An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures.Abstract: Workplace exposures account for 5 to 25% of all bladder cancer bladder cancer Malignant tumour of the bladder. The most significant risk factor associated with bladder cancer is smoking. Exposure to chemicals called arylamines, which are used in the leather, rubber, printing, and textiles industries, is another risk factor. cases. A critical review of the literature between 1938 and 2004 was performed, with a focus on occupational exposures. Occupational exposure to bladder carcinogens Carcinogens Substances in the environment that cause cancer, presumably by inducing mutations, with prolonged exposure. Mentioned in: Colon Cancer, Rectal Cancer , particularly to [beta]-naphthylamine occur in a number of industries, including aromatic amine An aromatic amine is an amine with an aromatic substituent - that is -NH2, -NH- or nitrogen group(s) attached to an aromatic hydrocarbon, whose structure usually contains one or more benzene rings. Aniline is an example. manufacture, rubber and cable manufacture, and dyestuff manufacture and use. Risks to workers in a number of new occupations and industries are reviewed. Nonoccupational risk factors that are known or at one time have been thought to increase the risk of bladder cancer are also discussed. Key Words: occupational bladder, cancer, [beta]-naphthylamine, risk factors, occupational disease, occupational epidemiology ********** Bladder cancer is the most common cancer of the urinary system, and is ranked the eleventh most common cancer in the world. (1) In the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. , however, bladder cancer is the fourth most common cancer in males and the eighth in females. (2) Occupational exposure to bladder carcinogens, particularly to [beta]-naphthylamine, occur in a number of industries, including aromatic amine manufacture, rubber and cable manufacture, and dyestuff manufacture and use. Because occupational exposures may contribute to a risk of bladder cancer, a critical review of the literature between 1938 and 2004 was performed, with a focus on occupational exposures. Risks to workers in a number of new occupations and industries are also reviewed. In addition, nonoccupational risk factors that are known or at one time have been thought to increase the risk of bladder cancer are also discussed. Approximately 75% of newly diagnosed cases are superficial (3) and when first inspected, the majority of bladder cancer cases are inaccurately determined to be benign. (4) The natural history of bladder cancer is generally characterized by a short preclinical phase Noun 1. preclinical phase - a laboratory test of a new drug or a new invasive medical device on animal subjects; conducted to gather evidence justifying a clinical trial preclinical test, preclinical trial , which is suggested by the fact that bladder cancer is rarely an incidental finding at autopsy. (5) Between 80% and 95% of bladder cancer cases in the United States are transitional cell carcinomas tran·si·tion·al cell carcinoma n. A malignant neoplasm derived from transitional epithelium and occurring primarily in the urinary bladder, ureters, or renal pelvises. transitional cell carcinoma Bladder cancer, see there . (1,3,4,6-10) However, Matanoski and Elliott (6) reported a significantly greater proportion of squamous cell carcinomas squamous cell carcinoma n. A carcinoma that arises from squamous epithelium and is the most common form of skin cancer. Also called cancroid, epidermoid carcinoma. among blacks than whites (12% versus 2%), and among females than males (18.3% versus 7.6%). Similarly, Negri and La Vecchia La Vecchia is an Italian surname:
This page or section lists people with the surname La Vecchia. (10) reported 93% transitional cell carcinomas among whites, 85% among blacks, and a much lower proportion among Egyptians, where infection with Schistosoma hematobium is more common. Nonoccupational Risk Factors for Bladder Cancer Besides occupation, there are a number of nonoccupational factors that are known, or at one point have been thought, to increase the risk of bladder cancer. Smoking is the most well known of these factors, but others are discussed as well. Smoking Exposure to tobacco smoke has been well recognized as a bladder carcinogen carcinogen: see cancer. carcinogen Agent that can cause cancer. Exposure to one or more carcinogens, including certain chemicals, radiation, and certain viruses, can initiate cancer under conditions not completely understood. for decades. (4,11) Persons who smoke are estimated to have between two and four times greater risk of bladder cancer than persons who do not smoke. (1,3,4,6,10) Cordier et al (12) reported that the relative risk for bladder cancer appeared to vary "according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. dose, duration, time since cessation, [and] type of tobacco smoked." A number of other investigators have reported a dose relationship between increasing number of cigarettes smoked per day and increasing risk of bladder cancer. (1,10) However, Brennan et al (9) reported a threshold between 15 and 20 cigarettes per day, and suggested that duration is the principal determinant in bladder cancer risk with respect to smoking; this has been supported by other research. (3) Brennan et al (9) reported 100% increments of increased risk of bladder cancer for every ten years of smoking; from 100% increased risk after 20 years of smoking, to 500% increased risk after 60 years of smoking. Ma-tanoski and Elliott (6) reported that cessation must occur for 7 to 15 years before the risk of bladder cancer is reduced. Although cessation of smoking appears to reduce the risk of bladder cancer, it seems that the risk does not reduce to background levels. (1,3,9) However, it is important to note that