Low-Dose Aspirin Use May Lower Pancreatic Cancer Risk

Low-Dose Aspirin Use May Lower Pancreatic Cancer Risk

The National Cancer Institute projects that in 2014 there will be roughly 46,000 new cases and 40,000 deaths from pancreatic cancer, the 10th highest cancer in terms of new cases each year and the 4th highest in deaths per year. Pancreatic cancer has a five-year survival rate of less than 5% and a 2014 study predicts that by 2030 pancreatic cancer will be the second deadliest cancer in the United States. A functioning pancreas is composed of two different types of glands: exocrine glands that produce digestive juices to breakdown food and endocrine glands, which secrete the hormones insulin and glucagon that affect levels of sugar in the blood. According to the American Cancer Society, “It is very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have different signs and symptoms, are diagnosed using different tests, are treated in different ways, and have different outlooks.” Pancreatic cancer risk factors include smoking, a family history of pancreatic cancer, a family or personal history of chronic pancreatitis, history of diabetes mellitus, obesity, non-O blood type, and being of Jewish or African American ethnic origin. Pancreatic cancer can be challenging to detect and diagnose early due to a lack of apparent signs and symptoms in the early stages of the cancer.

Aspirin is a salicylate drug and a nonsteroidal anti-inflammatory drug (NSAID) that is effective by blocking a specific natural substance in the body that causes fever, pain, swelling, and blood clots. Aspirin is taken to reduce fevers and provide relief from mild or moderate pain from headaches, muscle aches, colds, and toothaches. Under the instruction of their doctor, low-dose aspirin is taken daily by many to prevent blood clots, lowering the risk of strokes and heart attacks and raising the odds of surviving one. Studies have suggested an association between aspirin use and reduced risk of breast, colorectal, esophageal, lung, ovarian, and stomach cancer.

The Study

In a 2014 study “Case-Control Study of Aspirin Use and Risk of Pancreatic Cancer” conducted by researchers at the Yale School of Public Health and published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, Samantha A. Streicher, PhD Candidate, Herbert Yu, MD, PhD, MSc, Lingeng Lu, MD, PhD, Mark S. Kidd, PhD, and Harvey A. Risch, MD, PhD, explored the association between aspirin use and pancreatic cancer risk. The study used data from the Connecticut Pancreas Cancer Case-Control Study. The study population included 362 cases of newly diagnosed individuals with pancreatic cancer recruited from 30 general hospitals in Connecticut from January 1, 2005 to August 31, 2009 and 690 randomly selected controls from Connecticut matched in terms of gender and age at the time of case recruitment.

The study focused on the association between risk of pancreatic cancer and the number of years since one started using aspirin, the number of years one used aspirin, and when one stopped using aspirin. This information was obtained from study subjects during interviews and separated into information on low-dose aspirin use (75 to 325 mg per day commonly taken for heart disease prevention) and regular dose aspirin use (>325 to 1,200 mg every 4 to 6 hours used for pain or anti-inflammation). The researchers also took into account potential confounding factors of: age at the time of the interview, adult BMI, gender, race/ethnicity, smoking history, history of diabetes mellitus diagnosed more than three years prior to the interview, education level, and ABO blood type.

The case study population consisted of: 57% men, 92% non-Hispanic white, 36% former smokers and 14% current/recent smokers who quit in the last 10 years, and 19% diagnosed with diabetes mellitus at least three years before the interview. In comparison to control subjects, case subjects were more likely to be current/recent smokers, have been diagnosed with diabetes mellitus more than three years prior to the interview, and were less educated. The study found that 96% of low-dose aspirin users and 92% of regular dose aspirin users reported taking aspirin on a daily basis.

For subjects continuing use of low-dose aspirin for ≤ 6 years, there was a 37% reduction in risk of pancreatic cancer and for > 10 years there was a 60% reduction in risk. Subjects who took low-dose aspirin for ≤ 3 years prior to study enrollment had a 48% reduction in risk, for > 7 to ≤ 10 years a 52% reduction in risk, and > 20 years a 61% reduction in risk. Reduction in risk of pancreatic cancer for subjects who regularly used low-dose aspirin ranged from a 43% reduction if regularly used for > 1 year to ≤ 3 years to a 61% reduction if used for > 20 years. Subjects who stopped continuing use of any aspirin within 2 years prior to study enrollment experienced a threefold increased risk for pancreatic cancer. Dr. Harvey Risch, a senior author of the study, remarked that overall the study found that “the use of low-dose aspirin was associated with cutting the risk of pancreatic cancer in half with some evidence that the longer low-dose aspirin was used, the lower the risk.”

Study Conclusions, Limitations, and Future Research

A problem with older studies exploring the association of aspirin use with a reduction in the risk for pancreatic cancer is that according to Dr. Risch, “Older studies of aspirin use have been clouded by the use of regular dose aspirin for pain relief from conditions that themselves might be related to the risk of pancreatic cancer.” In recent years, people have been using low-dose aspirin to prevent heart attacks and stroke for a long enough period of time to be able to examine a possible association with pancreatic cancer risk reduction. Thus, study authors called this study the first to explore the association between pancreatic cancer and years since aspirin use began and years since aspirin use ended and the first to examine the association between risk of pancreatic cancer and calendar time periods of aspirin use.

