ManageMent Update
Smoking: Its Impact on Urologic Health David Mobley, MD,1 Neil Baum, MD2 1Institute for Academic Medicine, Houston, TX; 2Department of Urology, Tulane Medical School, New Orleans, LA
Tobacco use remains the single largest preventable cause of disease and premature death in the United States, and smoking is a leading cause of cancer and death from cancer. There is also evidence that smoking is associated with several urologic diseases. Urologists have a unique opportunity to help our patients lead healthy lifestyles, which includes ending their dependence on nicotine and tobacco. This article points out the various urologic conditions associated with smoking and tobacco use with the intention of providing physicians and patients with knowledge and education regarding this connection. [Rev Urol. 2015;17(4):220-225 doi: 10.3909/riu0684]
®
© 2016 MedReviews , LLC
Key words Smoking • Bladder cancer • Prostate cancer • Kidney cancer • Erectile dysfunction • Interstitial cystitis
S
moking remains one of the greatest health threats to our nation, and the death rate among current smokers is two to three times that of nonsmokers.1 There is also evidence that smoking is associated with several urologic diseases. If we are to be effective healthcare providers, urologists must make a concerted effort to make our patients aware of the connections between tobacco and common urologic diseases. Also, urologists are in the unique position to motivate patients to stop smoking and to enter smoking cessation programs. This article
points out the various urologic conditions associated with smoking and tobacco use with the intention of providing physicians and patients with knowledge and education regarding this connection.
Smoking Statistics
Tobacco use remains the single largest preventable cause of disease and premature death in the United States, yet more than 45 million Americans still smoke cigarettes. In 2011, an estimated 19% of US adults were cigarette smokers. Today, there are an
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Smoking: Its Impact on Urologic Health estimated 1.1 billion tobacco users in the world. Tobacco use is a global epidemic, and the problem is getting worse rapidly as the tobacco industry penetrates the developing world. This number is expected to
in women.4 Each puff of smoke exposes the body to some 60 different carcinogens, and many of these are identifiable in urine specimens from smokers.5 Cigarette smoking is the major and modifiable risk fac-
Cigarette smoking triples the risk for bladder cancer when compared with the risk in nonsmokers…
increase to 1.6 billion over the next 2 decades. One person dies every 6 seconds from a tobacco-related disease. Over 20% of all deaths in the United States are from tobaccorelated diseases. Over 600,000 people die worldwide from secondhand smoke and over 200,000 of these deaths are in children. The economic cost of smoking in the United States is staggering; each pack of cigarettes sold costs society an estimated $18.05.2
Common Disease States
Smoking is a leading cause of cancer and death from cancer. It causes cancers of the lung, esophagus, larynx, mouth, throat, kidney, bladder, pancreas, stomach, and cervix, as well as acute myeloid leukemia.2 Smoking also causes heart disease, stroke, aortic aneurysm, chronic obstructive pulmonary disease (COPD), hip fractures, and cataracts. Smokers are also at higher risk of developing pneumonia and other airway infections.3
Urologic Conditions Impacted By Smoking Bladder Cancer Bladder cancer is the fifth most common solid organ cancer in Americans.4 The number of estimated new cases in the United States in 2014 was 74,690, accounting for 15,580 deaths. Of these, some 11,000 deaths occurred in men and approximately 4400
tor for development of bladder cancer in men and women. In a large study published in 2011, a number of statistics were identified regarding these issues.6 Cigarette smoking triples the risk for bladder cancer when compared with the risk in nonsmokers, with a populationattributable risk of 50% to 65% in men and 20% to 30% in women. The authors also note that incidence rates for bladder cancer have remained relatively stable over the past 3 decades in the United States. In men, the rates are 123.8 to 142.2 per 100,000 person-years, and in women, the rates are 32.5 to 33.2 per 100,000 person-years.6 In a study from Italy examining the role of cigarette smoking, the authors reported that only 13.9% of bladder cancer cases occurred in nonsmoking men; however, 63.9% of the bladder cancer cases in women were in those with no history of tobacco use, implying a distinct difference in sex risk.7 These data correlate with the data developed by Freedman and coworkers.6 Carter and coworkers1 estimated the relative risk of mortality at 3.9 (95% confidence interval [CI], 3.0-5.1) comparing nonsmokers with current smokers.1 McGrath and colleagues8 studied telomere length in men and women with bladder cancer and in healthy control subjects. Telomeres are critical in maintaining the structural integrity of the genome, and truncated telomeres are a strong characteristic of many cancers. In their
study they came to the conclusion that individuals with the shortest, or truncated, telomeres had the highest risk for development of bladder cancer.