Brennan et al (9) observed a decreased risk of bladder cancer among men who had stopped smoking for one to four years. Pelucchi et al (13) reported an increased risk of bladder cancer among smokers who used cigarettes with a high tar yield, but Yu et al (1) found no differences in risk between types of cigarette smoked. Other types of tobacco products have not yet been linked with risk of bladder cancer. (6) The risk of bladder cancer among smokers also appears to be modified by sex. Investigators have estimated that nearly half of bladder cancer cases are attributable to smoking among men; while approximately one-third of the cases among women are attributable to smoking. (3,10) In 2002, Yu et al (1) published a matched case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. of incident bladder cancer cases in Los Angeles Los Angeles (lôs ăn`jələs, lŏs, ăn`jəlēz'), city (1990 pop. 3,485,398), seat of Los Angeles co., S Calif.; inc. 1850. . Cases were matched to controls for age, sex, race and neighborhood. Female smokers were shown to have greater risk for bladder cancer than male smokers, even after adjusting for dose and duration of smoking. These results have been supported by other investigators, (11,13) who also suggest that "women may have a higher propensity for arylamine activation compared with men." (1) Sex In general, men have a significantly higher risk of bladder cancer than women (4,6); this increased risk may range between three- and five-fold. (1,3,10,14) This is especially true for industrialized in·dus·tri·al·ize v. in·dus·tri·al·ized, in·dus·tri·al·iz·ing, in·dus·tri·al·iz·es v.tr. 1. To develop industry in (a country or society, for example). 2. countries, which may suggest an occupational origin. (4,10,14) However, some investigators have reported a higher incidence of bladder cancer among men, even after adjustments for occupation and smoking have been made. (3,10) Race In addition to sex, race may also affect risk of bladder cancer. There are relatively few studies that examine bladder cancer mortality among racial minority groups in the United States; but in general, there appears to be a marked difference in incidence rates between races. (1,15) Matanoski and Elliott (6) suggest that the sex differences in bladder cancer risk are greater for whites than for nonwhites. In 2002, age-adjusted bladder cancer incidence among white males was 39 per 100,000. Among blacks, Asians, and Hispanics, the incidence was 17.7, 15.4, and 19.9 per 100,000, respectively. Incidence rates among females were substantially lower but followed a similar pattern. These rates must be interpreted with caution, however, since Hispanic origin and other race categories are not mutually exclusive Adj. 1. mutually exclusive - unable to be both true at the same time contradictory incompatible - not compatible; "incompatible personalities"; "incompatible colors" . (16) Although bladder cancer incidence in the general population is highest among whites, Schultz and Loomis (15) have suggested that historical job discrimination, where minorities are given the jobs with the highest exposure to carcinogenic carcinogenic having a capacity for carcinogenesis. agents, may result in higher incidence among minority populations in some occupations. Age Yu et al (1) estimated that two-thirds of bladder cancer cases occur in persons over the age of 65 years. A three-fold increased risk of bladder cancer among persons over the age of 70 years, compared with persons between the ages of 55 and 69 years, was reported by Pashos et al (3); the risk was even greater when compared with persons between 30 and 54 years of age. Other investigators have reported similar results. (6,8,17) Genetics Besides sex, race and age, other genetic factors may affect one's risk of bladder cancer. Molecular epidemiologists have implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. N-acetyltransferase (NAT (Network Address Translation) An IETF standard that allows an organization to present itself to the Internet with far fewer IP addresses than there are nodes on its internal network. 2) polymorphisms in the pathogenesis pathogenesis /patho·gen·e·sis/ (path?ah-jen´e-sis) the development of morbid conditions or of disease; more specifically the cellular events and reactions and other pathologic mechanisms occurring in the development of disease. of bladder cancer, believing NAT2 to deactivate de·ac·ti·vate tr.v. de·ac·ti·vat·ed, de·ac·ti·vat·ing, de·ac·ti·vates 1. To render inactive or ineffective. 2. To inhibit, block, or disrupt the action of (an enzyme or other biological agent). 3. carcinogenic aromatic amines. (18,19) Between 50% and 60% of Caucasians are 'slow' acetylators, (19-21) while Bi et al (20) reported a 'slow' acetylator prevalence of 10 to 30% among Asians from China and Japan. Studies in North America North America, third largest continent (1990 est. pop. 365,000,000), c.9,400,000 sq mi (24,346,000 sq km), the northern of the two continents of the Western Hemisphere. have generally found a high proportion of slow acetylators among persons occupationally exposed to aromatic amines. (18) Persons with the NAT2 'slow' acetylator phenotype phenotype (fē`nətīp'): see genetics. phenotype All the observable characteristics of an organism, such as shape, size, colour, and behaviour, that result from the interaction of its genotype (total genetic makeup) with have an approximately 1.3 to 1.5-fold increased risk of bladder cancer than 'rapid' acetylators. (1,19) Family History of Bladder Cancer A family history of bladder cancer may also increase one's risk of bladder cancer. Negri and La Vecchia (10) reported a 200% increased risk of bladder cancer among first-degree relatives of bladder cancer patients. Others have found similar results. (22,23) Urinary Tract Diseases A history of urinary tract diseases may also be a risk factor for bladder cancer. The parasite parasite, plant or animal that at some stage of its existence obtains its nourishment from another living organism called the host. Parasites may or may not harm the host, but they never benefit it. Schistosoma hematobium is believed to be a causative caus·a·tive adj. 1. Functioning as an agent or cause. 