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Sexx Matters

Smoking and Nonrespiratory Cancers in Women

Kristen Ricchetti; Eileen Resnick, PhD; Viviana Simon, PhD; Jennifer Wider, MD

While most women know about the link between smoking and lung cancer, they are not aware of the connection to cervical and bladder cancers„and knowing this information may provide extra motivation to quit.

Smoking is the leading preventable cause of disease and death in the United States today. One in five US women are smokers.1 Fifty percent of smokers will die from causes directly linked to smoking, losing an average of 12 years of life compared with nonsmokers. Nonsmokers who are exposed to secondhand smoke also have increased morbidity and mortality risks, with 38,000 deaths annually resulting from secondhand smoke.1

Most individuals are aware of smoking as a cause of respiratory cancers and coronary heart disease, but few realize that smoking is a significant risk factor for emphysema, chronic bronchitis, stroke, hypertension, osteoporosis, and reproductive problems. Smoking also increases the risk for nonrespiratory cancers, including cancers of the esophagus, stomach, liver, pancreas, bladder, kidney, and cervix.1 Thus, although 99% of women surveyed were aware of smoking-related respiratory disease, only 22% were aware of increased risks of infertility, 30% of osteoporosis, 17% of early menopause, and 24% of cervical cancer.2 The effects of smoking vary by gender, and both bladder and cervical cancers are considered preventable diseases; the direct link to smoking and lifestyle makes the annual deaths caused by these cancers particularly tragic.

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CERVICAL CANCER

Women who smoke or who are exposed to secondhand smoke have a 2.6-fold to 4.3-fold higher adjusted relative risk of developing cervical abnormalities.3-6 By the same token though, smoking cessation can reduce the lesion size of low-grade cervical abnormalities.7-9

The American Cancer Society estimates that 9,710 new cases of cervical cancer will be diagnosed and 3,700 women will die from it in 2006.1 While certain subtypes of sexually transmitted human papillomavirus (HPV) have been identified as the primary cause of cervical cancer, HPV infection alone may not be sufficient to cause neoplastic conversion of cervical cells. A recent study showed that HPV-positive women who were smokers or ex-smokers had an increased risk of developing invasive squamous cell cervical carcinoma.10 In fact, the chemicals in tobacco smoke may compromise the cellular milieu of the cervix. For example, cervical epithelial cells have been shown to metabolize the tobacco-specific nitrosamines using various pathways that result in the formation of active carcinogenic intermediate products.11,12The prolonged presence of these compounds produces DNA adducts that may contribute to the development of lesions and neoplasia. Moreover, cervical cancer is associated with smoking independent of HPV infection, age of first intercourse, or number of sexual partners.13,14

Cervical cancer is a largely preventable disease using routine screening with the Papanicolaou (Pap) smear or the DNA-based HPV test. When detected early, it is amenable to management with treatments matched to the stage of disease progression.15 Today, nearly 100% of patients diagnosed in the preinvasive stages survive; nine out of 10 women with invasive cervical cancer survive for the first year postdiagnosis, and 73% survive for 5 years. The overall 5-year survival rate is remarkably high at 92% for localized cases.1 In smokers infected with high-risk HPV subtypes, however, early-stage cervical cancer is associated with decreased survival.16

The US Food and Drug Administration (FDA) recently approved an HPV vaccine for prevention of cervical cancer. By targeting the specific HPV subtypes that cause cervical cancer, this new vaccine is slated for use in children before they become sexually active. Development and approval of this vaccine represent a powerful medical advance, and one that has potential to eliminate cervical cancer in the future.

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BLADDER CANCER

Bladder cancer accounts for 90% of urinary tract cancers. Cancers of the renal parenchyma, renal pelvis, and the ureter all have higher incidences in men than women, but women have higher death rates.1 Smoking increases risks for all urinary tract cancers, even among ex-smokers, and may account for 30% to 40% of all US cases of bladder cancer.17 In a study of more than 1,500 patients, the risk of bladder cancer was higher in women than men who smoked comparable amounts of cigarettes. For the heaviest smokers (40 cigarettes per day for 40 years), the women’s risk of bladder cancer was 2-fold higher than that in the men.18

In 2006, approximately 45,000 men and 17,000 women will be diagnosed with bladder cancer.1 Smoking is the greatest risk factor for this disease, causing 48% of bladder cancer deaths in men and 28% in women. The incidence of bladder cancer increases with age; after age 70 years, the incidence is 2-fold to 3-fold higher compared with age 55 to 69 years, and 15-fold to 20-fold higher compared with age 30 to 54 years.17

Carcinogens in cigarette smoke are absorbed from the lungs into the bloodstream, filtered by the kidneys, and concentrated in the urine. Chemicals in the urine can damage the urothelial cells that line the bladder. Occupational exposures to aromatic amines found in some dyes, paints, solvents, leather dust, inks, combustion products, rubbers, and textiles increase the risk of bladder cancer in the same way.19 Hairdressers, machinists, painters, printers, truck drivers, and those who work with the drugs used in chemotherapy are at increased risk as well.