Preventing Bladder Cancer Deaths by Not Smoking. In using
the most conservative numbers from Freedman and colleagues,6 with 50% of bladder cancers attributable to smoking in men, and 20% in women, a reduction in new cancer rates of some 30,000 per year could be achieved in the United States. Prostate Cancer Although a unifying concept as to the etiology of prostate cancer remains elusive, it may be due to myriad factors including genetics, dietary factors, infectious agents, inflammation, hormonal imbalance or exposure to toxins, such as those in cigarette smoke.9 In the study reported by Dwivedi and colleagues,9 inflammatory markers were investigated in prostate cancer patients compared with age-matched control subjects; a total of 578 men were studied. A novel cytokine interleukin (IL)-18 was evaluated; this cytokine is a measurement of proinflammatory changes. In this study the measurement of IL-18 was done by enzymelinked immunosorbent assay. IL-18 levels were significantly higher in smokers than in nonsmokers. Levels of IL-18 were also higher in patients with higher-stage disease, and were nonsignificant in those with low-stage disease. Their conclusion was that smoking increased inflammation within the prostate, increasing not only the risk of development of cancer, but of more aggressive disease as well. A report from Johns Hopkins James Brady Buchanan Urological Institute assessed risk factors for development of prostate cancer in
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Smoking: Its Impact on Urologic Health continued a total of 1544 men who underwent radical prostatectomy by Dr. Patrick Walsh. They found that cigarette smoking was the one risk factor that “stuck out like the proverbial sore thumb.” Smokers were
kidney cancer cases in the United Kingdom estimated that 29% of cases in men and 15% in women were associated with or caused by smoking.14 Kidney cancer risk is not only greater in smokers than in
Smokers were not only at greater risk for prostate cancer, but longterm smokers were at greater risk for more aggressive and more advanced disease.
not only at greater risk for prostate cancer, but long-term smokers were at greater risk for more aggressive and more advanced disease. They postulate that cigarette smoking causes oxidative damage. This, in turn, leads to free radicals which cause a buildup of toxins in the cells, increasing the risk of that organ developing cancer.10 In the report by Carter and coworkers,1 they found mortality from prostate cancer was 43% higher in current smokers. Cigarette smoking has an impact on circulating hormone levels and also increases the smoker’s exposure to known carcinogens.11 In a population-based case-control study, 753 men with prostate cancer were compared with 703 agematched controls. There was a significantly increased risk for prostate cancer in smokers (odds ratio [OR] 5 1.4, 95% CI, 1.0-2.0) compared with the nonsmoking control group. In addition, the authors found a relationship between the number of packs and years smoked and more aggressive cancers.11 Kidney Cancer Development of kidney cancer is accompanied by several risk factors, including male sex, genetic factors, age, obesity, and smoking.12 According to Cogliano and associates,13 tobacco smoking is classified as a risk for cancer in all anatomic areas of the renal upper tracts, including kidney, ureter, and renal pelvis. A review of
nonsmokers, but is also increased with the amount and duration of smoking.15 According to this same meta-analysis, the risk is 60% to 100% higher in the patients smoking 20 or more cigarettes daily compared with nonsmokers. They also found that smoking cessation, especially over 10 years, had a measurable, salutary effect on risk.15 In the study by Ross and coworkers,16 patients with a history of regular cigarette smoking had a 3.6-times increased risk of cancer of the renal pelvis and ureter; moreover, among potential risk factors for development of these cancers, cigarette smoking exceeded any other measured risk factor. Patel and
initiated in 1989. This populationbased ongoing evaluation of men included prostate diseases and voiding function, and demographic information such as smoking habits and sexual function.18 As part of this ongoing study, the results of the association between smoking and ED were assessed in 2115 white men. In men between the ages 40 and 79, smokers had an increased incidence of ED compared with never-smokers. The highest impact was seen in men in their 40s with relative odds of 2.74 (95% CI, 0.44-16.89). The impact was slightly less in subsequent decades, but overall, the ageadjusted OR was 1.42% (95% CI, 1.00-2.02). In a similar populationbased study report there was a doseresponse depending on the intensity of smoking.19 Aside from the vascular damage known to occur from cigarette smoking, other avenues are open to consideration regarding the association between smoking and ED. Smoking may impact erectile function through its potential impact of sex hormones, although
… patients with a history of regular cigarette smoking had a 3.6-times increased risk of cancer of the renal pelvis and ureter; moreover, among potential risk factors for development of these cancers, cigarette smoking exceeded any other measured risk factor.
associates17 examined the impact of smoking on histologic subtypes of renal cell carcinoma and concluded that smoking is a risk factor for clear-cell and papillary, but not for the chromophobe subtype. Erectile Dysfunction Because erectile function is a highly vascular event, and tobacco use creates a vasculopathic state in the smoker, it is no surprise that smoking and erectile dysfunction (ED) are related. In Minnesota, the Olmsted County Study of Urinary Symptoms and Health Status Among Men was
there are conflicting data. Krause and Müller,20 in a study confirmed by Svartberg and colleagues,21 found that testosterone, free testosterone, and sex hormone-binding globulin were elevated in smokers as compared with nonsmokers. However, Shaaraway and Mahmoud,22 examined not only the hormone milieu but semen parameters as well, and reported that total testosterone was lower in smokers as compared with nonsmokers. The role of the sex hormones in erectile function remains one of interest and controversy.