2. Expressing causation. Used of a verb or verbal affix. caus agent of bladder cancer, causing chronic inflammation chronic inflammation n. Inflammation that may have a rapid or slow onset but is characterized primarily by its persistence and lack of clear resolution; it occurs when the tissues are unable to overcome the effects of the injuring agent. of the bladder epithelium. A large proportion of bladder cancer cases are reported in areas with a high prevalence of Schistosoma hematobium, including Egypt and Zambia. Bladder cancer cases in these developing countries tend to be squamous cell carcinomas rather than transitional cell carcinomas. (3,4,6,10) Other urinary tract infections urinary tract infection (UTI), n infection in one or more of the structures that make up the urinary system. Occurs more often in women and is most commonly caused by bacteria. , urinary tract stones, and kidney stones Kidney Stones Definition Kidney stones are solid accumulations of material that form in the tubal system of the kidney. Kidney stones cause problems when they block the flow of urine through or out of the kidney. may slightly elevate the risk of bladder cancer. (10) Diet Besides genetic risk factors, environmental factors such as diet, fluid intake, drug intake, consumption of artificial sweeteners artificial sweetener: see sweetener, artificial. , place of residence, and exposure to hair dye may affect one's risk of bladder cancer. The majority of studies that have examined intake of fruit and vegetables have found that high consumption of these foods may decrease the risk of bladder cancer. (3,10,13) Other studies have not been consistent in reporting the potentially protective effects of vitamin A vitamin A also called retinol Fat-soluble alcohol, most abundant in fatty fish and especially in fish-liver oils. It is not found in plants, but many vegetables and fruits contain beta-carotene (see , carotenoids Carotenoids Carotenoids are yellow to deep-red pigments. Mentioned in: Vitamin A Deficiency carotenoids (k , and vitamin C vitamin C or ascorbic acid Water-soluble organic compound important in animal metabolism. Most animals produce it in their bodies, but humans, other primates, and guinea pigs need it in the diet to prevent scurvy. (3,10); and the harmful effects of increased fat intake. (3,10,13) The data examining these associations are limited. (10) Fluid Intake Increased fluid intake may reduce the risk of bladder cancer because it increases the frequency of urination urination Process of excreting urine from the bladder (see urinary system). Nerve centres in the spinal cord, brain stem, and cerebral cortex control it through involuntary and voluntary muscles. The need to void is felt when the bladder holds 3. , which limits the duration of contact between carcinogens and the bladder epithelium. (10,24) Type of fluid may also play a role in the risk of bladder cancer; a number of studies have suggested that coffee drinking may elevate the risk for bladder cancer, though trends of duration or dose have not been observed. (4,6,10,13,25) Negri and La Vecchia (10) also suggested that the association between coffee intake and risk of bladder cancer may be confounded by smoking. Drugs Risk of bladder cancer has been associated with heavy consumption of phenacetin-containing analgesics Analgesics Definition Analgesics are medicines that relieve pain. Purpose Analgesics are those drugs that mainly provide pain relief. . (6,10) Phenacetin phenacetin /phe·nac·e·tin/ (fe-nas´e-tin) an analgesic and antipyretic, whose major metabolite is acetaminophen, now little used because of its toxicity. phenacetin see acetophenetidin. may be linked to bladder cancer because it is a derivative of aniline aniline (ăn`əlĭn), C6H5NH2, colorless, oily, basic liquid organic compound; chemically, a primary aromatic amine whose molecule is formed by replacing one hydrogen atom of a benzene molecule with an amino . (6) Artificial Sweeteners Since the late 1970s, the role of artificial sweeteners such as saccharin saccharin (săk`ərĭn), C7H5NSO3, white, crystalline, aromatic compound. It was discovered accidentally by I. Remsen and C. Fahlberg in 1879. Pure saccharin tastes several hundred times as sweet as sugar. in bladder cancer risk has been questioned. (3,10) Hoover and Strasser (26) conducted one of the largest studies of this association, based on 3,010 bladder cancer cases and 5,783 controls drawn from the US population. No significant findings were reported. Place of Residence Marsh and Cassidy (8) and Matanoski and Elliott (6) reported that the risk of bladder cancer is elevated in densely populated pop·u·late tr.v. pop·u·lat·ed, pop·u·lat·ing, pop·u·lates 1. To supply with inhabitants, as by colonization; people. 