The study concluded that the results “provide further evidence that a daily aspirin regimen may afford chemoprophylaxis against pancreatic cancer,” or simply that a daily aspirin regimen may be taken as a chemical agent to prevent pancreatic cancer. Limitations were present in the study design in that aspirin use was classified based on type of aspirin instead of the reason for aspirin use, data was not recorded for reasons for aspirin use or frequency of use beyond daily use, and case-control studies like this one can be subject to selection and information bias.

Even though the study findings significantly show a reduction in risk of pancreatic cancer with continual low-dose aspirin use, the study researchers are unclear as to how aspirin works to reduce pancreatic cancer risk. Dr. Risch remarked that pancreatic cancer takes 10 to 15 years to develop so aspirin could be halting new tumor formation or aiding the immune system in defending against tumors. He hypothesized that the association could be because “aspirin has anti-inflammatory properties and if pancreatic cancer starts by low level chronic inflammation that causes some pancreas cells to lose genetic control and become cancerous, then aspirin’s effect on reducing inflammation would be beneficial.”

Dr. Risch noted that individuals are “more likely to quit” taking aspirin prior to pancreatic cancer diagnosis because of physiologic changes the disease can cause, including the emergence of taste disorders. Thus, going forward, future studies need to work on pinpointing patterns of aspirin use (currently using aspirin, quitting using aspirin, and longer duration of aspirin use) and the effect on the risk of pancreatic cancer. To strengthen and elaborate on this study’s conclusions, larger studies are needed to determine who should be taking aspirin, at what dosage, and for how long. The PanC4, the Pancreatic Cancer Case-Control Consortium, is currently working to pool analyses of studies to further explore the impacts of aspirin use.

Inconsistent Findings:

Studies exploring the association between aspirin use and pancreatic cancer risk reduction have been inconsistent in their findings of the beneficial effects of aspirin. Here are five studies published from 2002 to 2011 providing different insights on the impact of aspirin’s use on pancreatic cancer risk reduction.

  • A 2002 study, “Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer,” examined 28,283 postmenopausal women in Iowa from 1992 through 1999 to determine the association between aspirin use and incidence of pancreatic cancer. In the seven years of follow up, 80 cases of pancreatic cancer were observed in the study population. The study found “a trend of decreasing risk of pancreatic cancer incidence with increasing frequency of aspirin use per week.”
  • A 2002 hospital based case-control study, “Regular use of aspirin and pancreatic cancer risk,” used a study population of 194 pancreatic cancer patients and 582 age and sex matched control patients  all treated at Roswell Park Cancer Institute to explore the association between pancreatic cancer risk and aspirin use. The study found that “pancreatic cancer risk in aspirin users was not changed relative to non-users.”
  • In 2003, a study “A Prospective Study of Aspirin Use and the Risk of Pancreatic Cancer in Women,” explored the association between aspirin use and pancreatic cancer development. The study population consisted of 88,378 women without cancer at the beginning of the study and in 18 years of follow up observed 161 cases of pancreatic cancer. Aspirin use was first recorded at the beginning of the study in 1980 and then updated every two years. The study found that “extended periods of regular aspirin use appear to be associated with a statistically significantly increased risk of pancreatic cancer among women.”
  • In 2010, a hospital based case-control study “Aspirin use and pancreatic cancer risk,” was led in Italy from 1991 to 2008 examining 308 patients with pancreatic cancer and 477 patients at the same hospital that did not have conditions related to risk factors for pancreatic cancer. The study found no association between consistent aspirin use and reduction of pancreatic cancer risk, noting that the results did suggest “a possible protective effect for long term current users.”

What It All Means

According to Dr. Risch this study, “Case-Control Study of Aspirin Use and Risk of Pancreatic Cancer” provides evidence that “people who are considering aspirin use to reduce the risk for cardiovascular disease can feel positive that their use might also lower their risk for pancreatic cancer and quite certainly wouldn’t raise it.” However, aspirin has its own potential risks and side effects, including bleeding and stomach ulcers, and should not be taken without first consulting a doctor. Dr. Risch believes that a small group of individuals who have “strong” family histories of pancreatic cancer or have used genetic testing to determine that they are at an increased risk for pancreatic cancer should talk with their doctor about using aspirin as part of a regimen to lower their risk for pancreatic cancer. While this study’s findings suggest that aspirin use reduces the risk of pancreatic cancer, currently all that is known is that according to Dr. Risch “empirically aspirin seems to do something” but it has not been conclusively proven that aspirin use decreases pancreatic cancer risk. For a cancer that will affect roughly 1 in 60 adults with the worst five-year survival rate of all cancers, hopefully future research will provide definitive evidence for ways to reduce pancreatic cancer risk.

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