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Smoking: Its Impact on Urologic Health Nephrolithiasis Renal stone formation is a common condition with myriad of risk factors, including diet, genetics, obesity, medications, and geography.23 However, the role of cigarette smoking has not been extensively reviewed. In one review of 102 stone-forming patients who were compared with age-matched healthy control subjects, Tamadon and coauthors24 showed that smoking increased the risk of stone formation; 26.5% of the patients with stones were cigarette smokers, and only 14.9% in the control group were smokers (OR 5 2.06, 95% CI, 1.06-4.01; P 5 .034). The population was not large, but the results were statistically significant. Liu and coworkers25 also reported that cigarette smoking was an independent risk factor for calcium stone formation. There are contrasting data showing lack of support for a connection between smoking and nephrolithiasis. Słojewski and colleagues26 and Hirvonen and colleagues27 found the link to be weak; several theories have been proposed for the relationship between cigarette smoking as a risk factor for stone formation, includ-
(P 5 .000009) contributed to the risk of stress, but not urge incontinence, and was not influenced by age, weight, pregnancy, or menopause. The OR for genuine stress incontinence was 2.20 for former smokers and 2.48 for current smokers.30 Diokno and coworkers31 found urinary incontinence to be tied closely to age and the presence of COPD, and therefore more common in women over age 60 years, in whom COPD has had time to
smoking can lead to menstrual disorders and have an adverse effect on the onset of menopause.
progress to a chronic cough. This would lend credence to the theory postulated by Bump and McClish30 that chronic coughing in the elderly COPD patient could cause anatomic and pressure changes in the continence mechanism. One study examining urodynamic factors in smokers found the maximal intravesical peak pressure generated by a cough to be higher in smokers compared with nonsmokers.32 The American Urological Association Healthcare Provider Pocket Guide points out the impact of lifestyle changes for incontinent patients,
… several theories have been proposed for the relationship between cigarette smoking as a risk factor for stone formation, including decreasing of urinary output, oxidative stress, and an increase in nucleation, aggregation, and crystal formation in the kidneys.
ing decreasing of urinary output, oxidative stress, and an increase in nucleation, aggregation, and crystal formation in the kidneys.28,29 Incontinence In a large case-control study, Bump and McClish30 evaluated the relationship between smoking and urinary incontinence in women. This study included over 600 women, approximately half of whom were incontinent and half of whom were continent. Smoking significantly
that have been studied by comparing smoking with nonsmoking populations. Smoking has always been strongly discouraged during pregnancy, as studies over many years have shown the potential fetal damage from smoking during pregnancy. The dangers to the developing fetus include growth retardation, fetal death, premature delivery, lactation problems, and long-term effects on the child.35 In addition to these issues, smoking
and, with regard to smoking, states that “…smoking cessation is critical in reducing chronic cough which results in pressure on the pelvic floor muscles.”33 Infertility A number of studies have examined the impact of smoking on fertility in both men and women. For a comprehensive review of the literature on this subject, refer to the review article by Mostafa.34 Herein we report the aspects of fertility
can lead to menstrual disorders and have an adverse effect on the onset of menopause.36 Curtis and coworkers37 examined the monthly probability of conception in 2607 planned pregnancies and found smoking to have a detrimental effect on fecundity. Success from in vitro fertilization has been found to be diminished if either the male or female partner is a smoker.37 Alterations in semen parameters, especially motility and morphology, have been documented in multiple studies.34,38,39 Benign Prostatic Hyperplasia and Prostate-specific Antigen The relationship between benign prostatic hyperplasia (BPH) and the hormone milieu was studied by Küpeli and colleagues 40 in 1997. They evaluated 68 men with BPH. The mean age was 59 years (range, 52-74 y); prostate volume and hormones were measured, including estradiol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), and testosterone. Mean prostate volume was larger in nonsmokers than in smokers. Estradiol levels were significantly higher in smokers. There were no significant differences in testosterone, DHEA, or DHEAS levels in
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Smoking: Its Impact on Urologic Health continued smokers versus nonsmokers. The authors concluded that the impact of smoking, especially the differences in estradiol, might contribute to the smaller prostate glands found in smokers. They also found a slight increase in BPH symptoms in nonsmokers.40 The effect of cigarette smoking on prostatespecific antigen (PSA) levels in two age groups was evaluated by Koc and associates.41 They arrived at essentially the same conclusions as Küpeli and colleagues 40 with regard to the hormone environment in smokers versus nonsmokers. Their studies included two age groups: those aged 25 to 35 years and those aged 50 to 70 years. They evaluated data on a total of 388 men and found PSA levels to be higher in the smokers, but the difference was not statistically significant.41 Interstitial Cystitis Interstitial cystitis (IC) is a chronic, painful bladder and pelvic syndrome of undetermined etiology. According to an Austrian survey, IC is thought to have an incidence in the population of from 30 to
46 per 10,000 women.42 An estimate from the National Kidney Foundation in the United States suggests that 700,000 to 1 million American women are affected.43 Although a review of the research literature does not reveal any studies directly relating cigarette smoking as a risk factor or etiologic agent for IC, the “help literature” is replete with advice to women with IC to cease tobacco use, as it may aggravate the symptoms. In a National Kidney Foundation guide, cigarette smoking is identified as an aggravating factor for symptoms of IC. In materials produced by the Interstitial Cystitis Association, they recommend ceasing smoking, as the chemicals in cigarette smoke may be an irritant to the symptoms of IC.44 The International Urogynecological Association makes the same recommendation, stating that smoking should be included as a bladder irritant in IC patients.45 In the Austrian study of 981 subjects, approximately 31% of patients in the 20 to 59-year age group were smokers, and those women had the highest prevalence of more severe symptoms.42
Conclusions
Physicians have known for decades that there is a relationship between lung cancer and cardiovascular disease and smoking. Now the healthcare profession has connected various urologic diseases and smoking. Therefore, urologists should make every effort to ensure that patients are aware of this relationship and motivate them to participate in a smoking cessation program as part of their treatment. Quitting smoking reduces the health risks caused by exposure to tobacco smoke. Regardless of age, smokers can substantially reduce their risk of disease, including cancer, by quitting. Urologists have a unique opportunity to help our patients lead healthy lifestyles, which includes ending their dependence on nicotine and tobacco. References 1.
