Scientists are searching aggressively for a link between diabetes and cancer; more than a dozen studies have been published in the past 3 years. While most explored the relationships between type II diabetes and pancreatic cancer, the studies also found associations between diabetes and non-Hodgkin’s lymphoma, and colorectal, prostate, endometrial, liver, breast, and renal cell cancers.
The strongest hypothesis to explain why diabetes might increase the risk for certain cancers revolves around hyperinsulinemia, the high blood levels of insulin characteristic of diabetes. “From animal studies we know that high insulin levels can directly promote tumor growth,” said Frank Hu, M.D., assistant professor of nutrition at the Harvard University School of Public Health, Boston.
Hu and colleagues concluded in a 1999 paper, based on data from the Nurses’ Health Study, that diabetes conferred an increased risk of colorectal cancer in women. Patients with diabetes were 1.43 times more likely to get colorectal cancer, and 2.39 times as likely to die of colorectal cancer.
Some studies have been troubled by the chicken-and-egg phenomenon—did the cancer alter the workings of the body such that diabetes resulted, or did the diabetes eventually lead to cancer? In the Nurses’ Health Study, Hu said, the temporal relationship was clear: “The women had diabetes first, for sure, and later they got colon cancer.”
High insulin levels have been shown in animals to stimulate IGF-1, which has been shown to increase the risk of colorectal cancer, Hu said. It may be that diabetes and colorectal cancer could share several of the same environmental risk factors, such as obesity, sedentary behavior, and a high-sugar diet. “It may be that because of the sharing of environmental factors, people may develop both [cancer and diabetes],” Hu said. After adjusting for these factors, however, he found that the increased risk persisted.
Other studies have found links between diabetes and colon cancer. A 1997 report found that diabetes was associated with an increased risk of colorectal cancer in people diagnosed with diabetes after age 40. The association was stronger in people diagnosed with diabetes at least 10 years before cancer diagnosis, and in those aged 60 and older at the time of cancer diagnosis. Adjustments for sex, education, body mass index, physical activity, energy intake, alcohol drinking and fiber intake did not modify the association. The researchers suggest that IGF-1 is involved in this process, as a promoter of colon tumor cell growth.
A 1998 study on diabetes and colorectal cancer found a modest association in men, but not women. Julie Will, Ph.D., an epidemiologist at the Centers for Disease Control and Prevention, Atlanta, used data from the 13-year Cancer Prevention Study, which involved more than 1 million respondents. She took on the topic because “it seemed there weren’t many really good prospective studies looking at diabetes and cancer, and I saw an opportunity to examine it in this large database.”
Will also published a 1999 study on diabetes and prostate cancer, using the Cancer Prevention Study data. That analysis found a slightly increased risk for prostate cancer in men who had diabetes for 5 or more years, compared with men without diabetes. Will plans to continue examining diabetes as a cancer risk factor, with future studies possible in breast and endometrial cancers.
A Link to Pancreatic Cancer
Pancreatic cancer is the most common subject of studies on diabetes as a risk factor; because both pancreatic cancer and diabetes involve the same organ, teasing out cause-and-effect scenarios is complicated. “There’s an interesting reciprocal relationship,” said Hu. “Those with pancreatic cancer are more likely to get diabetes—diabetes is just a consequence of pancreatic cancer because the beta cells are damaged.”
But is diabetes a risk factor for pancreatic cancer? A 1997 Danish study found that diabetes came first. A 1998 study from the American Cancer Society found a small but persistent increased risk of death from pancreatic cancer in diabetics, and concluded that diabetes may be a true, but modest, risk factor for pancreatic cancer. The next year, a study from the National Cancer Institute showed a 50% increased risk of pancreatic cancer in patients diagnosed with diabetes at least 10 years prior to a cancer diagnosis.
However, the NCI study indicated that diabetes may also be a complication of pancreatic cancer, a finding echoed by findings in Italy and Minnesota. The latter study found that a “recent diagnosis of [diabetes] may be the best clue” to diagnosing pancreatic cancer.
Diabetes’ association with other types of cancer is also murky. An Italian study showed that in women over 40, diabetes was associated with three times the risk of endometrial cancer, compared with women who did not have diabetes. Other research has found that the diabetes/endometrial cancer relationship is rooted in obesity, in that only obese women with diabetes have an additional risk of endometrial cancer.
Studies on liver cancer have been sparse, but a 1997 study out of Italy found that patients with types I and II diabetes had twice the risk of liver cancer, after adjusting for age, sex, area of residence, alcohol and tobacco consumption, history of hepatitis and cirrhosis, body mass index, and history of liver cancer in first-degree relatives. According to this research, a history of diabetes explains about 8 percent of cases of liver cancer in the population studied.
Although relationships have also been found between diabetes and breast cancer in postmenopausal women and between diabetes and renal cell cancer incidence and mortality, as of yet, no clear connection has been established between diabetes and any cancer type.
“It’s an interesting topic, especially in light of the fact that diabetes and obesity are increasing dramatically in this country,” Hu said. In an analysis of unpublished data, he found that overall, diabetes increases cancer mortality. “It looks as if the association is real.”
- Oxford University
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