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Declining Cancer Rates in the 1990s

From the Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, and American Cancer Society, National Home Office, Atlanta, GA.

Address reprint requests to Roberta McKean-Cowdin, MD, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, MS/44, Los Angeles, CA 90033-0800; email mckean{at}hsc.usc.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
PURPOSE: To provide evidence of a substantial decline in cancer rates for the period 1991 through 1995 and characterize major risk factors that seem to be driving secular trends in cancer mortality and incidence.

DESIGN: Incidence and mortality rates were calculated using national surveillance data collected through the Surveillance, Epidemiology, and End Results (SEER) program and the National Center for Health Statistics.

RESULTS: All-sites cancer incidence and mortality fell in the period 1991 through 1995; this decline is largely attributable to decreases in the smoking-related cancers, especially lung cancer. Of the 20 leading incident cancers today, both incidence and mortality are decreasing among 11 sites for men and 12 for women. In men, the decline in mortality has been notable and is especially apparent for the smoking-related cancers, including those of the lung, oral cavity and pharynx, larynx, and, to a lesser extent, bladder. In women, all-sites mortality decreased only approximately 0.4% from 1991 through 1995. Three cancers continued to show substantial increases in mortality through 1995 for both men and women (liver, multiple myeloma, and non-Hodgkin’s lymphoma), while incidence rates continued to climb for liver cancer, non-Hodgkin’s lymphoma, and melanoma.

CONCLUSION: Data from the SEER program on recent trends in cancer incidence and mortality show that cancer rates are generally on the decline, largely because of reductions in smoking-related cancers. A consistent increase in mortality rates due to liver cancer poses a new health care challenge, one that will require the development of an effective treatment for individuals currently infected with hepatitis C or B to prevent mortality rates from continuing to increase.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
NATIONAL SURVEILLANCE of cancer incidence, through the Surveillance, Epidemiology, and End Results (SEER) program,¹ and of cancer mortality, through the National Center for Health Statistics,² continues to provide a ready source of data on cancer trends in the United States. As we begin a new century, it seems propitious to reexamine these trends to establish what we have accomplished and to attempt to predict future trends and important issues in cancer incidence and mortality. The top 10 incident cancers projected for 1999 (Table 1)³ included largely the same sites as those projected in the late 1980s,⁴ but prostate and breast cancer have now replaced lung and colorectal cancer as the most frequently diagnosed cancers. Nonetheless, dramatic changes have occurred in the trends in mortality and incidence of many cancers; remarkably, incidence rates of cancer are now decreasing or have stabilized for all but three of the 20 most frequently diagnosed cancers in men and women (liver, non-Hodgkin’s lymphoma [NHL], and melanoma).

	CANCER TRENDS

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

In women, all-sites mortality decreased only approximately 0.4% from 1991 through 1995. Mortality and incidence rates for smoking-related cancers among women are also beginning to change, with dramatic decreases occurring among those under 65 years of age in incidence rates of lung (-7.5%), larynx (-14.9%), and, to a lesser degree, bladder (-1.6%) cancer. Mortality rates for cancer of the pancreas are relatively stable in women, even though incidence is decreasing (-4.3%) at a rate similar to that in men.

The four cancers that had shown major decreases in both mortality and incidence in the period 1973 through 1987 (stomach and Hodgkin’s disease for men and women; cervix and endometrium for women) continued to show decreases during the period 1991 through 1995, with the exception of cancers of the endometrium, which is stable. The decreases in cancers of the stomach, cervix, and endometrium remain illustrative of the potential impact of widely implemented cancer prevention programs or of the impact of treatment, as in the case of Hodgkin’s disease, on cancer mortality.⁴

Three cancers continued to show substantial increases in mortality through 1995 in men and women. Liver cancer showed the greatest increase in mortality and incidence among both men and women, increasing 12.3% in men and 12.9% in women during the 5-year period (Tables 2 and 3). The increase in liver cancer rates are likely to be due to increased infection rates with the hepatitis C virus (HCV) and hepatitis B virus (HBV), known hepatic carcinogens.⁶ Assuming this is the correct explanation, the long latency period between infection and cancer development indicates that mortality rates for this disease will continue to increase in the near future unless effective treatments are found. Mortality has also increased for multiple myeloma (5.6% in men and 3.8% in women), although it seems that incidence is declining. Mortality from NHL increased in both men and women by approximately 6%, and its incidence increased approximately 3%. The reason for the increases in rates for NHL during the past 20 years is unclear, although it seems that changes in diagnostic and classification practices may have contributed.