2.
3.
Carter BD, Abnet CC, Feskanich D, et al. Smoking and mortality-beyond established causes. N Engl J Med. 2015;372:631-640. Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults - United States, 2011. MMWR Morb Mortal Wkly Rep. 2012;61:889-894. US Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. A
Main Points • Smoking is a leading cause of cancer and death from cancer. There is evidence that smoking is associated with several urologic diseases. • Bladder cancer is the fifth most common solid organ cancer in Americans. Cigarette smoking is the major and most modifiable risk factor for development of bladder cancer in men and women, and smoking triples the risk for bladder cancer when compared with the risk in nonsmokers. • Smoking is classified as a risk for cancer in all anatomic areas of the renal upper tracts, including kidney, ureter, and renal pelvis. Kidney cancer risk is not only greater in smokers than in nonsmokers, but is also increased with the amount and duration of smoking. • Cigarette smoking has been found to have a negative impact on continence and fertility, and aggravates symptoms of interstitial cystitis. • Urologists should make every effort to ensure that patients are aware of the relationship between smoking and urologic disease, and motivate them to participate in a smoking cessation program as part of their treatment.
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Smoking: Its Impact on Urologic Health
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Report of the Surgeon General. Atlanta, GA: Centers for Disease Control and Prevention; 2010. cancer.gov Manatonski GM, Elliott EA. Bladder cancer epidemiology. Epidemiol Rev. 1981;3:203-229. Freedman ND, Silverman DT, Hollenbeck AR, et al. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011;306: 737-745. La Vecchia C, Negri E, D’Avanzo B, et al. Genital and urinary tract diseases and bladder cancer. Cancer Res. 1991;51:629-631. McGrath M, Wong JY, Michaud D, et al. Telomere length, cigarette smoking and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. 2007;16:815-819. Dwivedi S, Goel A, Mandhani A, et al. Tobacco exposure may enhance inflammation in prostate cancer patients: an exploratory study in north Indian population. Toxicol Int. 2012;19:310-318. Prostate cancer is worse in men who smoke. Prostate Cancer Update. The James Buchanan Brady Urological Institute website. http://urology.jhu.edu/newsletter/ prostate_cancer612.php. Accessed October 21, 2015. Plaskon LA, Penson DF, Vaughan TL, Stanford JL. Cigarette smoking and risk of prostate cancer in middle-aged men. Cancer Epidemiol Biomarkers Prev. 2003;12:604-609. Parkin DM, Boyd L, Walker LC. 16. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer. 2011;105(suppl 2):S77-S81. Cogliano VJ, Baan R, Straif K, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst. 2011;103:1827-1839. Parkin DM. 2. Tobacco-attributable cancer burden in the UK in 2010. Br J Cancer. 2011;195(suppl 2):S6-S13. Hunt JD, van der Hel OL, McMillan GP, et al. Renal cell carcinoma in relation to cigarette smoking: metaanalysis of 24 studies. Int J Cancer. 2005;114:101-108. Ross RK, Paganini-Hill A, Landolph J, et al. Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter. Cancer Res. 1989;49:1045-1048. Patel NH, Attwood KM, Hanzly M, et al. Comparative analysis of smoking as risk factor among renal cell carcinoma histological subtypes. J Urol. 2015;194: 640-646.
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Jacobsen SJ, Guess HA, Panser L, et al. A populationbased study of health-care seeking behavior for treatment of urinary symptoms. The Olmsted County Study of Urinary Symptoms and Health Status Among Men. Arch Fam Med. 1993;2:729-735. Gades NM, Nehra A, Jacobsen DJ, et al. Association between smoking and erectile dysfunction: a population-based study. Am J Epidemiol. 2005;161:346-351. Krause W, Müller HH. Relation of sexual dysfunction to hormone levels, diseases and drugs used in andrological patients. Urol Int. 2000;64:143-148. Svartberg J, Midtby M, Bønaa KH, et al. The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Eur J Endocrinol. 2003;149:145-152. Shaaraway M, Mahmoud KZ. Endocrine profile and semen characteristics in male smokers. Fertil Steril. 1982;38:255-257. Hall PM. Nephrolithiasis: treatment, causes and prevention. Cleve Clin J Med. 2009;76:583-591. Tamadon MR, Nassaii M, Ghorbani, R. Cigarette smoking and nephrolithiasis in adult individuals. Nephrourol Mon. 2013;5:702-705. Liu CC, Huang SP, Wu WJ, et al. The impact of cigarette smoking, alcohol drinking and betel quid chewing on the risk of calcium urolithiasis. Ann Epidemiol. 2009;19:539-545. Słojewski M, Czerny B, Safranow K, et al. Does smoking have any effect on urinary stone composition and the distribution of trace elements in urine and stones? Urol Res. 2009;37:317-322. Hirvonen T, Pietinen P, Virtanen M, et al. Nutrient intake and use of beverages and the risk of kidney stones among male smokers. Am J Epidemiol. 1999;150:187-194. Robert M, Roux JO, Bourelly F, et al. Circadian variations in the risk of urinary calcium oxalate stone formation. Br J Urol. 1994;74:294-297. Obata T, Tomaru K, Nagakura T, et al. Smoking and oxidative stress: assay of isoprostane in human urine by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000;746:11-15. Bump RC, McClish DK. Cigarette smoking and urinary incontinence in women. Am J Obstet Gynecol. 1992;167:1213-1218. Diokno AC, Brock BM, Herzog AR, Bromberg J. Medical correlates of urinary incontinence in the elderly. Urology. 1990;36:129-138.
