Meeting NewsPerspective

Calcium channel blockers may increase risk for pancreatic cancer

Photo of Zensheng Wang
Zhensheng Wang

Calcium channel blockers, specifically the short-acting form, appeared associated with increased risk for pancreatic cancer among postmenopausal women, according to a study presented at American Association for Cancer Research Annual Meeting.

“Pancreatic cancer is not very common in the United States. It is the 12th most common cancer, but it is a very lethal cancer, as [it is] the third leading cause of cancer death in the U.S.” Zhensheng Wang, PhD, postdoctoral associate at Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, said during a press conference. “The 5-year survival rate for pancreatic cancer is very poor at only 8.2%.”

Pancreatic cancer typically occurs among older individuals who also have chronic comorbid medical conditions, such as hypertension. Antihypertensive medication use has increased significantly among these individuals, Wang said.

Wang and colleagues used data from the Women’s Health Initiative to assess how antihypertensive drugs and the soluble receptor for advanced glycation end product (sRAGE) may affect pancreatic cancer risk.

The researchers collected data on medication usage from 145,551 postmenopausal women aged 50 to 79 years who were enrolled from 1993 to 1998 and did not have prevalent cancer at baseline. The investigators assessed four types of antihypertensive drugs: beta blockers, diuretics, angiotensin converting enzyme inhibitors and calcium channel blockers.

Mean follow-up was 13.8 years.

By August 2014, researchers observed 841 cases of pancreatic cancer.

Using an immunoassay, researchers assessed serum levels of sRAGE among 489 patients with pancreatic cancer and 977 noncancer controls.

After adjustment for comorbid factors, women who had ever used short-acting calcium channel blockers (n = 14,105) demonstrated a 66% higher risk for pancreatic cancer (HR = 1.66; 95% CI) compared with those who had ever used other antihypertensive drugs.

Those who used calcium channel blockers for more than 3 years demonstrated a 107% higher risk than those who had ever used other antihypertensive drugs. These association remained significant after investigators accounted for competing risks.

The other studied antihypertensive medications, including long-acting calcium channel blockers, did not appear associated with increased risk for pancreatic cancer.

Women who had ever used short-acting calcium channel blockers demonstrated significantly lower sRAGE levels compared with those who used any other antihypertensive medications (1,158 pg/mL vs. 1,446 pg/mL, P = 0.032).

sRAGE is thought to slow inflammatory response by blocking pro-inflammatory signaling. The blockage caused by the use of calcium channel blockers may reduce sRAGE release and cause chronic inflammation, a known risk factor for pancreatic cancer and other cancer types.

Limitations of the study included its observational nature, the inclusion of only postmenopausal women but no men or younger women, and several unmeasured potential confounding factors.

“Our findings on short-acting calcium channel blocker use and pancreatic cancer risk are novel and of potential broad medical and public health significance if confirmed,” Wang said in a press release. “Short-acting calcium channel blockers are still prescribed to manage hypertension, which is one of the components of metabolic syndrome, and metabolic syndrome is a possible risk factor for pancreatic cancer.” – by Cassie Homer

 

References:

Wang Z, et al. Abstract 4946. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.

Disclosures: The NCI and Houston VA Center for Innovations in Quality, Effectiveness and Safety funded this study. NIH and NHLBI fund the Women’s Health Initiative. Wang reports funding from the Cancer Prevention and Research Institute of Texas. Please see the abstract for all other authors’ relevant financial disclosures.

Photo of Zensheng Wang
Zhensheng Wang

Calcium channel blockers, specifically the short-acting form, appeared associated with increased risk for pancreatic cancer among postmenopausal women, according to a study presented at American Association for Cancer Research Annual Meeting.

“Pancreatic cancer is not very common in the United States. It is the 12th most common cancer, but it is a very lethal cancer, as [it is] the third leading cause of cancer death in the U.S.” Zhensheng Wang, PhD, postdoctoral associate at Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, said during a press conference. “The 5-year survival rate for pancreatic cancer is very poor at only 8.2%.”

Pancreatic cancer typically occurs among older individuals who also have chronic comorbid medical conditions, such as hypertension. Antihypertensive medication use has increased significantly among these individuals, Wang said.

Wang and colleagues used data from the Women’s Health Initiative to assess how antihypertensive drugs and the soluble receptor for advanced glycation end product (sRAGE) may affect pancreatic cancer risk.

