The Prostate 16:187-197 (1990)
Epidemiologic Evidence Regarding Predisposing Factors To Prostate Cancer Bob S. Carter, H. Ballantine Carter, and John T. lsaacs The Department of Epidemiology, Clinical Epidemiology Program (6.S.C.), The Johns Hopkins University School of Hygiene and Public Health, and The Brady Urological Institute (H.B.C., J.TI.), The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland In 1990, prostate cancer will be the most common cancer diagnosed in U.S. men and will be the second-leading cause of cancer mortality in these men. One in ten U.S. men will develop prostate cancer in his lifetime. Twenty thousand prostate cancer cases occur each year in men under the age of 65. The average number of years of life lost for a man dying of prostate cancer is nine. In addition, both incidence and mortality of prostate cancer are increasing. A review of the literaturexegarding prostate cancer is timely in light of recent studies examining possible predisposing factors for this disease. In this review, a framework for understanding genetic and environmental factors which may predispose to prostate cancer is presented. The identification of factors which predispose to clinical prostate cancer offers the possibility of lowering the incidence and mortality of prostate cancer in the United States. Epidemiologic evidence regarding possible predisposing factors to prostate cancer is reviewed.
Key words: epidemiology, genetic risk factors, environmental risk factors
INTRODUCTION: PROSTATE CANCER IN 1990
The incidence and mortality of prostate cancer reveal the significant impact of this disease in the United States. From 1973 to 1985, the age-adjusted prostate cancer incidence increased approximately 22% from 68.4/100,000 men to 83.4/100,000 men among U.S. whites and blacks [ 13. It is estimated that there are 11 million men in the United States with lesions within their prostate which are histologically identifiable as prostate cancer [2]. Over 100,OOO new cases of prostate cancer will be diagnosed in the United States in 1990, making prostate cancer the most common cancer diagnosed in U.S. males [3]. Prostate cancer represents 21% of all newly diagnosed cancers in U.S. males each year [3]. One in ten U.S. men will develop prostate cancer in his lifetime [4]. Mortality from prostate cancer also represents a significant problem. From 1973 to 1985, the age-adjusted mortality from prostate cancer increased slightly from 20.1/100,000 men to 21.5/100,000 men among U.S. whites [l]. In 1990, the total
Received for publication November 1 I , 1989; accepted December 1 1, 1989. Address reprint requests to Dr. John T. Isaacs, Department of Urology, The Johns Hopkins Hospital, Baltimore, MD 21205. 0 1990 Wiley-Liss, Inc.
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annual deaths from this disease will approach 30.000, making this the second-leading cause of cancer-related deaths in United States men [3]. Twenty thousand cases of prostate cancer will occur in men under the age of 65 in 1990 [5]. This represents more than all the renal cancers and leukemias in men of all ages, more than all brain and CNS tumors of men and women of all ages, and will almost equal the number of buccal cavitylpharynx and rectal cancers in men of all ages [3]. Although 80,000 cases occur each year in men over the age of 65, the impact of this disease in these later years is still significant. This is because even though the average life expectancy of U.S. men at birth is near 72 years, once a man has reached the ages of peak prostate cancer incidence, 70-74 years old, his life expectancy is another 9-11.5 years if he does not have prostate cancer [6]. Horm and Sondik recently calculated the total person years of life lost (PYLL) and the average years of life lost (AYLL) due to prostate cancer in 1970 and 1984 [7]. The PYLL is the sum of the difference between the actual age at death and the expected remaining lifetime for each.person who died of prostate cancer. The AYLL represents how many years of life persons dying of prostate cancer lose on average. The annual PYLL due to prostate cancer increased from 156,281 in 1970 to 228,597 in 1984. Based on the estimated number of deaths from prostate cancer in 1990, the PYLL due to prostate cancer in 1990 will equal 270,000. The increases in the PYLL for prostate cancer from 1970 to 1984 reflect the shift in age distribution of the U.S. population to an older population as well as a reduction in competing causes of death such as cardiovascular disease. The AYLL for prostate cancer was 9.1 years in 1970 and 9.0 years in 1984. The AYLL highlights the fact that men who die of prostate cancer experience a significant reduction in the length of their lives-an average of nine years.