2. industrial areas and in urban areas, respectively. Possible explanations include: industries where occupational exposure to carcinogens may occur are likely to concentrate in densely populated or urban areas; persons living in densely populated areas are perhaps exposed to more vehicle emissions than in rural areas; and there may be other lifestyle factors that are more prevalent in urban areas, which are also risk factors for bladder cancer. Exposure to Hair Dye Gago-Dominquez et al (27) reported a statistically significant association between both frequency of use and duration of exposure to permanent hair dye and increased risk of bladder cancer. Both Gago-Dominquez et al (27) and Pashos et al (3) reported that women who use permanent hair dyes at least once per month had twice the risk of bladder cancer than women who did not use permanent hair dyes. Occupational exposure to hair dye has been shown to increase bladder cancer risk, primarily among hairdressers and possibly barbers, as mentioned below. Nonoccupational Risks Summarized There are a number of nonoccupational risk factors for bladder cancer including smoking history, genetics, sex, race, age, fluid intake, diet, drug intake, history of urinary tract diseases, place of residence, exposure to hair dye, and family history of bladder cancer. After smoking, occupation is the second greatest risk factor for bladder cancer. (27,28) Occupational Risk Factors for Bladder Cancer by Industry Some studies have shown that occupational exposures may be responsible for nearly one-quarter of bladder cancer cases. (19,28-30) However, most studies suggest a lower proportion of bladder cancer related to occupation exposures, with estimates of 10% among men and 5% among women. (31,32) Aromatic amines especially appear to be specific to the urinary bladder urinary bladder n. A musculomembranous elastic receptacle in the anterior part of the pelvic cavity serving as the temporary storage place for urine. ; and are currently the only agents whose association with bladder cancer has been clearly defined. (17,19,20,28,33) In 1895, a German surgeon named Rehn was the first to point to the increased number of bladder cancer cases among magenta manufacturers. Although he blamed the wrong exposure (aniline), attention was focused on the increased number of bladder cancer cases. (4,25,34-40) It was not until 1954 when Case et al (35) reported a study of British chemical workers, that [beta]-naphthylamine (BNA BNA Bureau of National Affairs, Inc. BNA Birds of North America BNA block numbering area (US Census) BNA British North America BNA Banco Nacional de Angola (National Bank of Angola) ) was demonstrated to be associated with a 200-fold increase in risk of bladder cancer. BNA, an aromatic amine resulting from the distillation distillation, process used to separate the substances composing a mixture. It involves a change of state, as of liquid to gas, and subsequent condensation. The process was probably first used in the production of intoxicating beverages. of coal and coal tar coal tar, product of the destructive distillation of bituminous coal. Coal tar can be distilled into many fractions to yield a number of useful organic products, including benzene, toluene, xylene, naphthalene, anthracene, and phenanthrene. , is now one of the best established carcinogens (39,41); it has been classified as a Group 1 carcinogen (carcinogenic to humans) by the International Agency for Research on Cancer The International Agency for Research on Cancer (IARC, or CIRC in its French acronym) is an intergovernmental agency forming part of the World Health Organisation of the United Nations. Its main offices are in Lyon, France. (IARC). (19,42) BNA has been gradually substituted by phenyl-[beta]-naphthylamine (PBNA), which has also been shown to partially metabolize me·tab·o·lize v. 1. To subject to metabolism. 2. To produce by metabolism. 3. To undergo change by metabolism. metabolize to subject to or be transformed by metabolism. in the body to BNA. (7,18,41) BNA has also been shown to be a contaminant contaminant /con·tam·i·nant/ (kon-tam´in-int) something that causes contamination. contaminant something that causes contamination. in other chemicals and industries. (37) Because of the carcinogenicity carcinogenicity /car·ci·no·ge·nic·i·ty/ (kahr?si-no-je-nis´i-te) the ability or tendency to produce cancer. carcinogenicity the ability or tendency to produce cancer. of BNA, a number of regulatory agencies regulatory agency Independent government commission charged by the legislature with setting and enforcing standards for specific industries in the private sector. The concept was invented by the U.S. have banned the use and manufacture of BNA--Switzerland in 1938, Great Britain Great Britain, officially United Kingdom of Great Britain and Northern Ireland, constitutional monarchy (2005 est. pop. 60,441,000), 94,226 sq mi (244,044 sq km), on the British Isles, off W Europe. The country is often referred to simply as Britain. in 1952, and Italy in 1960. (38) In the United States, BNA was not banned, but OSHA OSHA n. Occupational Safety and Health Administration, a branch of the US Department of Labor responsible for establishing and enforcing safety and health standards in the workplace. claimed that strict control of its use has had a similar effect. (39) Miyakawa et al (17) also report a decreasing incidence of bladder cancer in Japan since 1972, when the production and use of dyestuffs dyestuffs npl → colorants mpl dyestuffs dye npl → Farbstoffe pl dyestuffs npl → coloranti containing BNA were legally prohibited. The carcinogenicity of BNA has also been well established in dogs, monkeys and hamsters. (25,38,44-46) Besides aromatic amines, other agents such as paints, dyes, metals, industrial oils/cutting fluids and polycyclic aromatic hydrocarbons polycyclic aromatic hydrocarbon n. Any of a class of carcinogenic organic molecules that consist of three or more rings containing carbon and hydrogen and that are commonly produced by fossil fuel combustion. (PAHs), have also been linked to increased risk of bladder cancer. (14,28) Processes involving incomplete combustion pyrolysis py·rol·y·sis n. Decomposition or transformation of a chemical compound caused by heat. pyrolysis (pīrol´isis), n or pyrosynthesis of organic matter result in the production of PAHs. Thus, exposure to PAHs may occur in a variety of occupations, including gas workers, roofers, chimney sweeps chimney sweep n. A worker employed to clean soot from chimneys. Also called chimney sweeper. chimney sweep Noun a