Office of Research & Development

VA research on

Cancer


Introduction

Cancer is a general term that includes more than 200 different diseases. In all forms of cancer, cells in the body grow and multiply abnormally, eventually taking over and destroying normal tissue.

The main types of cancer are leukemias and lymphomas, involving the blood and related tissues; carcinomas, which occur in the skin, glands, and certain organs; and sarcomas, which involve muscles and connective tissue.

VA researchers have long been interested in the causes of cancers, in finding new treatments for different forms of cancer, and in evaluating existing treatments. In 1930, the year the Veterans Administration (the predecessor to today's Department of Veterans Affairs) was established, the Hines, Illinois, VA hospital created a cancer treatment center, in which surgeons, radiologists, and specialists worked together to provide the latest treatments for cancer patients.

A 2012 VA study reported that around 40,000 cancer cases are reported to VA's Central Cancer Registry annually, about three percent of all cancers in the United States.

The five most frequently diagnosed cancers among VA cancer patients were prostate, lung and bronchial, colorectal, urinary and bladder cancers, and skin melanomas. This list is similar to that for American men as a whole.

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Selected Major Accomplishments

  • 1932: Established tumor research laboratory in Hines, Illinois—the first VA research laboratory to receive funding specifically for research
  • 1950: Concluded, in a paper by Dr. Robert Schrek of Hines, there is "strong circumstantial evidence" linking cigarette smoking with respiratory tract cancers
  • 1956: Linked cigarette smoking with precancerous lesions
  • 1984: Developed a transdermal nicotine patch to reduce the cravings for cigarettes
  • 2000: Showed the superiority of colonoscopy to sigmoidoscopy
  • 2012: Demonstrated that observation is as effective as surgery in treating early-stage prostate cancer
  • 2015: Joined with gastroenterologists from throughout the United States, Canada, and the United Kingdom to develop a new set of recommendations on the surveillance and management of areas of pre-cancerous cells in patients with inflammatory bowel disease

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New, Ongoing, and Published Research

VA researchers conduct laboratory experiments aimed at discovering the molecular and genetic mechanisms involved in cancer; studies looking at the causes of disease; clinical trials to evaluate new or existing treatments; and studies focused on improving end-of-life care.

Investigators are focusing on discovering the sources of cancer cells in the body and ways to eradicate them; evaluating new and existing treatments; and looking at ways to improve end-of-life cancer care for those with terminal diagnoses. Among other goals, VA researchers are finding ways to maintain good health and enhance the quality of life of the increasing number of cancer survivors.

➤ Smoking and cancer

Early pioneers—In 1932, the Hines VA hospital established a Tumor Research Laboratory to complement the work of its cancer treatment center—VA's first laboratory to receive funds specifically for research work.

The laboratory's first success came through the work of Dr. Robert Schrek, who was among the first researchers to look at the effects of radiation on cancer cells. Schrek also did pioneering studies on how skin cancers developed, and on the effects of cigarette smoking on cancers of the lung, larynx, and pharynx.

Schrek's work was followed up by the work of Dr. Oscar Auerbach, of VA's East Orange hospital, now the East Orange campus of the VA New Jersey Health Care System. Auerbach's landmark animal research study found that smoking for three years caused major changes in the lungs of animals who were taught to inhale cigarettes—and that many developed cancer.

Auerbach was later a participant in the first Surgeon General's report, published in 1964, which explained the harmful effects of smoking to America and the world.

Nicotine patch—In 1984, VA Research made a major contribution toward helping Veterans quit smoking through the development of the nicotine patch. The patch was developed by Drs. Jed Rose, Daniel Rose (Jed Rose's brother), and Murray Jarvik, The patch, which Jed Rose first tested on himself, transfers nicotine into the bloodstream to reduce cravings for the substance.

Testing e-cigarettes—In 2015, a team of VA researchers at the VA San Diego Healthcare System looked at the possible health risks of electronic cigarettes, and found they damaged cells in ways that could lead to cancer. The damage occurred even with nicotine-free versions of the products.

