Low levels of the obesity-related hormone adiponectin are associated with an increased risk of pancreatic cancer, researchers reported.
In a case-control study, pancreatic cancer patients had significantly lower levels of the hormone than controls in blood samples drawn at least a year before their diagnosis, according to Ying Bao, MD, ScD, of Harvard Medical School in Boston, and colleagues.
The association was independent of smoking, diabetes, body mass index, and other known or suspected risk factors for pancreatic cancer, Bao and colleagues reported online in the Journal of the National Cancer Institute.
The findings “provide additional evidence for a biological link between obesity, insulin resistance, and pancreatic cancer risk and also suggest an independent role of adiponectin,” they concluded.
The etiology of pancreatic cancer - the fourth leading cause of cancer death in the U.S. – is not well understood, the researchers noted. However, they added, evidence is growing that obesity is an important risk factor, suggesting that adiponectin, secreted primarily by adipose tissue, might also play a role.
To investigate, they turned to five large, long-running prospective cohorts, the Health Professionals Follow-up Study, the Nurses’ Health Study, the Physicians’ Health Study, the Women’s Health Initiative, and the Women’s Health Study.
Among the nearly 360,000 participants, they found 468 people who had developed pancreatic cancer, had given a blood sample more than year before the diagnosis, and had not had any other cancer, aside from nonmelanoma skin cancer.
The researchers also randomly selected 1,080 controls, who were matched by cohort, age, smoking and fasting status, and month of blood draw.
Analysis showed that median plasma adiponectin was 6.2 mcg per mL in patients and 6.8 in controls, a difference that was significant at P=0.009.
Plasma adiponectin was also inversely associated with cancer risk, consistently across the five prospective cohorts and independently of markers of insulin resistance, such as diabetes.
When adiponectin was divided into quintiles, higher levels were associated with a lower risk of cancer. Specifically, compared with the lowest quintile:
Participants in the second quintile had an odds ratio for cancer of 0.61, with a 95% confidence interval from 0.43 to 0.86.
Those in the third had an odds ratio of 0.58, with a 95% confidence interval from 0.41 to 0.84.
Those in the fourth group had an odds ratio of 0.59, with a 95% confidence interval from 0.40 to 0.87.
Those with the highest levels had an odds ratio of 0.66, with a 95% confidence interval from 0.44 to 0.97.
The trend was significant at P=0.04.
The study was carefully done but the exact role of adiponectin remains “unclear,” commented Jianliang Zhang, PhD, and Steven Hochwald, MD, both of the Roswell Park Cancer Institute in Buffalo, N.Y.
In an accompanying editorial, they concurred that the study establishes a link between adiponectin and pancreatic cancer risk, but added that it remains important to determine the exact interplay between the hormone and the malignancy.
The study opens the door to that research, they argued, with the potential of using the hormone both as a diagnostic marker and a therapeutic target.
“Early detection by the assessment of adiponectin has the potential to improve the survival rates of pancreatic tumor patients,” Zhang and Hochwald wrote.
“It is also inviting to speculate that therapeutic interventions to increase the levels of circulating adiponectin may prevent the development of pancreatic cancer and/or improve the survival of patients with malignancy,” they wrote.
The research had support from the National Cancer Institute, the NIH, the National Heart, Lung, and Blood Institute, the American Society of Clinical Oncology, the Howard Hughes Medical Institute, the Lustgarten Foundation, and the Conquer Cancer Coalition of Massachusetts.
The authors did not report potential conflicts.
The editorial authors did not report potential conflicts.
Primary source: Journal of the National Cancer Institute
Source reference: Bao Y, et al “A prospective study of plasma adiponectin and pancreatic cancer risk in five us cohorts” J Natl Cancer Inst 2012; DOI: 10.1093/jnci/djs474.