Cigarette smoke is a rich source of arylamines, which are metabolized by the N-acetyltransferase (NAT)-2 enzyme and activated by the NAT-1 enzyme to highly reactive species that can form DNA adducts. The xeroderma pigmentosum genes XPD and XPB are part of the nucleotide excision repair pathway, which mediates DNA repair. Certain polymorphisms have been described in these enzymes that may be associated with increased bladder cancer risks in smokers.20,21 Polymorphisms in another metabolic enzyme, glutathione-S-transferase M1, increases the risk of bladder cancer in female smokers but not in male smokers, regardless of smoking habits.22 Finally, mutations that inactivate the tumor suppressor gene are highly prevalent among bladder cancer patients,21 and these mutations are found more frequently in tumors of smokers and ex-smokers than nonsmokers.23

Detection of bladder cancer in women tends to be delayed be-cause the symptoms (hematuria, dysuria) are similar to those of urinary tract infection.24 More than 90% of bladder cancers are transitional cell carcinomas originating in bladder epithelium. Tumors are categorized as low-grade (superficial) or high-grade (muscle invasive),25 and women may progress to the muscle-invasive stage more often than men (85.2% and 50.7%, respectively).26

There is no means of routine screening, but early detection of bladder cancer improves prognosis, quality of life, and survival. Although men are about four times more likely to develop bladder cancer than women, women have a 30% to 50% greater risk of mortality—possibly due to more advanced disease at diagnosis.27 For patients diagnosed with superficial, non-muscle-invasive bladder cancer, the 5-year survival rate is 94%. By contrast, the 5-year survival rate for bladder cancers that spread over the pelvic region is 49%, while progression to other organs reduces this figure to 6%.1

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DISCUSSION

Men and women may start smoking for different reasons. Men initiate smoking to boost energy, whereas women often start smoking for stress reduction.28,29 Young women frequently cite weight control as a motivating factor. Although fewer adult women smoke than men, the number of male smokers is declining faster than the number of female smokers.30,31 Social and physiologic responses to smoking differ between the sexes, but 79% of women surveyed did not know that there were gender differences with regard to smoking and its health effects.2

Reduction of health risks by smoking cessation varies across medical conditions. Risk reduction for lung diseases and various cancers accrues gradually. Significant risk reduction for cancers after cessation can be seen at 5 to 15 years, although the risk generally does not appear to reach the level of nonsmokers. In those with smoking-related diseases, cessation can improve prognosis, response to medication, and quality of life.32

Nonetheless, only 33% of women have discussed smoking with a health care professional, even though more than 50% of this group regarded such clinicians as their principal source of health information.33 Awareness is also a problem among medical professionals; while more than 90% of nurses interviewed knew that a history of sexually transmitted infections, early age of first sexual encounter, and multiple sex partners put women at higher risk for cervical cancer, fewer than 55% listed smoking as a preventable risk factor.34

Clinical practice guidelines suggest that clinicians should document their patients’ smoking status, assess willingness to quit, and provide information, referrals, and medication.35 Follow-up is crucial. Several antismoking treatments have been proved effective, including nicotine replacement therapy (gum, inhaler, patch, nasal spray) and oral nonnicotine agents (bupropion, doxepin, nortriptyline).36-38 The newer antiaddiction drug rimonabant has been shown to double the odds of quitting compared with placebo, markedly reducing postcessation weight gain at 10 weeks with few side effects, but has not yet been approved by the FDA.39

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CONCLUSION

Because education about the dangers of smoking increases the likelihood of quitting, health professionals must take an active role in providing this information for patients.40 A British study divided women smokers with abnormal Pap findings into groups that received different amounts of information about the connection between cervical cancer and smoking. The women who received information about smoking and cervical cancer were more likely to quit than the women who did not receive this information.7 Thus, by providing patients with the tools to make healthy decisions, physicians can reduce the death toll of smoking and improve the health of the nation.

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Kristen Ricchetti, is programs department intern; Eileen Resnick, PhD, is science programs manager; Viviana Simon, PhD, is director, scientific programs; and Jennifer Wider, MD, is a writing consultant. All are at the Society for WomenÍs Health Research, Washington, DC.

References

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