In the sections below, we review the current state of knowledge and characterize the major risk factors that seem to be driving secular trends in cancer mortality and incidence. We categorize these sites by common risk factors, including smoking, diet, hormones, and other factors unique to a specific cancer site. Among these categories, we explore the potential impact of primary prevention, early detection, and treatment advances on future mortality and incidence patterns. Furthermore, we discuss what we have learned from past efforts in prevention and treatment and discuss promising directions for etiologic and prevention research.

	TOBACCO USE AND SMOKING

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
Lung, Larynx, Oral Cavity and Pharynx, and Bladder
Cigarette smoking began to grow rapidly in popularity in the United States in the 1920s after World War I and continued to increase among white men until 1952, when the first scientific reports that linked cigarette smoking to lung cancer were published. Historically, the rates of smoking among men have been much higher than among women, but the difference by sex began to diminish as the rate among men declined and the rate among women rose. By 1993, the percentage of adult men and women who smoked was only moderately different (31.7% of men and 26.8% of women).⁷ The delayed health effects of smoking became very much apparent by the late 1940s, with rapidly rising rates of smoking-related cancer mortality and incidence in women and continuing rising rates in men.⁵

It now seems that smoking intervention and education programs have effectively reversed the upward trend in smoking-related cancer incidence that occurred unabated through 1990. Those cancers that are most clearly smoking-related, including cancers of the lung, larynx, oral cavity and pharynx, and bladder, all decreased dramatically in incidence in white men from 1991 through 1995 (Table 2). Rates for these sites also declined in white women, with the exception of lung cancer, which seems now to have stabilized in incidence (0.1% change from 1991 through 1995) (Table 3). African-American men and women generally experienced similar patterns, with a few exceptions: oral-cavity cancer continued to increase in men, as did larynx cancer in women. A thorough review of the effects of tobacco smoking on cancer incidence and mortality, specifically lung cancer, was published in 1999.⁸ Given the declining smoking rates in adult men and women in both racial/ethnic groups in the previous decades, rates for these cancers should continue to decline.

A key to maintaining the decreasing trend of smoking-related cancer incidence and deaths is the prevention of smoking in young people. Although the numbers of high school students that started smoking decreased from 1983 to 1993, there is evidence that the rate of smoking is on the increase again. In 1997, the national prevalence of current cigarette smoking among high school students was 32% higher than in 1991.⁹ Furthermore, the use of cigars and smokeless tobacco among teens is also on the increase, the latter with important future implications for cancer of the oral cavity.

Pancreatic Cancer
Experimental and epidemiologic^10-25 studies have shown that smoking is a risk factor for pancreatic cancer. Pancreatic cancer risk is twice as high among people who smoke and highest among people who smoke the greatest amounts. Furthermore, the risk rapidly decreases after smoking cessation. Nevertheless, it has been estimated that only 25% of pancreatic cancer is attributable to this behavior.²⁵ Pancreatic cancer rates fell from 1991 through 1995 among both men and women and in African-Americans and whites. It is likely that the fall in pancreatic mortality and incidence from 1991 through 1995 is at least partially attributable to the decrease in smoking rates. A possible explanation for this association is a smoking-induced elevation of levels of cholecystokinin, an enzyme that has been shown to be a promoter of pancreatic carcinogenesis in rats^26-29 and of human pancreatic cells in vitro.^30,31

	ULTRAVIOLET RADIATION

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
Melanoma
From 1973 through 1991, the incidence of malignant melanoma was increasing as rapidly as that of any single cancer site, with the exception of prostate cancer in men and lung cancer in women (Tables 2 and 3). Mortality also was rising, but at a much lower rate. From 1991 through 1995, the incidence of malignant melanoma continued to increase (7.6% in men and 3.8% in women) at a lower rate than it had from 1973 through 1991; however, mortality declined in both men and women (less than 1%).

