Diseases / Research

Prostate Cancer

Prostate cancer

Prostate ducts (white spaces) are seen lined with cancer cells (stained purple) with connective tissue (stained blue).

Photo by Fred Hutch

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 Fred Hutch researchers are making breakthrough contributions to improving prostate cancer detection and understanding risk, and developing innovative treatment options.

Our preventon and early detection research is focused on lifestyle factors and genetics.  One Hutch research team discovered the genetic mutations that increase the risk for prostate cancer.  Our researchers are also working to better uderstand disease progression and why some some tumors are resistance to treatment.

Fast Facts

  • Prostate cancer affects the prostate, a walnut-sized male sex gland located just below the bladder, and occurs most often in men older than 55.
  • The majority of prostate cancers that are detected by screening tend to be small and grow slowly. Chances of surviving most early-stage, low-grade prostate cancers are excellent.
  • Prostate cancer treatment is controversial. Many men with small cancers will not benefit from treatment, because the cancer grows so slowly that it will cause no problems. But it isn't yet possible to determine which prostate cancers will grow rapidly, making treatment decisions very difficult.
  • Prostate cancer ranks as the most common form of cancer among men in the United States and is second only to lung cancer in the number of annual cancer deaths among U.S. men.

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Prevention & Causes

Fred Hutch experts are identifying key factors that affect a person's prostate cancer risk:

Genetic mutation  A team of researchers led by Janet Stanford, Ph.D., of Fred Hutch has discovered that mutations in the gene BTNL2, which encodes a protein involved in regulating T-cell proliferation and cytokine production – both of which impact immune function – increase the risk of developing prostate cancer. Learn more >

Circumcision – Dr. Jonathan Wright and colleagues have determined that circumcision before a male’s first sexual intercourse is associated with a reduced risk of prostate cancer, which may be related to the procedures ability to hinder infection and inflammation that may lead to prostate cancer.  The study, which included Drs. Daniel Lin and Janet Stanford, included 3,399 men and determined that circumcised men were 15 percent less likely to develop prostate cancer than uncircumcised men. The reduced relative risk applied for both less and more aggressive forms of the cancer. Learn more >

Deep-fried foods increase risk  Regular consumption of deep-fried foods such as French fries, fried chicken, fried fish and doughnuts is associated with an increased risk of prostate cancer, and the effect appears to be slightly stronger with regard to more aggressive forms of the disease. The findings were published in 2013 by Drs. Stanford, Marian Neuhouser and collaborators. Learn more >

Diet – Separate studies led by Drs. Alan Kristal and Ulrike Peters have found a connection between greater consumption of dark green and cruciferous vegetables, especially broccoli and cauliflower, and decreased risk of aggressive prostate cancer. That research also shows that eating more tomatoes and fruit does not help prevent prostate cancer. Drs. Lin, Neuhouser and Kristal are also examining how a biologically active compound in broccoli called sulforaphane affects mechanisms in prostate tissue that are related to cancer development. Learn more >

Estrogen pathway genes  Variations in estrogen-related genes may contribute to prostate cancer risk, according to a population-based case-control study conducted by Hutchinson Center investigators and colleagues. Study authors include Drs. Stanford, Ziding Feng and collaborators. Additional research may assess genetic variants in genes that are part of this pathway in specific subsets of patients with particular environmental exposures or genetic backgrounds.

Family history – The Prostate Cancer Genetic Research Study (PROGRESS) is a nationwide research project exploring why some families have several men, often in multiple generations, who develop prostate cancer. Discovering the inherited genetic mutations for prostate cancer in families and how they work will hopefully provide new clues to help diagnose, treat, cure and even prevent prostate cancer in future generations.  A whole-exome sequencing project in multiple members of selected hereditary prostate cancer (HPC) families recently revealed two genetic mutations that may contribute to risk of HPC.  Current research efforts focus on validation of these findings.  In addition, Center investigators are collaborating with multiple groups in the discovery and validation of genetic markers called SNPs that are associated with risk of developing prostate cancer in both HPC families and among men without a strong family history.  For example, Dr. Stanford contributes to the African American Genome-wide Association Study and the international PRACTICAL Study that recently validated 23 SNPs that are associated with risk of developing prostate cancer.

HOXB13 genetic mutation  An association of a rare HOXB13 gene mutation with prostate cancer risk in the general population suggests that the mutation may be associated with features of more aggressive disease, according to a study co-authored by Drs. Stanford, Elaine Ostrander, Marni Stott-Miller and collaborators.

