Prostate cancer risk in African Americans

African Americans are more likely to develop — and die from — prostate cancer than others. But why?

This year, the American Cancer Society estimates that nearly 1.5 million Americans will be diagnosed with some form of cancer — and that figure doesn’t even include more than 1 million cases of certain skin cancers. The organization estimates that cancer will also claim 562,340 lives in 2009. Scientific evidence shows that about one-third of those deaths could have been prevented by making lifestyle changes. Smoking, being overweight or obese, not exercising, and eating a poor diet — all modifiable risk factors — have been linked to cancer (as well as heart disease, diabetes, and many other conditions).

Although several studies indicate that the risk of dying from prostate cancer increases with obesity, and that a diet high in saturated fat can up the risk of developing the disease, factors that can’t be changed seem to account for most prostate cancers. These include family history, age, and race and ethnicity. For example, recent genetic studies have found that a strong familial predisposition may be responsible for about 5% to 10% of prostate cancers, which could be as many as 19,228 cases this year. Men with a first-degree relative (brother or father) with prostate cancer are more than two-and-a-half times as likely to develop the disease as a man with no affected family members.

Prostate cancer is not a young man’s disease (see Table 1 below). The median age at diagnosis is 68. Doctors diagnose most prostate cancers in men who are age 65 or older. Although most of these men die with prostate cancer, not from it, the median age of men who do succumb to the disease is 80. Because many diseases become more prevalent with increasing age, none of this may be particularly surprising.

What may be surprising is that race and ethnicity significantly influence who gets prostate cancer and who dies from it (see Table 2 below). African American men have, by far, the highest incidence of the disease: they are roughly 1.6 times more likely to develop prostate cancer than whites and 2.6 times more likely than Asian Americans. The gap in mortality rates is even more dramatic — African Americans are more than twice as likely to die of prostate cancer as whites and about five times more likely to die of it than Asian Americans.

Prostate-specific antigen (PSA) screening, which became widely accepted in the mid-1990s and resulted in earlier diagnosis, helped close the gap in five-year survival rates between African Americans and whites over the past 25 years (see Table 3 above). Access to care and cancer treatments seem to have improved, too. But the disparities remain, and researchers want to know why.

Diet, obesity, and metabolic factors

Noting that differences in prostate cancer incidence among races and ethnicities could be due to modifiable lifestyle factors, California researchers tested the impact of diet, physical activity, body size, and migration patterns on risk in a population-based, case-control study. They recruited 1,655 white, African American, Chinese American, and Japanese American men in Los Angeles, San Francisco, Hawaii, Vancouver, and Toronto who had been diagnosed with prostate cancer. These cases were then compared with the histories of 1,645 control subjects with normal PSA levels — men of diverse ethnicity who were in the same age range and lived in the same regions. All of the men were questioned in detail about their diet, physical activity, and changes in body weight over time.

The team found that fat intake, specifically the consumption of saturated fat, accounted for about 15% of the difference in prostate cancer incidence between whites and Asian Americans and only 10% of the difference between whites and African Americans. (Interestingly, the risk of prostate cancer among Asian Americans born outside the United States and Canada increased the longer they lived in North America.) Differences in prostate cancer incidence were unrelated to intake of other types of nutrients, such as carbohydrates, protein, and polyunsaturated fat; physical activity; and body mass.

But not every study has come to the same conclusion. Many subsequent studies have shown that obesity may increase the risk of prostate cancer. Some have also shown that a higher body mass index (BMI) is associated with more advanced disease, and that obese prostate cancer patients, like other cancer patients with multiple medical problems, die earlier in the course of their cancer than patients at a healthy weight.

To shed light on the question of whether racial differences in obesity might explain the racial gap in prostate cancer outcomes, as well as whether obesity might make cancer more likely to recur, researchers examined data from 3,162 men at nine military medical centers in the United States. All of the men had been diagnosed with prostate cancer and had had a radical prostatectomy; pathological data, such as the cancer stage and Gleason score, along with age, race, height, weight, and PSA level, were recorded for each patient.

The researchers found that, in comparison with whites, African American men were more likely to be obese, which is defined as having a BMI of 30 or more. (See “Calculating BMI,” below.) They were also more likely to have higher PSA levels and more advanced cancers — and to have positive surgical margins, meaning that when the surgeon removed the prostate, some cancer cells were left behind. An increased BMI also predicted higher rates of biochemical recurrence, which was defined as one PSA test score greater than 0.2 ng/ml or two test scores of 0.2 ng/ml at least three months apart after surgery.

Exactly how obesity could lead to the progression of prostate cancer isn’t clear. But researchers note, for example, that abdominal fat is associated with insulin resistance and too much insulin in the blood. (Produced by the pancreas, insulin helps regulate blood sugar.) High blood levels of insulin and insulin-like growth factors (IGFs) may contribute to disease progression, as IGF-1 stimulates the growth of prostate cells. Hormonal shifts may also be to blame. Obesity is associated with lower levels of sex hormone–binding globulin, which may increase the amount of testosterone available for use in the body. Higher levels of testosterone can fuel the growth of tumors.