The cause of malignant melanoma seems to include both an underlying genetic susceptibility and intermittent, intense exposure to ultraviolet radiation, especially in early childhood.^32,33 The reason for the dramatically rising rates of melanoma in the 1970s and 1980s is not known, but it may reflect a true increase in rates due to changing patterns of sun exposure or improvements in detection of melanoma because of growing awareness and screening efforts. The discrepancy between changes in incidence and mortality rates seems to support a role for improved detection of the earlier-stage, thinner lesions typically associated with better survival.^34,35

Early detection and surgical treatment of melanoma can result in 90% disease-free survival over 10 years; however, for those cases not successfully treated by surgery alone, chemotherapy offers little additional benefit.³⁶ A combination of surgery and immunotherapy does seem to prolong survival time but does not currently eliminate the disease.³⁶

	DIET

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
Stomach and Colorectal Cancers
Evidence supporting an association between diet and cancer has been sought for many cancers, especially for cancers of the colorectum, stomach, prostate, and breast, but has been most convincing for those of the colorectum and stomach. During the first half of the 1990s, mortality and incidence rates of stomach and colorectal cancer have been on the decline for both men and women. For cancer of the stomach, this pattern has continued unabated since 1930. It is generally believed that this has occurred primarily because of decreased intake of preserved foods (due to the introduction of refrigeration around 1908), reducing the need for food-preservation strategies,³⁷ coupled with an increased intake of fresh fruits and vegetables.^38-42

From 1991 through 1995, the incidence rates for colorectal cancer decreased both in men (-10.3%) and in women (-4.9%), a continuation of a trend that began in the mid-1980s. The estimated number of new colorectal cancer cases in the United States decreased from 155,000 cases in 1987 to 129,400 in 1999. Colorectal cancer has been associated with several dietary factors, including red meat, fat, fiber, and the micronutrient folate. Recent epidemiologic studies largely support an association between meat consumption and colorectal cancer⁴³ but not total dietary or animal fat.^44-48 In support of this association, in the United States the per capita consumption of meat (beef, veal, pork, and lamb) decreased nearly 20% from 1971 to 1990.⁴⁹ High dietary fiber has been inversely associated with colon cancer in case-control studies^50,51 but not in prospective studies.⁵² Folic acid, which increased in the American diet in 1973 through the fortification of breakfast cereals and multivitamins, has also been associated with a decreased risk of colon cancer.⁵³

	HORMONES AND REPRODUCTIVE FACTORS

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It is now generally accepted that endogenous hormones play an etiologic role in cancers of the breast, prostate, endometrium, thyroid, and possibly the testes and ovary. Hormones are believed to contribute to carcinogenesis in these organs by promoting cell proliferation. In hormone-responsive tissues, such as breast epithelium, steroid hormones are necessary for normal growth and development; increased hormonal stimulation in these same tissue results in increasing proliferation and higher rates of malignant transformation. Trends in hormone-related cancers may in some cases be driven by changes in reproductive factors or population prevalence in exposures to exogenous hormones. During the past two decades, artificial increases in the incidence of cancers of the breast and prostate have been created by intensive screening efforts, while true increases have occurred for cancers of the testis, endometrium, ovary, thyroid, and breast. The impact of changing reproductive factors and screening efforts on the incidence and mortality of each of these hormone-associated cancers’ mortality and incidence rates is discussed below.

