer risk from smoking has increased from the early 1990s through 2004, possibly due to the higher concentrations of carcinogens in cigarette smoke since the 1990s.2,10 

Does Smoking Duration and Intensity Affect Risk?

Three in four bladder cancers are non–muscle invasive. Ninety percent of bladder cancers are transitional cell carcinomas; the remainder is comprised of squamous cell carcinoma or adenocarcinomas.11 

Smoking increases risk for all subtypes of bladder cancer, but the risk overall is influenced by duration and intensity of smoking;  as a result, individuals with the longest smoking history or greatest intensity are at significantly higher risk for developing high-grade noninvasive and invasive disease than for developing low-grade noninvasive disease.9,10,12

This article originally appeared on Cancer Therapy Advisor