person who cleans soot from chimneys chimney sweep , aluminum smelter workers, coal miners, blacksmiths, truck drivers or individuals exposed to exhaust fumes exhaust fumes fumes given off by vehicles; contain some carbon monoxide, the amount varying with the efficiency of combustion in the particular engine. In most engines the use of exhaust fumes for euthanasia is not recommended because it operates partly on the carbon dioxide , glass processors, brickyard workers, tar and asphalt asphalt (ăs`fôlt, –fălt), brownish-black substance used commonly in road making, roofing, and waterproofing. Chemically, it is a natural mixture of hydrocarbons. workers. (47) Clavel et al (47) reported an increased risk of bladder cancer among workers exposed to PAHs, but cited concomitant exposure to aromatic amines generated during the same pyrolysis as a confounding confounding when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies. confounding factor factor. Most occupational exposures to the agents mentioned above occur among workers employed in aromatic amine manufacture, dyestuff manufacture and use, rubber and cable manufacture, textile and leather works, driving occupations, and the coal tar, aluminum, and gas industries. (3,4,8,10,12,14,19,27,30,48) However, the first cases of occupational bladder cancer were found in workers in the rubber tire and textile dye industries. (1) Aromatic Amine Manufacture Stern et al (38) conducted a cohort study A cohort study is a form of longitudinal study used in medicine and social science. It is one type of study design. In medicine, it is usually undertaken to obtain evidence to try to refute the existence of a suspected association between cause and disease; failure to refute of 1,312 male workers employed for at least one day between 1940 and 1973 at the last facility in the United States producing BNA. The investigators reported a nonsignificant non·sig·nif·i·cant adj. 1. Not significant. 2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence. standardized mortality ratio The standardized mortality ratio or SMR in epidemiology is the ratio of observed deaths to expected deaths according to a specific health outcome in a population and serves as an indirect means of adjusting a rate. (SMR (Specialized Mobile Radio) The communications services used by police, ambulances, taxicabs, trucks and other delivery vehicles. Throughout the U.S., approximately 3,000 independent operators are licensed by the FCC to offer this service, which provides always-on ) of 286 based on two observed bladder cancer deaths (95% CI = 35-1032). A limiting factor A factor or condition that, either temporarily or permanently, impedes mission accomplishment. Illustrative examples are transportation network deficiencies, lack of in-place facilities, malpositioned forces or materiel, extreme climatic conditions, distance, transit or overflight rights, of their study was the small percentage of the cohort (15%) being exposed to BNA. Cassidy et al (11) conducted a mortality study of 374 male and 26 female workers with probable past exposure to BNA at a chemical plant in Pennsylvania between 1940 and 1981. BNA was manufactured at this plant until 1962, when it was banned in that state. Although they had a small number of bladder cancer cases in their cohort, the SMR for bladder cancer was elevated (SMR = 16.8, 95% CI = 4.6-43.1), and was associated with subjects at risk before age 45, hired before cessation of BNA manufacture (ie, 1963), employed for at least five years, followed for 20 to 29 years since first employment, and employed in the highest BNA exposure risk group. In addition, the investigators reported increased mortality risk for each cancer site and for all cancers combined. Dyestuff Manufacture and Use A case-control study was conducted by Coggon et al (49) to investigate bladder cancer mortality in a variety of occupations. They examined 291 patients less than 50 years of age who died as a result of bladder cancer in England or Wales Wales, Welsh Cymru, western peninsula and political division (principality) of Great Britain (1991 pop. 2,798,200), 8,016 sq mi (20,761 sq km), west of England; politically united with England since 1536. The capital is Cardiff. between 1975 and 1979. Two controls, deceased from other causes, were matched to each case by sex, year of birth and death, and geographic region. The investigators reported a relative risk of 5.0 (95% CI = 1.0-25.8) among workers employed in jobs with high exposure to printing inks. Schoenberg et al (30) also conducted a case-control study of occupational bladder cancer risk. The investigators examined 658 bladder cancer cases and 1,258 controls among white males in New Jersey. Cases were patients newly diagnosed with bladder cancer between 1978 and 1979; controls were recruited via random digit dialing Random digit dialing (RDD) is a method for selecting people for involvement in telephone statistical surveys by generating telephone numbers at random. Random digit dialing has the advantage that it includes unlisted numbers that would be missed if the numbers were selected from a and Medicare. An increased risk of bladder cancer among workers exposed to paint (OR = 1.56; 95% CI = 1.15-2.12) and printing ink (OR = 1.59; 95% CI = 2.47) was seen. Bi et al (20) conducted a mortality study of 1,972 workers employed in benzidine-exposed jobs in the Shanghai and China dyestuff industries between 1945 and 1977. A comparison group of 1,974 unexposed workers was used for some of the analyses. The investigators reported a 17-fold risk for bladder cancer mortality and a 25-fold risk for bladder cancer incidence among the benzidine-exposed workers. Naito et al (50) reported a cohort study of 442 workers (437 men and 5 women) employed at a dyestuff factory in Japan between 1935 and 1988. The workers had been part