The lab experiments did not find that e-cigarette vapor was as harmful to cells as cigarette smoke, but because similar cell-damage mechanisms were observed as the result of both e-vapor and regular cigarette smoke, the researchers asserted that e-cigarettes are not necessarily a healthier alternative to smoking regular cigarettes.

The team concluded that further research is needed to better understand the long-term health effects of e-cigarettes in humans.

A 2016 study by a different team of researchers in San Diego reported that e-cigarettes can kill human airway cells. At high doses, they also suppress users' immune defenses, inflame the lungs, and promote the growth of bacteria in the lungs that can cause pneumonia and other diseases.

The team found these issues in the airways and blood of mice that inhaled e-cigarettes for one hour a day, five days a week, for four weeks. According to researcher Dr. Laura Crotty Alexander, the study demonstrates that the vapor from e-cigarettes is not benign. She described the findings as "frightening" for those who use the product.

Lung-cancer screening—Another 2015 study, by researchers with the VA Puget Sound Health Care System and the University of Seattle, found that lung cancer screening can lower smokers' motivation to quit smoking.

The team studied 37 current smokers who were offered lung cancer screening by their primary care physician during 2014. After the screening, the smokers were interviewed by the research team. The team found that nearly half of those interviewed found some reason to believe that just being screened meant that they did not need to stop smoking.

Some told the researchers that undergoing the test had the same benefit as stopping smoking, even when precancerous lung nodules were found. Others felt that being able to return for additional screenings would protect them, and still others felt that a cancer-free screening test indicated that they were among the lucky ones who would avoid the harms of smoking.

All of these assumptions are false—as is the assumption many study participants had that lung cancer was the only potentially lethal effect of smoking. The team suggested that counseling for smokers should target these and other rationalizations some people use to avoid quitting.

Precision oncology for lung cancer—Also in 2015, VA's New England Healthcare System and the Massachusetts Veterans Epidemiology Research and Information Center instituted a clinical program to help Veterans who have been newly diagnosed with non-small cell lung center.

As Veterans are diagnosed, VA physicians will take a specimen of their tumor and send it to qualified laboratories for targeted genomic sequencing, a process that determines the DNA sequence of genes that are considered important in lung cancer.

The sequencing will identify specific mutations, or changes, that are causing the Veteran's lung cancer to grow, allowing the Veterans to benefit from drugs that are targeted to those mutations, and to take part in clinical trials of new drugs targeted toward their specific mutations.

This precision oncology program is currently underway at VA facilities throughout New England, and VA hopes to expand it nationally in the future.

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➤ Prostate cancer

Because VA has established a relationship between exposure to Agent Orange or other herbicides during military service and prostate cancer, VA researchers have worked hard to find additional information about this particular form of cancer.

PIVOT trial—In 2012, VA's Prostate Cancer Intervention Versus Observation (PIVOT) Trial, conducted by VA's Cooperative Studies Program, found no difference in survival between men with early-stage prostate cancer who had their prostate surgically removed and those who were simply watched by their doctors, and were only treated as needed to address symptoms if they occurred.

Surgery vs. radiation—In 2013, another trial, this one funded by the National Cancer Institute and involving VA investigators, found that surgery and radiation treatments for prostate cancer both have serious side effects, and that differences in side effects between the two kinds of treatments even out by 15 years after surgery.

Gene therapy—Another 2013 study, based at the Kansas City (Missouri) VA Medical Center, found that a combination of genes for prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA) seems to stop prostate tumors from growing in mice. When this combination was given to mice with prostate tumors, the mice churned out cells (antigen-specific T cells) that attacked the tumor cells—and 80 percent of the mice became tumor-free.

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➤ Colon cancer

One of VA's important cancer research objectives in treating cancer is improving doctors' ability to diagnose colon cancer—a disease that affects about 150,000 Americans each year. Colon cancer can be cured if diagnosed early, yet one-third of patients who develop colon cancer will die from the disease.