But a July 2009 study throws some cold water on those hypotheses. Noting that prostate cancer and metabolic syndrome, a cluster of conditions that raise the risk of diabetes and heart disease, both have rates that vary by race and ethnicity, Michigan researchers looked for a link between the two. (See “What is metabolic syndrome?” above for details on this condition.) Studying 637 prostate cancer patients and 244 control subjects, they found that metabolic syndrome was only marginally related to an increased risk of prostate cancer in African American men. They then sorted the patients by disease stage and found, somewhat counterintuitively, that African American men with organ-confined disease were more likely to have a history of metabolic syndrome than men in the control group. There was no association between African American men with advanced-stage disease and metabolic syndrome. Furthermore, they found that obesity was unrelated to prostate cancer risk in African Americans. (To read these three studies on the possible link between diet and obesity and prostate cancer incidence and mortality, see “Impact of diet and obesity,” below.)

Socioeconomic status

Findings from some early studies suggested that differences in socioeconomic status between African Americans and whites may be responsible for some, if not all, of the elevated incidence in cancer among African Americans. Researchers from the National Institutes of Health tested that hypothesis using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and census data from millions of people in three large metropolitan areas: San Francisco and Oakland, Detroit, and Atlanta. They found no statistically significant association between income or educational level and the higher incidence of prostate cancer in African Americans, leading them to speculate that genetic traits or cultural factors unrelated to socioeconomic status might be to blame.

A later study came to a similar conclusion. Researchers reviewed data from 3,173 men diagnosed with prostate cancer. Advanced-stage prostate cancer was detected more frequently in African Americans and Hispanics compared with whites. Researchers then examined questionnaires from participants about their educational level, income, employment status, and whether they had medical insurance, as well as data about other health conditions. After taking all of this information into account, they found that socioeconomic, clinical, and pathological factors account for increased risk in Hispanic men, but not in African Americans.

Investigators affiliated with the Southwest Oncology Group (SWOG) took the research one step further by looking to see if racial disparities in survival persist even when patients with the same disease stage receive identical treatment and follow-up care. (Quality of care and treatment choices may be affected by employment and insurance coverage, both of which are considered socioeconomic factors.) They examined the records of 1,843 prostate cancer patients enrolled in their clinical trials and found that African Americans were 21% more likely to die of advanced-stage prostate cancer than whites, even after taking other measures of socioeconomic status into consideration. (To read this study and others on race, socioeconomic status, and prostate cancer incidence and mortality, see “Impact of socioeconomic status,” below.)

The upshot? SWOG investigators speculate that differences in tumor biology associated with race or ethnicity, such as the way the body metabolizes chemotherapy drugs, might make cancers in African Americans more aggressive or resistant to treatment. But until data supporting that explanation become available, it remains speculation.

Genetic variants

Knowing that the development and progression of prostate cancer involve testosterone and other androgens, or male hormones, University of Pennsylvania researchers began studying a gene called CYP3A4, which is involved in the metabolism of testosterone. They looked at the coding, or “recipe,” for the gene in white men and discovered that the sequence of nucleotides in a section of the CYP3A4 gene in most of them was AGGGCAAGAG. (See “What’s a nucleotide?” below.) But in some of the men, the sequence of nucleotides was AGGGCAGGAG.

The researchers then looked at the sequence of nucleotides in 230 white men with prostate cancer. They found that the group of men who carried the genetic variant — AGGGCAGGAG — had higher-stage tumors and higher Gleason scores than the men who did not carry the genetic variant. The genetic variant was also more common in patients who had no family history of prostate cancer and who were diagnosed later in life. There was no significant association between the genetic variant and PSA level at the time of diagnosis.

Why might the variation in nucleotide sequence matter? Perhaps, the researchers hypothesized, if the gene could no longer metabolize testosterone properly, more testosterone would be available for conversion into dihydrotestosterone, the hormone mainly involved in the regulation of prostate cell growth. Taking the theory one step further, the genetic variant could lead to the development of prostate cancer.

A year later, researchers in Cleveland examined the frequency of the genetic variant among healthy men in different racial and ethnic groups. They did not find the variant in any of the 80 Asian men they tested. Among 117 white men, 7% carried at least one copy of the genetic variant, and among 121 Hispanic men, 20% did. (Remember, we receive one copy of our genes from each parent.) In contrast, 81% of 116 African Americans carried at least one copy of the genetic variant.

Next, they studied 174 African American prostate cancer patients. In this group, 83% carried at least one copy of the genetic variant, which is similar to the rate among healthy African American men. But the men with prostate cancer were significantly more likely to have two copies of the genetic variant — and those men with two copies were also more likely to have more advanced prostate cancer when they were diagnosed. Several subsequent studies by other research teams came to similar conclusions.

Originally published November 2009; last reviewed February 24, 2011.