The researchers collected data on medication usage from 145,551 postmenopausal women aged 50 to 79 years who were enrolled from 1993 to 1998 and did not have prevalent cancer at baseline. The investigators assessed four types of antihypertensive drugs: beta blockers, diuretics, angiotensin converting enzyme inhibitors and calcium channel blockers.

Mean follow-up was 13.8 years.

By August 2014, researchers observed 841 cases of pancreatic cancer.

Using an immunoassay, researchers assessed serum levels of sRAGE among 489 patients with pancreatic cancer and 977 noncancer controls.

After adjustment for comorbid factors, women who had ever used short-acting calcium channel blockers (n = 14,105) demonstrated a 66% higher risk for pancreatic cancer (HR = 1.66; 95% CI) compared with those who had ever used other antihypertensive drugs.

Those who used calcium channel blockers for more than 3 years demonstrated a 107% higher risk than those who had ever used other antihypertensive drugs. These association remained significant after investigators accounted for competing risks.

The other studied antihypertensive medications, including long-acting calcium channel blockers, did not appear associated with increased risk for pancreatic cancer.

Women who had ever used short-acting calcium channel blockers demonstrated significantly lower sRAGE levels compared with those who used any other antihypertensive medications (1,158 pg/mL vs. 1,446 pg/mL, P = 0.032).

sRAGE is thought to slow inflammatory response by blocking pro-inflammatory signaling. The blockage caused by the use of calcium channel blockers may reduce sRAGE release and cause chronic inflammation, a known risk factor for pancreatic cancer and other cancer types.

Limitations of the study included its observational nature, the inclusion of only postmenopausal women but no men or younger women, and several unmeasured potential confounding factors.

“Our findings on short-acting calcium channel blocker use and pancreatic cancer risk are novel and of potential broad medical and public health significance if confirmed,” Wang said in a press release. “Short-acting calcium channel blockers are still prescribed to manage hypertension, which is one of the components of metabolic syndrome, and metabolic syndrome is a possible risk factor for pancreatic cancer.” – by Cassie Homer

 

References:

Wang Z, et al. Abstract 4946. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.

Disclosures: The NCI and Houston VA Center for Innovations in Quality, Effectiveness and Safety funded this study. NIH and NHLBI fund the Women’s Health Initiative. Wang reports funding from the Cancer Prevention and Research Institute of Texas. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective
    Manish A. Shah

    Manish A. Shah

    This is a really interesting epidemiologic study that looked at antihypertensives and their association with cancer risk. Wang and colleagues discovered that short-acting calcium channel blockers were associated with a higher risk for pancreatic cancer — almost a twofold risk. The mechanism, the researchers postulated, was the down regulation of sRAGE, a receptor related to inflammation. In a previous study by another group 5 to 6 years ago published in Cancer Research, researchers suggested there is an inverse relationship between sRAGE serum levels and pancreatic cancer. In this large cohort study, they found that people who had lower sRAGE actually had a higher risk for pancreatic cancer.

    I think the study presented at AACR is compelling, not just because it was an observational study that showed this association, but it also actually supports previous work. There is a potential mechanism here that is really interesting. The other thing that is really interesting is they looked at four different classes of antihypertensives. Only calcium channel blockers were associated with a higher risk for pancreatic cancer, and that was because it modulates sRAGE. This appears not to be a random association, but a specific one related to short-acting calcium channel blockade.

    This study could have a significant impact on clinical practice because there are many different antihypertensives available. If you had an option of one of the others, I think you’re much more likely to choose one that doesn’t have the association with risk for pancreatic cancer. Clinicians should definitely keep these data in mind when they’re making a choice about what antihypertensives they’re prescribing.

    This study only included postmenopausal women. We don’t have any data on men or younger women to see if calcium channel blockers, or modulation of sRAGE, affects pancreatic cancer risk in those populations. Although it is possible, we would need to investigate the role sRAGE plays in inflammation relative to menopause and see if the mechanism can be translated to younger women or to men. Overall, the data are quite compelling.

    It’s also important to note the Women’s Health Initiative, which was the source of the data from this study, was supported by NIH. I think these kinds of studies, which allow us to have great resources, will have an incredible future impact. We should continue to support this kind of research.

    • Manish A. Shah, MD
    • Weill Cornell Medicine NewYork-Presbyterian

    Disclosures: Shah reports no relevant financial disclosures.

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