Seminal colonoscopy study—VA Cooperative Study 380, the results of which were published in 2000, found that colonoscopic screenings (in which a long, flexible, tubular instrument is used to visually inspect the entire colon) could detect abnormal growths called neoplasms better than sigmoidoscopy (a flexible instrument that inspects only the lower colon).

Detecting flat growths—A 2008 study by researchers at the VA Palo Alto Health Care System found that while doctors use colonoscopy to find abnormal growths, called polyps, which protrude from the lining of the colon, difficult-to-detect flat abnormal growths are more common in U.S. patients than was previously thought. These flat growths are much more likely to be cancerous than are polyps.

Virtual colonoscopy—In another study, published in 2012, researchers found that virtual colonoscopy is as accurate as conventional colonoscopy in finding potentially cancerous polyps. Virtual colonoscopy is a less invasive form of colonoscopy in which physicians use CT scanners to hunt for cancers and polyps.

Patients undergoing virtual colonoscopies do not need to use laxatives before the procedure, often viewed as the most difficult aspect of a colonoscopy.

Colonoscopy withdrawal time—A 2015 study led by researchers with the Minneapolis VA Health Care System and the University of Minnesota found that longer-lasting colonoscopies are associated with lower cancer rates. The team looked at nearly 77,000 screening colonoscopies, and found that those patients who had been examined by doctors with withdrawal times shorter than six minutes, on average, were more likely to have cancer.

Contributing to guidelines—In 2015 VA researchers from three sites joined with gastroenterologists from throughout the United States, Canada, and the United Kingdom to develop a new set of recommendations on the surveillance and management of areas of pre-cancerous cells in patients with inflammatory bowel disease.

The new guidelines focus less on random biopsies to find potential trouble spots and more on using newly available technologies to identify and remove these pre-cancerous areas before cancer can develop.

DNA stool test—In 2014 researchers at the Richard A. Roudebush VA Medical Center in Indianapolis and the Indiana University School of Medicine published the results of a 90 site study to evaluate a new DNA test to determine whether colon cancer is present. (DNA is a substance that carries genetic information in the cells of plants and animals, including humans.)

The research team found that the test, which evaluates the DNA found in people's stool, detects significantly more cancers than the currently available stool evaluation test, called the fecal immunochemical test. However, it does so at the cost of more false-positive results.

The U.S. Food and Drug Administration approved the screening test, called Cologuard, in August 2014, and it is now available with a doctor's prescription.

CONFIRM trial—At present, VA is conducting a trial (Cooperative Study 577), involving more than 50,000 Veterans, that will compare the long-term health effects of colonoscopy screenings versus fecal occult blood testing, a simple test in which a small plastic device is used to sample feces. The sample is then checked in the lab for signs of human blood.

Enrolled Veterans will either receive a one-time colonoscopy or an annual FIT test for 10 years. If the FIT test is positive, a follow-up colonoscopy will be recommended. The trial is currently recruiting participants.

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➤ Testicular and stomach cancer

Testicular cancer typically develops in one or both testicles in young men, but it can occur in older men as well. It is a highly treatable and usually curable form of cancer.

Treatment options for testicular cancer typically focus on chemotherapy, surgery, or radiation therapy, which involves treating the cancer by means of X-rays or radioactive substance. Radiation is less often used to treat testicular cancer than it was in the past, and when it is used, it is much more targeted and involves lower radiation doses than previously.

An international study completed in 2015, involving researchers from the Oklahoma City VA Medical Center, looked at more than 22,000 men who were diagnosed with testicular cancer between 1959 and 1987, when radiation doses were higher and less targeted.

The team found that those who had received any level of radiation therapy had nearly six times the risk of developing stomach cancer, compared with those who had not had any radiation at all. Those who received very high doses of radiation were at 20 times the risk. The team hopes that their findings will get clinicians to look quickly for the possibility of stomach cancer in patients who have been treated for testicular cancer with gastrointestinal problems, and will help doctors better weigh the risk of using radiation to treat new patients with testicular cancer.