Breast Cancer
Breast cancer rates likewise seem to be strongly influenced by secular trends in age at first full-term pregnancy (FFTP).⁵⁴ After the rapid increase in breast cancer incidence rates that accompanied the widespread introduction of mammography in the 1980s, breast cancer mortality is now decreasing at a rate of approximately 1% per year. Although it is tempting to attribute this decrease to the impact of screening, analyses of age-specific birth cohorts shows that the secular patterns of these mortality changes are more complex than those predicted simply by changes in screening behavior.^54,55 Thus women in the oldest age group show increasing mortality, whereas women aged 50 through 59 show a consistent drop in mortality over the past 15 years, even before the possible impact of mammography. These patterns are consistent with those anticipated from secular changes in age at FFTP in women in the United States during this century. Thus the fall in mortality for women aged 50 through 59 during the 1980s and early 1990s is consistent with the decrease in mean age at first FFTP of women born between 1910 (mean age at FFTP, 25.5 years) and 1940 (mean age at FFTP, < 22 years).

Because age at FFTP has shown a substantial increase since 1940, the incidence of breast cancer will likely again increase as these birth cohorts move into the ages of higher breast cancer incidence.

Thyroid Cancer
Another notable trend in cancer incidence is the dramatic increase in thyroid cancer rates over the past three decades. Although the incidence of thyroid cancer in men has stabilized, the incidence in women has continued to increase (12.7% from 1991 to 1995). Up to age 35, women have four to five times the risk of thyroid cancer of men. The differential change in rates by sex and the high rate of thyroid cancer in women overall, compared with men,⁵⁶ suggests a probable role of hormones in thyroid cancer etiology. A number of epidemiologic studies have shown a strong association between certain reproductive factors and thyroid cancer risk. Specifically, a history of pregnancy has been associated with an elevated risk of thyroid cancer in several case-control studies, and risk was especially elevated among women with pregnancies terminated by spontaneous or induced abortions.^57-61 An alternative to the hormone hypothesis is that therapeutic radiation, an established risk factor for thyroid cancer, could account for the rising rate of disease. However, the high rates of radiation treatment for benign head and neck conditions between 1930 and 1960⁵⁶ would likely not account for the continued sex-specific increased incidence rates of thyroid cancer into the early 1990s.

Prostate Cancer
Intensified prostate cancer screening efforts during the mid-1980s, especially the use of the prostate-specific antigen (PSA) assay, resulted in large increases in prostate cancer incidence, with relatively small concurrent changes in mortality. Prostate cancer incidence from 1973 to 1987 increased by 52.4% for white males and 35.5% for African-American males, with markedly large increases occurring during the mid- to late 1980s through 1992. Rates from 1991 through 1995 show a reversal of this trend, as incidence and mortality began to decrease in both white (incidence, -24.5%; mortality, -5.1%) and African-American men (incidence, -4.8%; mortality, -1.7%) (Table 2). The trend for prostate cancer in African-American and white men is similar, with the exception that the trend is delayed approximately 2 years in African-American men.

The value of PSA screening to identify cases of asymptomatic prostate cancer remains controversial because the mortality benefit of detecting early-stage disease through this mechanism is unclear. Although it is generally accepted that early-stage detection of cancer results in better survival than late-stage detection, it is not clear what percentage of screened men with early-stage prostate cancer would actually progress to symptomatic disease. A recent study of untreated stage T1a prostate cancer reported that only 15% of the men enrolled in the study progressed to clinical disease.⁶² Any long-term benefits of PSA screening on prostate cancer mortality will not become apparent until the next decade. Prostate cancer mortality can be expected to fall to the extent that PSA screening effectively identifies the population at high risk of developing symptomatic disease, assuming that the majority of such men are effectively treated.