of a cancer screening program at the factory. Workers were exposed to a variety of chemicals, including BNA, benzidine benzidine /ben·zi·dine/ (ben´zi-den) a carcinogen and toxin once widely used as a test for occult blood. ben·zi·dine n. , [alpha]-naphthylamine, and Dianisidine. The investigators reported an increased mortality among workers engaged in benzidine manufacture (SMR = 63.6; 95% CI = 30.5-117.0), benzidine use (SMR = 27.0; 95% CI = 8.8-63.0) and BNA manufacture (SMR = 48.4; 95% CI = 10.0-141.5). There was no increased risk for workers exposed to [alpha]-naphthylamine. Bulbulyan et al (34) conducted a study of 4,581 men and women working at an aniline dye Noun 1. aniline dye - any of many dyes made from aniline dye, dyestuff - a usually soluble substance for staining or coloring e.g. fabrics or hair production facility in Moscow in 1975. Of these workers, 514 (21%) men and 287 (13%) women were exposed to [beta]-naphthylamine or benzidine. The investigators reported an increased mortality and incidence for all cancers combined and for bladder cancer, specifically. Men had an SMR of 279 (95% CI = 192-391), while women had a slightly higher SMR of 311 (95% CI = 149-571). The investigators also reported an increased risk of bladder cancer with both decreased age at diagnosis and decreased age at hire. Although the facility produced BNA until 1951, workers hired after 1951 also showed a greater risk of bladder cancer than the general population, although this risk was not as great as for those hired before 1951 during BNA production. An increased risk of bladder cancer was also reported by Axtell et al, (41) who investigated bladder cancer incidence and mortality among 1,314 male employees of a synthetic dye synthetic dye n. Any of the organic dyes originally derived from coal-tar derivatives, but currently synthesized from benzene and its derivatives. plant in the United States that manufactured BNA between 1940 and 1979. The SMR for bladder cancer was 2.4 (95% CI = 0.5-0.7), and increased to 5.6 (95% CI = 2.4-11.1) when multiple causes of death were considered. In addition, using multiple causes of death, the SMR for workers employed less than one year and greater than ten years was 3.7 (95% CI = 1.21, 8.68) and 39.8 (95% CI = 8.20, 116.25), respectively. Rubber and Cable Manufacture Fox and Collier (36) reported a survey of occupational cancer among 40,867 men employed for at least one year in the rubber and cable making industries in the United Kingdom in 1967. The investigators expected 19 bladder cancers, but observed 37, which was highly statistically significant (P < 0.001). In the tire sector specifically, the investigators reported an SMR of 183 (P < 0.05). Monson and Fine (43) conducted a mortality and morbidity study of 13,570 white male workers employed for at least five years in the rubber industry in Ohio between 1940 and 1976. The investigators reported the greatest excess cases of bladder cancer among workers who were ever employed in the chemical plant (SMR = 1.67) and who were employed at least five years in the tire building (SMR = 1.32). Excess bladder cancer was limited to those who had worked at least 15 years in that particular department. Checkoway et al (7) reported a case-control study of 220 male employees from five rubber and tire manufacturing facilities in Ohio. Cases were identified from hospital records and death certificates. Two industry controls were matched to each case by sex, race, year of birth, and company. The investigators found a positive trend for bladder cancer with increasing duration of exposure among workers with jobs early in the tire manufacturing process--these jobs had greater exposure to volatized rubber chemicals. Sorohan et al (51) conducted a cohort study of 2,160 male production workers who had been employed at least six months at a plant that produced chemicals for the rubber industry in Wales between 1955 and 1984. The investigators reported a statistically significant excess of bladder cancer mortality among workers potentially exposed to one or more of the chemicals investigated (aniline, o-toluidine, 2-mercap-tobenzothiazole, and phenyl-[beta]-naphthylamine), compared with the general population of England Due to the lack of authoritative contemporary sources, estimates of the population of England for dates prior to the first census in 1801 vary considerably. It has been suggested that even the 1801 census may have left up to 250,000 people uncounted. and Wales. The SMR was 277 (95% CI = 127-526), but the excess was seen mainly among workers who began employment before 1955 and worked for at least 20 years (SMR = 560; 95% CI = 225-1154). Veys (52) reported a study of 2,090 male rubber industry workers employed in Britain before the removal of BNA from the processes (before 1950) and 3,038 workers employed in the same industry after the removal of BNA (after 1950). Workers employed while BNA was still in use were shown to have 2.8 times greater risk of bladder cancer than workers who were employed after 1950 (95% CI = 1.8-4.4). Coggon et al (48) also reported an increased risk of bladder cancer among 291 rubber workers in their case-control study of bladder cancer mortality in an array of occupations. Due to small numbers, however, their findings were not statistically significant. Diesel Exhaust Exposure Boffetta and Silverman (53) conducted a meta-analysis of 35 studies examining the association between occupational exposure to diesel exhaust and bladder cancer. Drivers of trucks and buses had summary relative risks of bladder cancer of 1.17 (95% CI = 1.06-1.29) and 1.33 (95% CI = 1.22-1.45), respectively. Workers with high exposure to diesel exhaust had more than 1.4 times increased risk of bladder cancer (95% CI = 1.18-1.76). In the case-control study conducted by Schoenberg et al, (30) investigators