BACKGROUND CONCERNING PREDISPOSING FACTORS TO PROSTATE CANCER
The multi-step nature of carcinogenesis provides an important framework for understanding why there is a need to explore predisposing factors to prostate cancer. Considerable evidence supports the concept that multiple events are required to transform a normal cell into a malignant one. Such multistep progression predicts that a cancer will go through various premalignant stages detectable based on changes in histologic morphology. This is highly relevant to prostate cancer because millions of U.S. men have lesions which histologically appear to be prostate cancer. Autopsy studies show that nearly one-third of men over the age of 45 have lesions within the prostate which are histologically identifiable as prostate cancer [8]. Fortunately, the vast majority of these histologic cancers do not give rise to clinical symptoms in the lifetime of the host. A variety of terms have been used to describe these histologic cancers found at autopsy. Some of these terms include latent, microscopic, incidental, and dormant cancers. These terms, however, have implications that are often not correct. For example, “latent” implies that the biologic potential of these histologic prostatic cancer lesions is known, whereas it is currently impossible to say what the natural history of such a lesion may be. “Microscopic” prostate cancer is also misleading in that many of these cancers are large. Data from the German Cancer Registry reveals that one-third of these cancers are greater than 1 cm in diameter [8]. The term “histologic” prostate cancer, which implies nothing about the biologic
Predisposing Factors to Prostate Cancer
189
potential of the tumor, will be used to describe the prostate cancer which does exist in many older men based on autopsy data. At issue is whether or not these histologic cancers have completed all the steps required for a cancer to become clinically evident. If all histologic cancers have undergone these steps, only time would be required before all of these histologic tumors become clinically manifest. On the other hand, if histologic prostate cancers have not yet undergone all the steps necessary to become clinically evident, there exists the possibility of identifying the factors which lead to the progression from a histologic to a clinically evident tumor. One may be able to prevent clinical prostate cancer by reducing exposure to these progression factors. Recent work by Carter et al. has presented evidence that histologic prostate cancer does requires further steps to become clinically evident [9]. This evidence is based on the following data. It is known that there is a marked international variation in the incidence of clinical prostate cancer. The highest rates of clinically diagnosed prostate cancer are in U.S. blacks, with rates near 100/100,000 male population. In contrast are the very low rates (
Epidemiologic Evidence Regarding Predisposing Factors To Prostate Cancer Bob S. Carter, H. Ballantine Carter, and John T. lsaacs The Department of Epidemiology, Clinical Epidemiology Program (6.S.C.), The Johns Hopkins University School of Hygiene and Public Health, and The Brady Urological Institute (H.B.C., J.TI.), The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland In 1990, prostate cancer will be the most common cancer diagnosed in U.S. men and will be the second-leading cause of cancer mortality in these men. One in ten U.S. men will develop prostate cancer in his lifetime. Twenty thousand prostate cancer cases occur each year in men under the age of 65. The average number of years of life lost for a man dying of prostate cancer is nine. In addition, both incidence and mortality of prostate cancer are increasing. A review of the literaturexegarding prostate cancer is timely in light of recent studies examining possible predisposing factors for this disease. In this review, a framework for understanding genetic and environmental factors which may predispose to prostate cancer is presented. The identification of factors which predispose to clinical prostate cancer offers the possibility of lowering the incidence and mortality of prostate cancer in the United States. Epidemiologic evidence regarding possible predisposing factors to prostate cancer is reviewed.
Key words: epidemiology, genetic risk factors, environmental risk factors
INTRODUCTION: PROSTATE CANCER IN 1990
The incidence and mortality of prostate cancer reveal the significant impact of this disease in the United States. From 1973 to 1985, the age-adjusted prostate cancer incidence increased approximately 22% from 68.4/100,000 men to 83.4/100,000 men among U.S. whites and blacks [ 13. It is estimated that there are 11 million men in the United States with lesions within their prostate which are histologically identifiable as prostate cancer [2]. Over 100,OOO new cases of prostate cancer will be diagnosed in the United States in 1990, making prostate cancer the most common cancer diagnosed in U.S. males [3]. Prostate cancer represents 21% of all newly diagnosed cancers in U.S. males each year [3]. One in ten U.S. men will develop prostate cancer in his lifetime [4]. Mortality from prostate cancer also represents a significant problem. From 1973 to 1985, the age-adjusted mortality from prostate cancer increased slightly from 20.1/100,000 men to 21.5/100,000 men among U.S. whites [l]. In 1990, the total
Received for publication November 1 I , 1989; accepted December 1 1, 1989. Address reprint requests to Dr. John T. Isaacs, Department of Urology, The Johns Hopkins Hospital, Baltimore, MD 21205. 0 1990 Wiley-Liss, Inc.