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➤ Breast cancer

While most of the patients VA treats are male, the department is seeing increasing numbers of woman Veterans. VA researchers are therefore looking closely at breast cancer, its causes, and treatments for the disease.

A 2015 study, conducted at the Kansas City (Missouri) VA Medical Center, found that low-dose aspirin can impair the ability of breast cancer cells to renew themselves.

The team tested breast cancer cells in mouse models, and found that a daily dose of low-dose aspirin almost halved tumor growth in the mice's tumors by altering the molecular signature in breast cancer cells—and those cells it failed to kill were unable to grow.

The researchers believe that daily doses of low-dose aspirin would be effective both for patients after chemotherapy, and as a preventative measure.

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More on Our Website

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Selected Scientific Articles by Our Researchers

Historical

Tobacco Smoking as an etiologic factor in disease; cancer. Schrek R, Baker LA, et al. VA's first major study linking smoking to cancer. Cancer Res. 1950 Jan; 10(1):49-58.

The effect of direct cigarette smoke inhalation on the respiratory tree of dogs. Auerbach O, Hammond, EC, Kirman D, Garfinkel L, Stout AP. Auerbach's seminal paper on the effects of smoking. Natl Cancer Inst Monogr 1968 Jun;28:65-67

Transdermal administration of nicotine. Rose JE, Jarvik ME, Rose KD. A paper describing the value of the nicotine patch. Drug Alcohol Depend. 1984 May;13(3):209-13

Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. VA study demonstrating the value of colonoscopies compared to sigmoidoscopy. N Engl J Med 2000 Jul 20.

The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer. Wilt TJ. Baseline information on VA's PIVOT trial. J Natl Cancer Inst Monogr, 2012 Dec; 2012(45):184-90

Recent

Multitarget stool DNA testing for colorectal-cancer screening. Imperiale TF, Ransohoff, DF, Itzkowitz S, Levin, TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. A stool test combining altered human DNA and fecal hemoglobin showed higher single-application sensitivity than a commercial FIT for both colorectal cancer and advanced precancerous lesions, although with lower specificity.

NEJM March 19, 2014/NEJMoa1311194

Editorial: Stool DNA and colorectal-cancer screening. Robertson DJ, Dominitz JA. Only through a better understanding of other key factors, such as the screening interval, adherence, cost, and diagnostic evaluation of positive results, can we determine the appropriate place for stool DNA testing on the screening menu. NEJM March 19, 2014/NEJMe1400092

Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis. Deppen SA, Blume JD, Kensinger CD, Morgan AM, Aldrich MC, Massion PP, Walker RC, McPheeters ML, Putnam JB Jr., Grogan EL. FDG-PET scans were 16 percent more likely to give a false-positive result when patients lived in regions in which infectious lung disease is prevalent. JAMA 2014 Sep 24;312(12):1227-36.

Increased stomach cancer risk following radiotherapy for testicular cancer, Hauptmann M, Fossa SD, Stovall M, van Leeuwen FE, Johannesen TB, Rajaraman P, Gilbert ES, Smith SA, Weathers RE, Aleman BM, Andersson M, Curtis RE, Dores GM, Fraumeni JF, Hall P, Holowaty EJ, Joensuu H, Kaijser M, Kleinerman RA, Langmark F, Lynch CF, Pukkala E, Storm HH, Vaalavirta L, van den Belt-Dusebout AW, Travis LB, Morton LM. Abdominal radiotherapy for testicular cancer increases the risk for stomach cancer. Br J Cancer, 2015 Jan 6;112(1):44-51.

miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the epigenetic modifier DNMT1. Lombard AP, Moose BA, Libertine SJ, Lim M, Nakagawa RM, Vidal KD, Costanzo NC, Ghost PM, Muddy M. The MicroRNA miR-148a is a tumor suppressor in urothelial cell carcinoma of the bladder. Mol Carcinog. 2015 Apr 11.