reported an increased risk of bladder cancer among gas station workers (OR = 2.35; 95% CI = 1.47-3.78). Baxter and McDowall (54) also reported an increased risk of bladder cancer mortality among road transport drivers (RR = 1.7; P < 0.05). Silverman et al (55) reported an overall relative risk of lower urinary tract cancer of 2.1 (95% CI = 1.4-4.4) among truck drivers, with an increasing risk with longer duration of employment; and a relative risk of nearly 12 (95% CI = 2.3-61.1) for drivers exposed to diesel exhaust. Hairdressers The IARC classifies occupation as a hairdresser or barber in Group 2A (probable carcinogen). (18,19) Gago-Domin-quez et al (27) estimated that approximately two million professional hairdressers, barbers and beauticians work in North America and Europe. These workers would likely be exposed to large amounts of aromatic amine-containing hair dyes on a regular basis. The investigators conducted a population-based case-control study of 1,514 incident cases of bladder cancer in Los Angeles, CA, and reported that subjects who worked as hairdressers for at least 10 years had a five-fold increased risk of bladder cancer than subjects not occupationally exposed to hair dyes. Kogevinas et al (28) combined data from 11 European case-control studies, including 3,346 cases and 6,840 controls. They reported an increased risk of bladder cancer among hairdressers, though the increase was not statistically significant (OR = 1.6, 95% CI = 0.8-2.5). Occupational Exposures Summarized There are a number of industries and occupational exposures that have been shown to increase one's risk of bladder cancer. Persons employed in the aromatic amine manufacturing industry, dyestuff manufacture and use, rubber and cable manufacture, driving industries, and hairdressing hairdressing, arranging of the hair for decorative, ceremonial, or symbolic reasons. Primitive men plastered their hair with clay and tied trophies and badges into it to represent their feats and qualities. , have shown elevated incidence of bladder cancer. Latency The latent period latent period n. 1. The period elapsing between the application of a stimulus and the obvious response, such as the contraction of a muscle. 2. of bladder cancer is generally very long, but has been shown to vary considerably; as short as 16 years and as long as 45 years. (6,8,35,44,52,56) Because BNA is an occupational carcinogen with a long minimum latency, it is not likely to have an observable effect until persons are between the ages of 60 and 80 years. (6,17,49) Miyakawa et al (17) evaluated the latent period of bladder cancer among 236 workers employed in Japanese dyestuff plants between 1962 and 1996. Of the 19 cases of bladder cancer reported in this cohort, the mean latent period was 29.5 years from onset of exposure and 20 years from final exposure to tumor development tumor development A multistep process that occurs over yrs in which a tissue accumulates genetic hits that eventually translate into a neoplasm with metastatic potential. See One-hit, two-hit model. . The duration of exposure for these workers varied between 11 months and 16 years, with a mean of seven years. Marsh and Cassidy (8) discussed results from the Drake Health Registry Study, which is an ongoing bladder cancer screening program for workers with potential exposure to BNA. Two of their bladder cancer cases had durations of exposure between two and four months. One of these cases was described as a 'light' smoker smoker A person who smokes tobacco, almost always understood to be cigarettes Ratio of ♂:♀ smokers Philippines64/19, China61/7, Saudi Arabia53/2, Russia50/12 , while the other was a nonsmoker. Other investigators have reported bladder cancer among workers with a duration of exposure less than one year. (38) Cassidy et al (11) reported that workers employed for five years or longer had the highest standardized mortality ratios for bladder cancer. In general, it appears that increasing duration of exposure results in an increased risk of bladder cancer. (43,48) Future Research Bladder cancer has been studied in a number of industrial settings, primarily in rubber and dyestuff manufacture and use. (1,7,13,41,49) The chemical and, more recently, the plastics industries have been examined in general, but these sectors include a broad array of processes and products. (57) There are a number of other issues that complicate the epidemiologic research of occupational bladder cancer. First, there is often a lack of adequate smoking history data for cohort members. Since smoking is the main risk factor for bladder cancer, inclusion of smoking data could help investigators separate bladder cancers due to smoking from those due to occupational exposures. Second, information on other nonoccupational risk factors, such as diet and family history of bladder cancer, are also lacking. These issues are further complicated by a lack of industrial hygiene data. In addition, better characterization of the risk associated with different racial and ethnic groups is warranted. Historical job discrimination may result in higher rates of bladder cancer among minorities in higher risk occupations. However, since there are few studies that examine bladder cancer mortality among racial minority groups and the CDC's National Program of Cancer Registries A cancer registry is a systematic collection of data about cancer and tumor diseases. The data is collected by Cancer Registrars. Cancer Registrars capture a complete summary of patient history, diagnosis, treatment, and status for every cancer patient in the United States, and does not distinguish between Hispanic whites and non-Hispanic whites, determining differential risk is problematic. (16) A new at-risk group are workers employed in the plastics industry, who may be exposed to a variety of substances, such as organic