Endometrial Cancer
Trends in incidence and mortality from endometrial cancer are influenced by factors that alter estrogen and progesterone levels, including hormone-replacement therapy and the use of oral contraceptives (OC). The risk of endometrial cancer increases after increased exposure of endometrial tissue to estrogen that is unopposed by progestogen.^63-65 Thus estrogen-replacement therapy (ERT), in which estrogen is given to postmenopausal women without any progestogen, increases endometrial cancer risk. Beginning in 1966, a doubling of prescriptions for ERT to treat menopausal symptoms resulted in an epidemic of endometrial cancer that ended in the late 1970s,⁶⁶ when prescription patterns changed after epidemiologic proof that estrogen therapy was a cause of endometrial cancer. After 1976, progestogens were increasingly added to ERT to reduce or possibly eliminate this risk, and ERT treatment for menopausal symptoms among women who had not had a hysterectomy was largely discontinued. Rates of endometrial cancer decreased 26% between 1976 and 1987 but have now stabilized (Table 3). Oral contraceptives, which deliver an estrogen and a high-dose progestogen for 21 days of a 28-day cycle, decrease the risk of endometrial cancer by decreasing the duration of endometrial exposure to estrogen without a progestogen from the 2 weeks of a normal menstrual cycle to the 1 week when the OC is not taken.^67-69 Furthermore, endogenous estrogen levels are low during the 1 week when the OC is not used.

Ovarian Cancer
Mortality and incidence rates of ovarian cancer, which are strongly influenced by both OC use and reproductive experiences, declined from 1991 through 1995 in both white and African-American females. Declining rates of ovarian cancer are likely to be a consequence of extended OC use that interrupt ovulation and related cyclic hormonal changes. Causative hypotheses suggested to explain these observations involve "incessant ovulation," increased exposure to gonadotropins, and increased exposure to the high levels of estrogen that occur within the ovary during a normal menstrual cycle. The incessant ovulation hypothesis supposes that each cycle of ovulation, which includes repair of ovarian-surface epithelium, increases the risk of ovarian cancer.⁷⁰ All of these "etiologic factors" are reduced by pregnancies and OC use. Declining rates of ovarian cancer are likely to be a consequence of extended OC use.

	VIRUSES

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Liver Cancer
Beginning in the mid-1980s and continuing through 1995, liver cancer mortality and incidence substantially increased. Although it seemed in the early 1990s that rates were beginning to decline in African-American and white women, by 1995 mortality and incidence were again on the increase. Rates have consistently increased in men during this time frame. The reason for the increase has been hypothesized to include an increased prevalence of HCV and HBV infection.⁷¹ Although HBV infection has been well characterized as a risk factor for cirrhosis of the liver and liver cancer,⁷² HCV has only recently been identified and described as a hepatic carcinogen. Serologic testing for hepatitis C antibodies was first established in the United States in 1990, after which the rate of HCV infection began to decline. However, transmission through intravenous drug use, direct exposure to infected blood through other sources, and, to a lesser extent, sexual contact remain sources of HCV transmission. It is estimated that 180,000 new HCV infections occurred in the United States each year during the 1980s and that approximately 4 million people are currently infected with the virus.⁷³ Of the chronic carriers, approximately 10% to 20% will develop cirrhosis of the liver,⁷³ and approximately 2% to 7% will proceed to liver cancer within 20 years of infection.^71,74,75 The beneficial effects of HCV blood screening on liver cancer rates will depend on the average interval between infection and disease occurrence, which is thought to vary from 10 to 30 years. Nonetheless, the effect of HCV infection, as well as HBV infection, on liver cancer incidence could conceivably continue into the next several decades. Development of an effective treatment for currently infected individuals is needed to prevent the mortality rates of hepatocellular cancer from continuing their upward climb.

Cervical Cancer
The incidence and mortality for cervical cancer have been decreasing in both white and African-American women since the 1940s.⁵ Although it seemed that incidence rates for cervical cancer had begun rising in the mid-1980s after several decades of decline, rates again decreased in the early 1990s, by 12% in whites and 7% in African-Americans. Although infection with the human papilloma virus is believed to be a causal risk factor for cervical cancer,⁷⁶ trends in invasive cervical cancer, like those in prostate cancer, have been strongly influenced by screening. The regular use of cervical cytologic screening (PAP smears) to detect in situ cases has been most effective in reducing the rates of invasive cervical cancer.

	OTHER

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
The etiologic risk factors for NHL, CNS tumors, and multiple myeloma are not clearly understood. Although the exact causes of these diseases remain undetermined, recent trends in the incidence rates of all three of these cancers seem to have been at least partially influenced by changes in diagnostic techniques and classification procedures.