Medication – Fred Hutch’s Program in Prostate Cancer Research studies several types of commonly used medications to determine if they affect prostate cancer risk or outcomes. These medications include:

  • Aspirin and NSAIDs – A population-based, case-control study led by Drs. Stanford, Ziding Feng, Peter Nelson and Ulrike Peters that was published in 2010 observed a 21 percent reduction in prostate cancer risk among regular aspirin users. Inflammation may play in the development of prostate cancer, so the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) is a growing focus for scientists and requires additional research.

  • Statins and increased risk – An initial study published in 2008 and led by Dr. Stanford showed that obese men who take statins to control their cholesterol, particularly for extended durations, have an increased risk of prostate cancer. The study found non-obese men do not have the same risk. The study’s findings warrant further investigation, particularly since some studies have suggested that statins may be associated with reducing cancer risk.

  • Statin and decreased mortality risk – Statins taken to lower blood cholesterol levels – taken before and at the time of prostate cancer diagnosis are associated with a decrease in risk of prostate cancer-specific mortality, according to a Hutchinson Center study conducted by Drs. Stanford, Feng and collaborators. The study also observed that statins taken before or at the time of prostate cancer diagnosis were unrelated to prostate cancer recurrence or progression. Learn more >

  • Finasteride – Dr. Mary Redmand and colleagues associated with the Prostate Cancer Prevention Trial determined that finasteride (Proscar), a common therapy for the treatment of an enlarged prostate or BPH, helped reduce the incidence of prostate cancer by about 25 percent. Additionally, researchers found that participants who took finasteride and did develop high-grade cancer had their tumors detected earlier and at a less extensive stage.

  • Metformin – Men taking the diabetes drug metformin had significantly lower risk of a prostate cancer diagnosis, according to a population-based case-control study by Drs. Stanford and Jonathan Wright. Dr. Wright is now studying metformin as a cancer therapy as well as the drug’s effect at the tissue level.

Obesity – Obese men who are diagnosed with prostate cancer have more than two-and-a-half times the risk of dying from the disease as compared to men of normal weight. An earlier study found that obese men have an 80 percent higher risk of developing aggressive prostate cancer. Learn more >

Smoking – Middle-aged men who are long-term, heavy smokers face twice the risk of developing aggressive forms of prostate cancer than men who have never smoked, according to a study by Drs. Stanford, Thomas Vaughan and colleagues. Learn more >

Smokers, dairy and fatty foods – Research led by Dr. Neuhouser has found that current or former heavy smokers who ate more dairy foods had a 41 percent reduced risk of aggressive prostate cancer, compared to men in that category with lower dairy intake. On the other hand, smokers who followed diets rich in omega-6 fatty acids — found in large quantities in safflower, soybean and corn oils — faced a more than doubled risk of prostate cancer, but only if they had a family history of prostate cancer. Learn more >

Coffee – Stanford and colleagues found that men who drank four or more cups of coffee per day experienced a 59 percent reduced risk of prostate cancer recurrence and/or progression as compared to those who drank only one or fewer cups per week. Learn more >

Tea and risk reduction – Consuming 2 or more cups of  tea daily reduces the risk of developing prostate cancer, which is the most common form of cancer among men, according to findings from a study conducted by Drs. Stanford, Neuhouser and colleagues. The study, published in 2013, joins a growing body of research linking tea consumption to reduced prostate cancer risk.

Red wine – Men who drank four or more 4-ounce glasses of red wine per week experienced about a 60 percent lower incidence of the more aggressive types of prostate cancer. Learn more >

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Detection & Diagnosis

Fred Hutch researchers are at the forefront of improving how prostate cancer is detected and diagnosed, with the goal of identifying when the disease is truly lethal. Our findings include:

Improving existing detection methods – Measuring a man's prostate-specific antigen, or PSA, level is the most common test for early detection of prostate cancer, but studies have shown the method may detect tumors that would never require treatment while failing to find some aggressive cancers. Dr. Ruth Etzioni and colleagues were among the first to formally evaluate the test's ability to distinguish between true cancers and benign conditions. They have concluded that a variation on the PSA test that uses two types of PSA measurements could improve the test's accuracy for men with borderline-normal total PSA levels, potentially leading to a significant drop in medical costs and complications for this group of men.
Learn more >

Avoiding ‘overdiagnosis’ – Dr. Etzioni and her lab colleagues have also determined that roughly one-third of older men diagnosed with prostate cancer through the PSA test are "overdiagnosed" with the disease, meaning patients are receiving unnecessary surgeries or other treatments even though the disease isn't likely to threaten their health. Learn more >