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Fuganti PE, Gowdy JM, Santiago NC. Obesity and smoking: are they modulators of cough, intravesical peak pressure, and stress urinary incontinence? Int Braz J Urol. 2011;37:528-533. A patient’s guide: 1 in 3 women experience stress urinary incontinence. American Urological Association website. https://www.auanet.org/common/pdf/ products/SUIPatientGuide.pdf. Accessed October 21, 2015. Mostafa T. Cigarette smoking and male infertility. J Advanced Res. 2010;1:179-186. Sépaniak S, Forges T, Monnier-Barbarino P. Cigarette smoking and fertility in women and men [in French]. Gynecol Obstet Fertil. 2006;34:945-949. Soares SR, Melo MA. Cigarette smoking and reproductive function. Curr Opin Obstet Gynecol. 2008;20:281-291. Curtis KM, Savitz DA, Arbuckle TE. Effects of cigarette smoking, caffeine consumption and alcohol intake on fecundability. Am J Epidemiol. 1997;1461:32-41. Shaaraway M, Mahmoud KZ. Endocrine profile and semen characteristics in male smokers. Fertil Steril. 1982;38:255-257. Chia SE, Ong CN, Tsakok FM. Effects of cigarette smoking on human semen quality. Arch Androl. 1994;33:163-168. Küpeli B, Soygür T, Aydos K, et al. The role of cigarette smoking in prostatic enlargement. Br J Urol. 1997;80:201-204. Koc G, Akgul K, Yilmaz Y, et al. The effects of cigarette smoking on prostate-specific antigen in two different age groups. Can Urol Assoc J. 2013;7:E704-E707. Temml C, Wehrberger C, Riedl C, et al. Prevalence and correlates for interstitial cystitis symptoms in women participating in a health screening project. Eur Urol. 2007;51:803-808. Interstitial cystitis. National Kidney Foundation website. www.kidney.org/atoz/content/interstitial.cfm. Accessed October 21, 2015. Quitting smoking. Interstitial Cystitis Association website. http://www.ichelp.org/page.aspx?pid5931. Accessed October 21, 2015. International Urogynecological Association. Interstitial Cystitis & Painful Bladder Syndrome: A Guide for Women. Washington, DC: International Urogynecoligal Association; 2011. c.ymcdn.com/sites/www.iuga. org/resource/resmgr/brochures/eng_interstitialcyst. pdf
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Smoking: Its Impact on Urologic Health David Mobley, MD,1 Neil Baum, MD2 1Institute for Academic Medicine, Houston, TX; 2Department of Urology, Tulane Medical School, New Orleans, LA
Tobacco use remains the single largest preventable cause of disease and premature death in the United States, and smoking is a leading cause of cancer and death from cancer. There is also evidence that smoking is associated with several urologic diseases. Urologists have a unique opportunity to help our patients lead healthy lifestyles, which includes ending their dependence on nicotine and tobacco. This article points out the various urologic conditions associated with smoking and tobacco use with the intention of providing physicians and patients with knowledge and education regarding this connection. [Rev Urol. 2015;17(4):220-225 doi: 10.3909/riu0684]
®
© 2016 MedReviews , LLC
Key words Smoking • Bladder cancer • Prostate cancer • Kidney cancer • Erectile dysfunction • Interstitial cystitis
S
moking remains one of the greatest health threats to our nation, and the death rate among current smokers is two to three times that of nonsmokers.1 There is also evidence that smoking is associated with several urologic diseases. If we are to be effective healthcare providers, urologists must make a concerted effort to make our patients aware of the connections between tobacco and common urologic diseases. Also, urologists are in the unique position to motivate patients to stop smoking and to enter smoking cessation programs. This article
points out the various urologic conditions associated with smoking and tobacco use with the intention of providing physicians and patients with knowledge and education regarding this connection.