NHL
From 1973 to 1987, the incidence rates for NHL (67.4% in men and 46.8% in women) were on the increase. NHL rates continued to climb from 1991 through 1995 in both white men (mortality, 5.7%; incidence, 2.8%) and women (mortality, 7.0%; incidence, 2.9%). The largest secular increase in NHL incidence occurred for the extranodal NHL subgroup.^77,78

The increasing rates of NHL can be attributed to a number of factors, including improvements in diagnostic techniques and an increase in the number of immunodeficient patients susceptible to NHL because of the human immunodeficiency virus (HIV) epidemic.⁷⁸ Changes in diagnostic techniques, including the addition of immunohistochemical and cytologic methods, have resulted in a decline in the number of unspecified cases of NHL and the recognition of new cases that were not previously identified as malignant lymphomas.⁷⁸ These techniques have been especially useful in classifying extranodal primary lymphomas.^79-81 Nonetheless, trends in the mortality and incidence for NHL continue to be influenced by the lack of a fully developed standard classification system that reflects these advances in immunohistochemical and cytologic technology. A true increase in histologically high-grade lymphomas (including small noncleaved cell, large cell immunoblastic, and diffuse large cell lymphomas) occurred in the 1980s among immunodeficient populations consisting primarily of HIV-infected individuals⁸² and, to a lesser extent, organ transplant patients.⁸³ It is estimated that the cumulative incidence of NHL among individuals with HIV is 5% to 10%.⁸⁴ The HIV-infected population represents a pool of susceptible individuals who are at high risk of developing NHL through the next several decades.

CNS Cancer
The incidence rates for CNS tumors (22.2% in men and 34.9% in women) also increased from 1973 to 1987. However, recent trends in SEER data show that the mortality and incidence rates of CNS tumors are now decreasing in both men and women.

The incidence rates of CNS tumors, primarily brain tumors, increased from the mid-1980s through 1990. Among adults, this increase was largely restricted to men and women over 65 years of age, suggesting that these increases were actually the result of diagnostic improvements. The introduction of computed tomographic imaging technology in the United States in the mid-1970s and magnetic resonance imaging (MRI) equipment in the mid-1980s resulted in increased CNS tumor incidence rates, without uniform increases in mortality. Diagnostic improvements have also had an impact on the rates of childhood brain tumors; the incidence of these tumors increased 30.4% from 1973 through 1995, while mortality decreased 25.6% during the same period. Steep increases in rates followed the initial introduction of MRI equipment in 1982 with more gradual increases thereafter, as such equipment became available to nonresearch hospitals.^85-86 This hypothesis is further supported by the fact that the increase in incidence was largely restricted to low-grade brainstem and cerebral tumors⁸⁵ that are better visualized by MRI than computed tomography equipment.⁸⁷ This does not exclude a possible contribution of environmental factors to the increase in CNS rates observed during the 1970s and 1980s, but the pattern is more consistent with a temporary increase in rates due to diagnostic changes.

Multiple Myeloma
Diagnostic changes are also likely to have contributed to the rising rates of multiple myeloma from 1973 through 1990, although the causal determinants of this disease are unknown. Rates of multiple myeloma steadily climbed during this time period in all age groups, for both males and females. Rates were higher in African-Americans than whites and higher among males than females during the entire interval. However, like CNS tumors, the incidence rates of multiple myeloma fell in the early 1990s by 13.1% in males and 8.7% in females, although mortality rates continued to increase. The increase in incidence in the late 1970s and 1980s may be attributable to the increased availability of more sensitive laboratory diagnostic aids (serum protein electrophoresis, immunoelectrophoresis).⁸⁸ Ionizing radiation, pesticides, benzene, other solvents, and hair dyes have been inconsistently associated with increased risk of multiple myeloma in epidemiologic studies.⁸⁸

	FUTURE DIRECTIONS

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
The incidence and mortality from smoking-related cancers should continue to decline into the next decade because of reduced adult smoking rates over the past 40 years. However, if the recent increase in teen smoking rates continues, increases in adult smoking rates may follow, and the gains of these past few decades that resulted from the continued impact of legislation and huge public health educational campaigns could be lost. As we enter the next century, we must continue to search for successful public health interventions that will reduce the rate of smoking among young people.

