Women are at higher risk for high-grade noninvasive and invasive disease compared with men with similar smoking histories and intensity.12 Smoking cessation reduces, but appears not to eliminate, the excess risk associated with tobacco use.

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While the risk for former smokers becomes substantially decreased over time, it appears not to return to the level of never-smokers. A recent prospective cohort study found bladder cancer risk remains elevated for more than 32 years after quitting, even among former moderate smokers. This risk reduction is much slower than that observed for lung cancer or cardiovascular disease in former smokers.7,9,11-13

A study published this summer in the International Journal of Cancer further elucidates the association between smoking and bladder cancer. In this hospital-based, case-comparison study, data from 1,067 patients with bladder cancer (616 former smokers, 227 current smokers, 224 never-smokers) were analyzed to determine if bladder cancer in smokers had unique clinical characteristics.

In fact, at diagnosis, current smokers on average were 4 years younger and had larger (~17%) and higher (~16%) T-stage tumors compared with never-smokers (Table 2).3 In addition, muscle-invasive disease occurred significantly (P=0.002) more often in current (23%) and former smokers (24%) than never-smokers (12%).3

Table 2: Adjusted Predicted Means of Variables for Current Versus Never-Smokers With Bladder Cancer3

Smoking status Age at diagnosis (years) Grade T stage Tumor size (cm)
Never
69.7
(68.1-71.2)
2.16
(2.05-2.28)
1.56
(1.43-1.70)
2.84
(2.46-3.21)
Current 65.7
(64.2-67.2)*
2.31
(2.20-2.43)
1.81
(1.68-1.94)*
3.31
(2.95-3.68)*
*P<0.05

A second study, published last month in PLoS One, identified a single nucleotide polymorphism (SNP) in XRCC1 that appears to confer protection against bladder cancer in smokers.4 The gene is a crucial part of the base excision repair (BER) pathway, one of four major DNA repair mechanisms in humans. Because of this, SNPs in XRCC1 theoretically may influence the DNA repair function of the gene and BER pathway.4

This meta-analysis looked at studies with three relatively well-studied SNPs. The presence of the R399Q SNP in smokers (but not never-smokers) was associated with a significantly decreased risk for bladder cancer based on results of multiple studies.4 The R194W SNP and R280H SNP were associated with a significant increase in bladder cancer risk among Asian, but not other, populations, unrelated to smoking status.4 Their findings provide a rationale for further research on the influence of R399Q in smokers.

Summary

Although most bladder cancer is noninvasive, the disease is associated with high rates of recurrence despite therapy.1 Smoking is the major environmental risk factor for bladder cancer, responsible for about half of cases in both men and women. Smokers and former smokers are at higher risk than never-smokers, as evidenced in two recent studies that give more insight into the association between smoking and bladder cancer.

One study has clear clinical implications: smokers appear to be at greater risk for malignant disease and associated impacts on prognosis. They may require more aggressive treatment and follow-up regimens.3 The other identifies a SNP in the XRCC1 DNA repair gene that appears to protect smokers from developing bladder cancer. 

Further research may help establish the level of involvement for these genetic imperfections and how they may be used to improve prognosis and treatment among patients with bladder cancer and a history of smoking.

This article originally appeared on Cancer Therapy Advisor