188
Carter et al.
annual deaths from this disease will approach 30.000, making this the second-leading cause of cancer-related deaths in United States men [3]. Twenty thousand cases of prostate cancer will occur in men under the age of 65 in 1990 [5]. This represents more than all the renal cancers and leukemias in men of all ages, more than all brain and CNS tumors of men and women of all ages, and will almost equal the number of buccal cavitylpharynx and rectal cancers in men of all ages [3]. Although 80,000 cases occur each year in men over the age of 65, the impact of this disease in these later years is still significant. This is because even though the average life expectancy of U.S. men at birth is near 72 years, once a man has reached the ages of peak prostate cancer incidence, 70-74 years old, his life expectancy is another 9-11.5 years if he does not have prostate cancer [6]. Horm and Sondik recently calculated the total person years of life lost (PYLL) and the average years of life lost (AYLL) due to prostate cancer in 1970 and 1984 [7]. The PYLL is the sum of the difference between the actual age at death and the expected remaining lifetime for each.person who died of prostate cancer. The AYLL represents how many years of life persons dying of prostate cancer lose on average. The annual PYLL due to prostate cancer increased from 156,281 in 1970 to 228,597 in 1984. Based on the estimated number of deaths from prostate cancer in 1990, the PYLL due to prostate cancer in 1990 will equal 270,000. The increases in the PYLL for prostate cancer from 1970 to 1984 reflect the shift in age distribution of the U.S. population to an older population as well as a reduction in competing causes of death such as cardiovascular disease. The AYLL for prostate cancer was 9.1 years in 1970 and 9.0 years in 1984. The AYLL highlights the fact that men who die of prostate cancer experience a significant reduction in the length of their lives-an average of nine years.
BACKGROUND CONCERNING PREDISPOSING FACTORS TO PROSTATE CANCER
The multi-step nature of carcinogenesis provides an important framework for understanding why there is a need to explore predisposing factors to prostate cancer. Considerable evidence supports the concept that multiple events are required to transform a normal cell into a malignant one. Such multistep progression predicts that a cancer will go through various premalignant stages detectable based on changes in histologic morphology. This is highly relevant to prostate cancer because millions of U.S. men have lesions which histologically appear to be prostate cancer. Autopsy studies show that nearly one-third of men over the age of 45 have lesions within the prostate which are histologically identifiable as prostate cancer [8]. Fortunately, the vast majority of these histologic cancers do not give rise to clinical symptoms in the lifetime of the host. A variety of terms have been used to describe these histologic cancers found at autopsy. Some of these terms include latent, microscopic, incidental, and dormant cancers. These terms, however, have implications that are often not correct. For example, “latent” implies that the biologic potential of these histologic prostatic cancer lesions is known, whereas it is currently impossible to say what the natural history of such a lesion may be. “Microscopic” prostate cancer is also misleading in that many of these cancers are large. Data from the German Cancer Registry reveals that one-third of these cancers are greater than 1 cm in diameter [8]. The term “histologic” prostate cancer, which implies nothing about the biologic
Predisposing Factors to Prostate Cancer
189
potential of the tumor, will be used to describe the prostate cancer which does exist in many older men based on autopsy data. At issue is whether or not these histologic cancers have completed all the steps required for a cancer to become clinically evident. If all histologic cancers have undergone these steps, only time would be required before all of these histologic tumors become clinically manifest. On the other hand, if histologic prostate cancers have not yet undergone all the steps necessary to become clinically evident, there exists the possibility of identifying the factors which lead to the progression from a histologic to a clinically evident tumor. One may be able to prevent clinical prostate cancer by reducing exposure to these progression factors. Recent work by Carter et al. has presented evidence that histologic prostate cancer does requires further steps to become clinically evident [9]. This evidence is based on the following data. It is known that there is a marked international variation in the incidence of clinical prostate cancer. The highest rates of clinically diagnosed prostate cancer are in U.S. blacks, with rates near 100/100,000 male population. In contrast are the very low rates (