We expect that the successful prevention and treatment efforts that have resulted in the downward trends for cancers of the stomach, cervix, and Hodgkin’s disease will continue. However, other cancers, particularly cancers of the breast and prostate and NHL, will require innovative strategies in cancer prevention and treatment to make further progress in reducing mortality and incidence.

Findings from the highly publicized 1998 tamoxifen trial provide strong support that breast cancer is preventable among high-risk women.⁸⁹ In this randomized trial, tamoxifen reduced the risk of invasive breast cancer by 49% and of noninvasive breast cancer by 50%. It is still unknown, however, whether tamoxifen benefits women with genetic susceptibility to breast cancer or whether the results of this trial apply to women of ethnic minority groups. The benefits of tamoxifen must be weighed against the health risks, the most publicized of which is a substantial increased risk of endometrial cancer. A new clinical trial supported by the National Cancer Institute will test the benefits and risks of using tamoxifen versus raloxifene (a drug used in the treatment of osteoporosis) in the prevention of breast cancer.

Chemopreventive trials to decrease the incidence of and mortality of prostate cancer are ongoing. To determine the benefit of finasteride—an inhibitor of 5-alpha-reductase activity (an enzyme in the androgen-metabolism pathway)—on prostate cancer risk, the National Cancer Institute has invested in a nationwide trial investigating long-term finasteride treatment (7 years) as a prostate cancer chemopreventive agent in 18,000 healthy adult men. Although the nationwide trial is ongoing, the chemopreventive potential of finasteride was recently challenged in a study of a small group of men with elevated serum PSA levels. In this study, even though the drug effectively lowered serum PSA levels, more men using finasteride progressed to prostate cancer than did men who did not take the inhibitor.⁹⁰ Hypotheses for this unexpected finding have included the idea that finasteride alters prostate size and, therefore, prostate-tumor detection rates or—more ominously—that finasteride alters the balance of dihydrotestosterone and testosterone levels in a way that increases prostate cancer risk.

In conclusion, cancer incidence rates during the 1980s were increasing for several cancers: those of the breast, testis, and brain, as well as NHL and multiple myeloma.⁴ These increases created a widespread concern that a cancer epidemic attributable to environmental and occupational synthetic chemical exposures existed. In 1991, we argued that there was sufficient information on the causes of cancer largely outside the context of agricultural or industrial chemicals to explain most, if not all, of these changing patterns of cancer incidence.⁴ Data from the SEER program on more recent trends in cancer incidence and mortality for the period 1991 through 1995 show that cancer rates are generally now on the decline. These data further argue against a cancer epidemic caused by synthetic chemical carcinogens and argue that previous increases were explicable through the influence of other risk factors combined, in some cases, with the implementation of more sophisticated diagnostic tools. It is increasingly obvious that we are making major strides in reducing the cancer burden in this country by advances in cancer prevention, early diagnosis, and treatment. These advances, which are just now beginning to be realized, may herald a sustained reduction in cancer rates that will parallel the remarkable decline in heart disease and stroke mortality that has been documented during the past three decades.

	ACKNOWLEDGMENTS

 
Supported by grants no. CA63464-04, CA17054-21, N01-PC-67010, and PHI-050-N-8709-51528 from the National Cancer Institute, Bethesda, MD.

	REFERENCES

TOP ABSTRACT INTRODUCTION CANCER TRENDS TOBACCO USE AND SMOKING ULTRAVIOLET RADIATION DIET HORMONES AND REPRODUCTIVE... VIRUSES OTHER FUTURE DIRECTIONS REFERENCES

 
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Submitted August 31, 1999; accepted February 10, 2000.

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