Diagnosis and ethnicity – Dr. Etzioni and colleagues published the first study to document that frequency of prostate cancer testing is associated with a patient's race. They found that African-American men with prostate cancer are half as likely as Caucasian men to receive annual blood tests—called prostate-specific antigen, or PSA, tests—to monitor their disease. Learn more >

Identifying aggressive prostate cancer – Although most forms of prostate cancer are slow growing, the disease does have aggressive forms that can spread and become life-threatening. A significant portion of the Fred Hutch’s research in prostate cancer is dedicated to diagnosing aggressive forms the disease and identifying indicators of its presence or development. This work includes:

  • Biomarkers – Investigators may have discovered two urine-based biomarkers associated with prostate cancers that are likely to be aggressive and potentially life-threatening among men who choose to delay treatment after diagnosis in favor of a watchful approach. The results were produced by the Prostate Active Surveillance Study, a multicenter study coordinated by Hutchinson Center and lead by principal investigator Dr. Daniel Lin. Learn more >

  • Genetic variants - Dr. Janet Stanford and an international team of scientists have identified five inherited genetic variants strongly associated with aggressive, lethal prostate cancer. The discovery could lead to a simple blood test that would help determine which men should receive the most aggressive treatment options. Dr. Stanford, co-director of the Fred Hutch’s Program in Prostate Cancer Research, is planning additional studies with collaborators to better understand the research findings. Learn more >

  • DNA errors – Researchers have discovered recurrent genetic mistakes that are common to advanced prostate cancer that may contribute to disease progression. Dr. Peter Nelson, along with colleagues from the Hutch and University of Washington, also identified several instances of genetic “hypermutation” that could cause the cancer to become resistant to therapies commonly used to slow the progression of advanced prostate cancer. The discovery of these genetic mutations should provide clues that illuminate why some prostate cancers are lethal, and potentially could be used to develop screening tests for early detection or drug targets to slow or halt cancer growth. Learn more >

  • Finasteride – Dr. Mary Redmand and colleagues found that participants who took finasteride (Proscar), a common therapy for the treatment of enlarged prostate, had their high grade tumors detected earlier and at a less extensive stage. The research, conducted through the Prostate Cancer Prevention Trial, also discovered finasteride helped reduce the incidence of prostate cancer.

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Treatment & Prognosis

Fred Hutch is making key advances toward improving prostate cancer treatment and understanding how the disease spreads:

Coffee and tea delay prostate cancer progression – Bioactive compounds found in coffee and tea may delay the progression of prostate cancer, according to a study by Hutchinson Center investigators. The study, conducted by Drs. Neuhouser, Wright, Stanford and colleagues, suggests that regular coffee consumption is associated with a lower risk of prostate cancer recurrence and progression. However, no association was observed for tea consumption.

Ethnicity and treatment – A Hutch research team has found that African-American men with prostate cancer were 26 percent less likely to receive aggressive hormone treatment for early stage prostate cancer than their Caucasian peers. Learn more >

Long-term impact of prostate cancer treatments – A study that compared the long-term (15 years) impact of therapy on urinary, bowel and sexual function among men undergoing radical prostatectomy or external-beam radiation therapy found no significant relative differences in disease-specific functional outcomes. The study was conducted by Drs. Stanford, David Penson and collaborators from the Hutchinson Center and five other cancer centers.

Understanding progression – Dr. Valeri Vasioukhin and colleagues have uncovered a key driver behind the progression of prostate cancer—a discovery that could spawn new treatments to prevent the cancer's spread and improve survival rates. The researchers found that a protein called hepsin caused prostate-tumor cells to lose their grip from the surrounding tissue and spread from the prostate to bone, lung and liver. Learn more >

Understanding resistance to treatment – Drs. Peter Nelson and Elahe Mostaghel, along with colleagues at the University of Washington and Oregon Health Sciences University, uncovered what may be the key to understanding why prostate tumors eventually become resistant to androgen-deprivation, or hormone-withdrawal, therapy. Their findings could help lead to better treatments for cancer that has spread beyond the prostate to distant sites throughout the body, such as bone, lymph nodes and internal organs. Learn more >

Understanding side effects of treatment – Dr. Janet Stanford and colleagues have shown that survival rates are comparable for the two major treatments for prostate cancer—radiation and prostate-removal surgery. The research shows that radiation therapy is better for avoiding urinary incontinence and impotence, but surgery is better for avoiding complications of bowel function. This knowledge allows men to make treatment decisions based on quality-of-life concerns.

Dr. Stanford and colleagues also completed the first comprehensive study of sexual and urinary function among men who underwent radical prostatectomy—that is, surgery to remove the entire prostate—for early-stage cancer. The team found the impotence rate among these men was much higher than previously reported.

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