Individuals with type 2 diabetes mellitus (T2DM) are at increased risk for a number of cancers, but older men with T2DM have a reduced risk of prostate cancer (PCa), according to a retrospective, population-based cohort study.

At least 3 years after a T2DM diagnosis, men aged 65–74 years had a 27% decreased risk of PCa compared with non-diabetic men, researchers led by Diego Serraino, MD, of the Epidemiology and Biostatistics Unit, IRCCS CRO National Cancer Institute, Aviano, Italy, reported in Cancer Epidemiology (2016;41:80-87). The reason for this inverse relationship may be the reduced androgen levels among diabetics, the researchers said. They pointed out, however, that the mechanisms underlying this association remain unclear.

In contrast, among individuals with T2DM for 3 or more years, the risk of colorectal, lung, pancreatic, kidney, and bladder cancer was 56%, 37%, 55%, 43%, and 30% higher, respectively, compared with non-diabetic subjects. The risk of liver cancer was 2.6 times higher. Women with T2DM had a 24% increased risk of breast cancer.

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The study included 32,247 T2DM patients (17,827 men, 14,420 women) and 1,018,518 people without diabetes in northeastern Italy. Serraino’s group obtained data from administrative health-related databases covering the entire population living in the Friuli Venezia Giulia region in northeastern Italy. The median duration of follow-up was 3.65 years. The investigators documented 2,069 cancer cases (6.4%) among the 32,247 T2DM patients during the study period.

For the T2DM group overall (regardless of the time elapsed since T2DM diagnosis), the risk of cancer at any site was 28% higher and the risks of bladder and kidney cancer were 36% and 47% higher, respectively, compared with individuals who did not have T2DM. The risk of pancreatic cancer was 2.6 times higher.

The investigators noted that previous studies support a relationship between diabetes and the risk of kidney and bladder cancer, “making our results comparable with existing epidemiological evidence.”

The study found sex differences in the risk of various cancers. For example, among patients with T2DM for 3 years or more, men had a 47% increased risk of bladder cancer whereas women had a 31% decreased risk. In the T2DM group overall, the risk of pancreatic cancer was 3-fold higher among women versus 2-fold higher among men.

Among the T2DM patients, the overall probability of surviving 5 years after diagnosis of T2DM was 88.7%. With respect to the impact of T2DM on cancer survival, the researchers observed no differences in survival probabilities for prostate, colorectal, liver, pancreatic, and bladder cancers.

“Considering the high prevalence of T2DM in Italy, even a small increase in cancer risk could have severe consequences at a population level,” the authors concluded. “Therefore, specific primary and secondary cancer prevention programs are a priority among T2DM patients.”

Strengths of the study include its large study population and the use of a database covering the entire population in their region of interest, thus eliminating selection bias, the researchers noted.

The authors also acknowledged study limitations, including a lack of information on potentially confounding variables such as body mass index, obesity status, and smoking, as well as clinical information.