Urologic Oncology: Seminars and Original Investigations
Seminar articlesThe association between obesity and the progression of prostate and renal cell carcinoma
Introduction
Obesity has become a major health problem in this country, affecting over 30% of the adult population [1]. In the recently published National Health and Nutrition Examination Survey (NHANES) which obtained measured height and weight data from a nationally representative sample of over 4000 U.S. adults, the age-adjusted prevalence of obesity had increased from 22.9% in the 1988–1994 survey to 30.5% in the more current 1999–2000 survey [1]. This trend was seen in all age and ethnic groups. The incidence of severe or “morbid” obesity had nearly tripled over this time, from 0.78% in 1990 to 2.2% in 2000, with rates as high as 6% in black women and 3.4% in persons who had not completed high school [2]. Even more concerning is that childhood obesity has also increased dramatically with an estimated current prevalence of 15% in children aged 6–19 years [3]. Obesity is associated with many chronic medical problems including diabetes, hypertension, heart disease, stroke and hypercholesterolemia, and it was estimated that health care costs attributable to obesity in this country amounted to $99 billion per year in 1995, and currently accounts for up to 7% of the total health care budget [4], [5]. Americans spend about $30 billion per year on weight reduction programs, most of which are unsuccessful [6]. The importance of obesity as a national epidemic in this country cannot be overstated.
In addition to its association with the development of several chronic medical conditions, obesity has also been linked to several types of cancer [7], [8]. Animal studies have consistently shown that animals forced to decrease energy intake have lower cancer incidences than animals allowed to eat as much as they want [9]. A recent large prospective cohort investigation confirms multiple previous studies suggesting an association between obesity and cancer development in humans [10]. This study monitored more than 900,000 U.S. adults who were free of cancer at enrollment in 1982, over a 16-year period of follow-up, and the relationship between body mass index (BMI) and death from cancer was assessed for various cancer types. The heaviest members of this cohort (BMI > 40 kg/m2) had 52% and 62% higher cancer death rates for men and women respectively, compared to those of normal weight. In both men and women, BMI was also associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney. Significant trends were also noted for cancer of the stomach and prostate in men, and cancers of the breast, uterus, cervix, and ovaries in women. It was estimated that the current overweight and obesity patterns in this country could alone account for 14% of all deaths from cancer in men and 20% of those in women [10]. While the biologic mechanisms linking obesity to cancer risk are not yet clear, this and other studies suggest that body mass may indeed play an important role in the initiation and progression of some malignancies.
Section snippets
Obesity and prostate cancer
The epidemiologic evidence linking obesity to the risk of developing prostate cancer has been inconclusive. Although several large epidemiological studies have found a positive relationship between prostate cancer incidence and increased BMI, a similar number of studies show no association, and some show a protective effect [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]. A large cohort study of 135,000 Swedish construction workers followed
Outcome after radical prostatectomy
To explore the hypothesis that obesity predicts more aggressive disease in clinically localized prostate cancer, two recent studies investigate the possibility that obesity is related to higher recurrence rates after radical prostatectomy (RP) [28], [29]. Both studies were retrospective analyses of multi-institutional series and examined the relationship between BMI and the risk of prostate-specific antigen (PSA) recurrence in large multiethnic populations. In both studies, obesity resulted in
Potential biologic explanations
The biologic processes underlying the association between prostate cancer progression and obesity are unknown, although several potential mechanisms have been proposed [30]. Since prostate cancer is a hormonally dependent malignancy, hormonal alterations associated with obesity may have some role. Although obesity is generally associated with higher estrogen and lower testosterone levels, which on the surface might seem protective, it also results in lower levels of sex hormone-binding globulin
Obesity and kidney cancer
While much less common than prostate cancer, the risk of kidney or renal cell cancer (RCC) also appears to be related to obesity. A direct relationship between obesity and kidney cancer risk, especially in women, has been consistently noted in past studies. In one of the first published case-control studies investigating this relationship, 495 cases and 697 controls from the Minneapolis-St. Paul, Minnesota region were analyzed [47]. A higher BMI was found to be a major risk factor for women,
Potential mechanisms
Several potential and interrelated mechanisms may be responsible for the increased risk of RCC with obesity [65]. Some of the biologic processes proposed for prostate cancer may also have a role in kidney cancer. Although IGF-1 has not been found to have as strong an association to RCC as prostate cancer, some studies suggest a possible relationship, and insulin and leptin levels may also have a role [66], [67], [68]. Obesity may increase the risk of RCC in women by increasing blood levels of
Conclusions
While epidemiologic studies report conflicting results on the relationship between obesity and prostate cancer risk, several imply that obesity may be more closely related to prostate cancer death. Thus, obesity may be one of many risk factors that are responsible for the promotion of latent prostate cancer to a more significant form of disease. Several potential biologic mechanisms have been proposed to explain why obesity might result in more aggressive disease, including alterations in
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