solvents, monomers and polymers. In selected plastics manufacturing sectors (eg, polyethylene pipe), opportunities for potential exposure to establish bladder carcinogens have been described, but details regarding the greatest at-risk worker groups are lacking. (58) This makes it difficult to distinguish the specific exposure(s) causing bladder cancer. In addition, workers in the plastics industries are often combined into cohorts with workers from other industries, such as rubber products (59) or metal processing, (60) which further increases the difficulty in indicating which industrial exposure(s) causes disease. Felknor et al (61) reported the methodology of a bladder cancer screening program for workers with potential exposure to BNA in the polyethylene pipe manufacturing industry; mortality data from that study are being analyzed. Cowles et al (62) reported a mortality study among workers at a plastics and resins research and development facility, who were exposed to polyethylene, polypropylene polypropylene (pŏl'ēprō`pəlēn), plastic noted for its light weight, being less dense than water; it is a polymer of propylene. It resists moisture, oils, and solvents. , and epoxy resins epoxy resins, group of synthetic resins used to make plastics and adhesives. These materials are noted for their versatility, but their relatively high cost has limited their use. . These investigators did not examine bladder cancer specifically, but reported a statistically significant increased risk of pancreatic cancer pancreatic cancer Malignant tumour of the pancreas. Risk factors include smoking, a diet high in fat, exposure to certain industrial products, and diseases such as diabetes and chronic pancreatitis. Pancreatic cancer is more common in men. . With over 800,000 persons employed in plastics materials (SIC 282) and miscellaneous plastics products (SIC 308) in the United States in 2001, (63) further investigation into the effects of occupational exposure to carcinogens in the plastics industry, and specifically among workers exposed to polyethylene, is warranted. References 1. 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Colt JS, Baris D, Stewart P, et al. Occupation and bladder cancer risk in a population-based case-control study in New Hampshire New Hampshire, one of the New England states of the NE United States. It is bordered by Massachusetts (S), Vermont, with the Connecticut R. forming the boundary (W), the Canadian province of Quebec (NW), and Maine and a short strip of the Atlantic Ocean (E). . Cancer Causes Control 2004;15:759-769. 61. Felknor SA, Delclos GL, Lerner SP, et al. Bladder cancer screening program for a petrochemical cohort with potential exposure to beta-napthylamine. J Occup Environ Med 2003;45:289-294. 62. Cowles SR, Tsai SP, Gilstrap EL, et al. Mortality among employees at a plastics and resins research and development facility. Occup Environ Med 1994;51:799-803. 63. United States Bureau of Labour Statistics. Available at: http://www.bls-.gov/oes/2001/oessrci.htm. Accessed June 29, 2005. Sandra M. Olfert, PhD, MSc, Sarah A. Felknor, DrPH, MS, and George L. Delclos, MD, MPH From the University of Texas Health Science Center at Houston, School of Public Health, Southwest Center for Occupational and Environmental Health, Houston, TX. Reprint reprint An individually bound copy of an article in a journal or science communication requests to Sarah A. Felknor, DrPH, MS, the University of Texas School of Public Health The Texas Legislature authorized the creation of a school of public health in 1947, but did not appropriate funds for the school until 1967. The first class was admitted in the Fall of 1969, doubled in the second year and doubled again in the third year, with continued grwoth over the at Houston, Southwest Center for Occupational and Environmental Health, PO Box 20186, Houston, TX 77030. Email: sarah.a.felknor@uth.tmc.edu Supported in part by Grant No. T42 OH008421 from the National Institute for Occupational Safety and Health National Institute for Occupational Safety and Health, n.pr an institute of the Centers for Disease Control and Prevention that is responsible for assuring safe and healthful working conditions and for developing standards of safety and health. . The funding agency had no involvement in the study design, data collection, data analysis, interpretation of data, writing of the paper and/or in the decision to submit the paper for publication. Accepted August 7, 2006. RELATED ARTICLE: Key Points * Workplace exposures account for 5 to 25% of all bladder cancer cases. * The epidemiological research of occupational bladder cancer is complicated by a number of issues, including lack of adequate smoking history, lack of information on other nonoccupational risk factors, and lack of industrial hygiene data. * In selected plastics manufacturing sectors, opportunities for potential exposure to establish bladder carcinogens have been described, but details regarding the greatest at-risk worker groups are lacking. * With over 800,000 persons employed in plastics materials and miscellaneous plastics products in the United States in 2001, further investigation into the effects of occupational exposure to carcinogens in the plastics industry is warranted. RELATED ARTICLE: Nonoccupational Risk Factors for Bladder Cancer 1. Smoking history 2. Male sex 3. Caucasian race Noun 1. Caucasian race - a light-skinned race Caucasoid race, White people, White race race - people who are believed to belong to the same genetic stock; "some biologists doubt that there are important genetic differences between races of human beings" 4. Increased age 5. Genetics 6. Family history 7. History of urinary tract diseases 8. Diet 9. Decreased fluid intake 10. Drugs 11. Geographic area 12. Exposure to hair dye |
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