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition. Malty G, De A, Das A, Banerjee S, Sarkar S, Banerjee SK. Aspirin not only prevents breast tumor cell growth in vitro and tumor growth in nude mice models, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells and delays the formation of a palpable tumor. Lab Invest. 2015 Jul;95(7):702-17.

A population-based study of men with low-volume low-risk prostate cancer: does African-American race predict for more aggressive disease? Schreiber D, Chhabra A, Rineer J, Weedon J, Schwartz D. Data supports continued use of active surveillance for prostate cancer in African Americans. Clin Genitourin Cancer. 2015 Aug; 13(4):e259-64.

Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor. Singh T, Gupta NA, Xu S, Prasad R, Velu SE, Katiyar SK. The chemotherapeutic effect of honokiol against head and neck squamous cell carcinoma is better than gifitinib, a commonly used drug for treating this cancer. Oncotarget. 2015 Aug 28;6(25):21268-82.

Attitudes and perceptions about smoking cessation in the context of lung cancer screening. Zeliadt SB, Heffner JL, Sayre G, Klein DE, Simons C, Williams J, Reinke LF, Au DH. Health care professionals should be aware that the opportunity for early detection of lung cancer may be interpreted as a way of avoiding the harms of smoking. JAMA Intern Med. 2015 Sep;175(9):1530-7.

Longer withdrawal time is associated with a reduced incidence of interval cancer after screening colonoscopy. Shaukat A, Rector TS, Church TR, Lederle FA, Kim AS, Rank JM, Allen JI. Shorter mean annual withdrawal times during screening colonoscopy were independently associated with lower adenoma detection rates and increased risk of interval colorectal cancer. Gastroenterology. 2015 Oct;149(4):952-7.

Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Yu V, Rahimy M, Korrapati A, Xuan Y, Zou AE, Krishnan AR, Tsui T, Aguilera JA, Advani S, Crotty Alexander LE, Brumund KT, Wang-Rodriguez J, Ongkeko WM. E-cigarette vapor, both with or without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed. Oral Oncol. 2016 Jan;52:58-65.

Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. Hwang JH, Lyes M, Sladewski K, Enany S, McEachern E, Mathew DP, Dae S, Moshensky A, Bapat S, Pride DT, Ongkeko WM, Crotty Alexander LE. E-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria. J Mol Med (Berl). 2016 Jan 25. (Epub ahead of print.)

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Cancer Fact Sheet


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VA Research in the News

Regenstrief study finds natural language processing accurately tracks colonoscopy quality, Indiana University School of Medicine Newsroom, March 10, 2015

Lymphomas tied to metabolic disruption, University of Texas news release, July 16, 2015

Lung screening may not push smokers to quit, The New York Times, Sept. 7, 2015

UCLA, VA team up to improve cancer care for Veterans, Los Angeles Daily News, Sept. 30, 2015

E-cigarettes damage cells in ways that could lead to cancer, Medical News, Dec. 29, 2015

Gene thought to suppress cancer may actually promote spread of colon cancer, University of Missouri School of Medicine news release, Jan. 4, 2016

Veteran blood bank may play key role in cancer 'moon shot', Military.com, Jan. 19, 2016

E-cigarette vapor boosts superbugs and dampens immune system, San Diego Health news release, Jan. 26, 2016

VA and other U.S. Government Online Resources

Quality of Care: Cancer, Department of Veterans Affairs
Do You Know the Risk Factors for Breast Cancer? Department of Veterans Affairs news feature

Prostate Cancer and Agent Orange, Department of Veterans Affairs

Health Awareness Campaigns: Breast Cancer, Department of Veterans Affairs

Quit Tobacco, Department of Veterans Affairs

Tobacco and Health, Department of Veterans Affairs

Comprehensive Cancer Information, National Cancer Institute (Spanish version here)

Cancer Prevention and Control, Centers for Disease Control and Prevention

Smokefree.gov


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