Smoking Statistics
Tobacco use remains the single largest preventable cause of disease and premature death in the United States, yet more than 45 million Americans still smoke cigarettes. In 2011, an estimated 19% of US adults were cigarette smokers. Today, there are an
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Smoking: Its Impact on Urologic Health estimated 1.1 billion tobacco users in the world. Tobacco use is a global epidemic, and the problem is getting worse rapidly as the tobacco industry penetrates the developing world. This number is expected to
in women.4 Each puff of smoke exposes the body to some 60 different carcinogens, and many of these are identifiable in urine specimens from smokers.5 Cigarette smoking is the major and modifiable risk fac-
Cigarette smoking triples the risk for bladder cancer when compared with the risk in nonsmokers…
increase to 1.6 billion over the next 2 decades. One person dies every 6 seconds from a tobacco-related disease. Over 20% of all deaths in the United States are from tobaccorelated diseases. Over 600,000 people die worldwide from secondhand smoke and over 200,000 of these deaths are in children. The economic cost of smoking in the United States is staggering; each pack of cigarettes sold costs society an estimated $18.05.2
Common Disease States
Smoking is a leading cause of cancer and death from cancer. It causes cancers of the lung, esophagus, larynx, mouth, throat, kidney, bladder, pancreas, stomach, and cervix, as well as acute myeloid leukemia.2 Smoking also causes heart disease, stroke, aortic aneurysm, chronic obstructive pulmonary disease (COPD), hip fractures, and cataracts. Smokers are also at higher risk of developing pneumonia and other airway infections.3
Urologic Conditions Impacted By Smoking Bladder Cancer Bladder cancer is the fifth most common solid organ cancer in Americans.4 The number of estimated new cases in the United States in 2014 was 74,690, accounting for 15,580 deaths. Of these, some 11,000 deaths occurred in men and approximately 4400
tor for development of bladder cancer in men and women. In a large study published in 2011, a number of statistics were identified regarding these issues.6 Cigarette smoking triples the risk for bladder cancer when compared with the risk in nonsmokers, with a populationattributable risk of 50% to 65% in men and 20% to 30% in women. The authors also note that incidence rates for bladder cancer have remained relatively stable over the past 3 decades in the United States. In men, the rates are 123.8 to 142.2 per 100,000 person-years, and in women, the rates are 32.5 to 33.2 per 100,000 person-years.6 In a study from Italy examining the role of cigarette smoking, the authors reported that only 13.9% of bladder cancer cases occurred in nonsmoking men; however, 63.9% of the bladder cancer cases in women were in those with no history of tobacco use, implying a distinct difference in sex risk.7 These data correlate with the data developed by Freedman and coworkers.6 Carter and coworkers1 estimated the relative risk of mortality at 3.9 (95% confidence interval [CI], 3.0-5.1) comparing nonsmokers with current smokers.1 McGrath and colleagues8 studied telomere length in men and women with bladder cancer and in healthy control subjects. Telomeres are critical in maintaining the structural integrity of the genome, and truncated telomeres are a strong characteristic of many cancers. In their
study they came to the conclusion that individuals with the shortest, or truncated, telomeres had the highest risk for development of bladder cancer.
Preventing Bladder Cancer Deaths by Not Smoking. In using
the most conservative numbers from Freedman and colleagues,6 with 50% of bladder cancers attributable to smoking in men, and 20% in women, a reduction in new cancer rates of some 30,000 per year could be achieved in the United States. Prostate Cancer Although a unifying concept as to the etiology of prostate cancer remains elusive, it may be due to myriad factors including genetics, dietary factors, infectious agents, inflammation, hormonal imbalance or exposure to toxins, such as those in cigarette smoke.9 In the study reported by Dwivedi and colleagues,9 inflammatory markers were investigated in prostate cancer patients compared with age-matched control subjects; a total of 578 men were studied. A novel cytokine interleukin (IL)-18 was evaluated; this cytokine is a measurement of proinflammatory changes. In this study the measurement of IL-18 was done by enzymelinked immunosorbent assay. IL-18 levels were significantly higher in smokers than in nonsmokers. Levels of IL-18 were also higher in patients with higher-stage disease, and were nonsignificant in those with low-stage disease. Their conclusion was that smoking increased inflammation within the prostate, increasing not only the risk of development of cancer, but of more aggressive disease as well. A report from Johns Hopkins James Brady Buchanan Urological Institute assessed risk factors for development of prostate cancer in
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Smoking: Its Impact on Urologic Health continued a total of 1544 men who underwent radical prostatectomy by Dr. Patrick Walsh. They found that cigarette smoking was the one risk factor that “stuck out like the proverbial sore thumb.” Smokers were
kidney cancer cases in the United Kingdom estimated that 29% of cases in men and 15% in women were associated with or caused by smoking.14 Kidney cancer risk is not only greater in smokers than in
Smokers were not only at greater risk for prostate cancer, but longterm smokers were at greater risk for more aggressive and more advanced disease.
not only at greater risk for prostate cancer, but long-term smokers were at greater risk for more aggressive and more advanced disease. They postulate that cigarette smoking causes oxidative damage. This, in turn, leads to free radicals which cause a buildup of toxins in the cells, increasing the risk of that organ developing cancer.10 In the report by Carter and coworkers,1 they found mortality from prostate cancer was 43% higher in current smokers. Cigarette smoking has an impact on circulating hormone levels and also increases the smoker’s exposure to known carcinogens.11 In a population-based case-control study, 753 men with prostate cancer were compared with 703 agematched controls. There was a significantly increased risk for prostate cancer in smokers (odds ratio [OR] 5 1.4, 95% CI, 1.0-2.0) compared with the nonsmoking control group. In addition, the authors found a relationship between the number of packs and years smoked and more aggressive cancers.11 Kidney Cancer Development of kidney cancer is accompanied by several risk factors, including male sex, genetic factors, age, obesity, and smoking.12 According to Cogliano and associates,13 tobacco smoking is classified as a risk for cancer in all anatomic areas of the renal upper tracts, including kidney, ureter, and renal pelvis. A review of
nonsmokers, but is also increased with the amount and duration of smoking.15 According to this same meta-analysis, the risk is 60% to 100% higher in the patients smoking 20 or more cigarettes daily compared with nonsmokers. They also found that smoking cessation, especially over 10 years, had a measurable, salutary effect on risk.15 In the study by Ross and coworkers,16 patients with a history of regular cigarette smoking had a 3.6-times increased risk of cancer of the renal pelvis and ureter; moreover, among potential risk factors for development of these cancers, cigarette smoking exceeded any other measured risk factor. Patel and
initiated in 1989. This populationbased ongoing evaluation of men included prostate diseases and voiding function, and demographic information such as smoking habits and sexual function.18 As part of this ongoing study, the results of the association between smoking and ED were assessed in 2115 white men. In men between the ages 40 and 79, smokers had an increased incidence of ED compared with never-smokers. The highest impact was seen in men in their 40s with relative odds of 2.74 (95% CI, 0.44-16.89). The impact was slightly less in subsequent decades, but overall, the ageadjusted OR was 1.42% (95% CI, 1.00-2.02). In a similar populationbased study report there was a doseresponse depending on the intensity of smoking.19 Aside from the vascular damage known to occur from cigarette smoking, other avenues are open to consideration regarding the association between smoking and ED. Smoking may impact erectile function through its potential impact of sex hormones, although
… patients with a history of regular cigarette smoking had a 3.6-times increased risk of cancer of the renal pelvis and ureter; moreover, among potential risk factors for development of these cancers, cigarette smoking exceeded any other measured risk factor.
associates17 examined the impact of smoking on histologic subtypes of renal cell carcinoma and concluded that smoking is a risk factor for clear-cell and papillary, but not for the chromophobe subtype. Erectile Dysfunction Because erectile function is a highly vascular event, and tobacco use creates a vasculopathic state in the smoker, it is no surprise that smoking and erectile dysfunction (ED) are related. In Minnesota, the Olmsted County Study of Urinary Symptoms and Health Status Among Men was
there are conflicting data. Krause and Müller,20 in a study confirmed by Svartberg and colleagues,21 found that testosterone, free testosterone, and sex hormone-binding globulin were elevated in smokers as compared with nonsmokers. However, Shaaraway and Mahmoud,22 examined not only the hormone milieu but semen parameters as well, and reported that total testosterone was lower in smokers as compared with nonsmokers. The role of the sex hormones in erectile function remains one of interest and controversy.
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Smoking: Its Impact on Urologic Health Nephrolithiasis Renal stone formation is a common condition with myriad of risk factors, including diet, genetics, obesity, medications, and geography.23 However, the role of cigarette smoking has not been extensively reviewed. In one review of 102 stone-forming patients who were compared with age-matched healthy control subjects, Tamadon and coauthors24 showed that smoking increased the risk of stone formation; 26.5% of the patients with stones were cigarette smokers, and only 14.9% in the control group were smokers (OR 5 2.06, 95% CI, 1.06-4.01; P 5 .034). The population was not large, but the results were statistically significant. Liu and coworkers25 also reported that cigarette smoking was an independent risk factor for calcium stone formation. There are contrasting data showing lack of support for a connection between smoking and nephrolithiasis. Słojewski and colleagues26 and Hirvonen and colleagues27 found the link to be weak; several theories have been proposed for the relationship between cigarette smoking as a risk factor for stone formation, includ-
(P 5 .000009) contributed to the risk of stress, but not urge incontinence, and was not influenced by age, weight, pregnancy, or menopause. The OR for genuine stress incontinence was 2.20 for former smokers and 2.48 for current smokers.30 Diokno and coworkers31 found urinary incontinence to be tied closely to age and the presence of COPD, and therefore more common in women over age 60 years, in whom COPD has had time to
smoking can lead to menstrual disorders and have an adverse effect on the onset of menopause.
progress to a chronic cough. This would lend credence to the theory postulated by Bump and McClish30 that chronic coughing in the elderly COPD patient could cause anatomic and pressure changes in the continence mechanism. One study examining urodynamic factors in smokers found the maximal intravesical peak pressure generated by a cough to be higher in smokers compared with nonsmokers.32 The American Urological Association Healthcare Provider Pocket Guide points out the impact of lifestyle changes for incontinent patients,
… several theories have been proposed for the relationship between cigarette smoking as a risk factor for stone formation, including decreasing of urinary output, oxidative stress, and an increase in nucleation, aggregation, and crystal formation in the kidneys.
ing decreasing of urinary output, oxidative stress, and an increase in nucleation, aggregation, and crystal formation in the kidneys.28,29 Incontinence In a large case-control study, Bump and McClish30 evaluated the relationship between smoking and urinary incontinence in women. This study included over 600 women, approximately half of whom were incontinent and half of whom were continent. Smoking significantly
that have been studied by comparing smoking with nonsmoking populations. Smoking has always been strongly discouraged during pregnancy, as studies over many years have shown the potential fetal damage from smoking during pregnancy. The dangers to the developing fetus include growth retardation, fetal death, premature delivery, lactation problems, and long-term effects on the child.35 In addition to these issues, smoking
and, with regard to smoking, states that “…smoking cessation is critical in reducing chronic cough which results in pressure on the pelvic floor muscles.”33 Infertility A number of studies have examined the impact of smoking on fertility in both men and women. For a comprehensive review of the literature on this subject, refer to the review article by Mostafa.34 Herein we report the aspects of fertility
can lead to menstrual disorders and have an adverse effect on the onset of menopause.36 Curtis and coworkers37 examined the monthly probability of conception in 2607 planned pregnancies and found smoking to have a detrimental effect on fecundity. Success from in vitro fertilization has been found to be diminished if either the male or female partner is a smoker.37 Alterations in semen parameters, especially motility and morphology, have been documented in multiple studies.34,38,39 Benign Prostatic Hyperplasia and Prostate-specific Antigen The relationship between benign prostatic hyperplasia (BPH) and the hormone milieu was studied by Küpeli and colleagues 40 in 1997. They evaluated 68 men with BPH. The mean age was 59 years (range, 52-74 y); prostate volume and hormones were measured, including estradiol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), and testosterone. Mean prostate volume was larger in nonsmokers than in smokers. Estradiol levels were significantly higher in smokers. There were no significant differences in testosterone, DHEA, or DHEAS levels in
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Smoking: Its Impact on Urologic Health continued smokers versus nonsmokers. The authors concluded that the impact of smoking, especially the differences in estradiol, might contribute to the smaller prostate glands found in smokers. They also found a slight increase in BPH symptoms in nonsmokers.40 The effect of cigarette smoking on prostatespecific antigen (PSA) levels in two age groups was evaluated by Koc and associates.41 They arrived at essentially the same conclusions as Küpeli and colleagues 40 with regard to the hormone environment in smokers versus nonsmokers. Their studies included two age groups: those aged 25 to 35 years and those aged 50 to 70 years. They evaluated data on a total of 388 men and found PSA levels to be higher in the smokers, but the difference was not statistically significant.41 Interstitial Cystitis Interstitial cystitis (IC) is a chronic, painful bladder and pelvic syndrome of undetermined etiology. According to an Austrian survey, IC is thought to have an incidence in the population of from 30 to
46 per 10,000 women.42 An estimate from the National Kidney Foundation in the United States suggests that 700,000 to 1 million American women are affected.43 Although a review of the research literature does not reveal any studies directly relating cigarette smoking as a risk factor or etiologic agent for IC, the “help literature” is replete with advice to women with IC to cease tobacco use, as it may aggravate the symptoms. In a National Kidney Foundation guide, cigarette smoking is identified as an aggravating factor for symptoms of IC. In materials produced by the Interstitial Cystitis Association, they recommend ceasing smoking, as the chemicals in cigarette smoke may be an irritant to the symptoms of IC.44 The International Urogynecological Association makes the same recommendation, stating that smoking should be included as a bladder irritant in IC patients.45 In the Austrian study of 981 subjects, approximately 31% of patients in the 20 to 59-year age group were smokers, and those women had the highest prevalence of more severe symptoms.42
Conclusions
Physicians have known for decades that there is a relationship between lung cancer and cardiovascular disease and smoking. Now the healthcare profession has connected various urologic diseases and smoking. Therefore, urologists should make every effort to ensure that patients are aware of this relationship and motivate them to participate in a smoking cessation program as part of their treatment. Quitting smoking reduces the health risks caused by exposure to tobacco smoke. Regardless of age, smokers can substantially reduce their risk of disease, including cancer, by quitting. Urologists have a unique opportunity to help our patients lead healthy lifestyles, which includes ending their dependence on nicotine and tobacco. References 1.
2.
3.
Carter BD, Abnet CC, Feskanich D, et al. Smoking and mortality-beyond established causes. N Engl J Med. 2015;372:631-640. Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults - United States, 2011. MMWR Morb Mortal Wkly Rep. 2012;61:889-894. US Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. A
Main Points • Smoking is a leading cause of cancer and death from cancer. There is evidence that smoking is associated with several urologic diseases. • Bladder cancer is the fifth most common solid organ cancer in Americans. Cigarette smoking is the major and most modifiable risk factor for development of bladder cancer in men and women, and smoking triples the risk for bladder cancer when compared with the risk in nonsmokers. • Smoking is classified as a risk for cancer in all anatomic areas of the renal upper tracts, including kidney, ureter, and renal pelvis. Kidney cancer risk is not only greater in smokers than in nonsmokers, but is also increased with the amount and duration of smoking. • Cigarette smoking has been found to have a negative impact on continence and fertility, and aggravates symptoms of interstitial cystitis. • Urologists should make every effort to ensure that patients are aware of the relationship between smoking and urologic disease, and motivate them to participate in a smoking cessation program as part of their treatment.
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