The connection between the type of antidiabetic therapy and pancreatic cancer

In the U.S., pancreatic cancer (PCa) ranks fourth in the structure of mortality from cancer in both men and women. Established risk factors for prostate cancer are smoking, obesity and family history of disease. The link between type two diabetes (T2D) and prostate cancer are more complex. On the one hand, type two diabetes may develop as a result of prostate cancer. On the other hand, accumulating evidence that type two diabetes plays an important role in carcinogenesis of this cancer pathology. For information on the connection type antidiabetic therapies with prostate cancer are almost absent. In this regard, researchers Anderson Cancer Center (MDAnderson Cancer Center) University of Texas conducted a case-control study based on a large hospital database methods and progress in the study.

Investigation of the center began in 2004 in order to elucidate the role of environmental and genetic factors in the development of prostate cancer. For this analysis, as "cases" included all patients with newly diagnosed in 2004-2008. And confirmed morphologically ductal adenocarcinoma of the pancreas. Appropriate for age, sex and race "controls" were recruited among healthy individuals are usually close, but not by blood, relatives or friends of patients at the center about oncopathology not the gastrointestinal tract and are not associated with smoking. "Control" had no genetic connection with "cases." All participants had not previously suffered from oncopathology.

Qualified staff collected the required information using a structured questionnaire and valid. Recorded demographic data, the presence of known risk factors for prostate cancer, type two diabetes (including age and year of diagnosis, type of antidiabetic therapy and its duration).

Statistical analysis of the relationship of clinical parameters and various glucose-lowering means carried by multivariate logistic regression adjusted for age, sex, race, smoking, alcohol consumption, body mass index, family history of prostate cancer, duration of type two diabetes and use insulin. Since many of the patients used a combination antidiabetic therapy, the drugs and their combinations changed over time, and the number of patients with monotherapy was small, the final analysis was performed in subgroups of participants ever or never use insulin, stimulants, its secretion, metformin and thiazolidine.

The study included 973 "case" (including 259 patients with type two diabetes) and 863 "control" (including 109 patients with type two diabetes). The groups were matched by sex and educational level, but among the "controls" were less than those with black skin and the age of 70 years.

In the population study of the factors independently associated with risk of prostate cancer, were smoking (odd's ratio [OR] - 1.45, p <0,001), alcohol consumption (OR- 1.25, p = 0,043), family history of prostate cancer (OR- 1,62 p <0,001), overweight (OR - 2.58, p <0.001) and obesity (OR - 4.21, p <0,001). Type 2 diabetes also increases the risk of prostate cancer in a 2.37-fold (95% confidence interval [CI], 1,84-3,06, p<0,001), including the duration ofthedisease up to 2years, OR was 4.50 (p <0,001)3 to5 years - 1.71 (p = 0.04), more than 5years - 1.52 (p = 0,028). Frequency 0, 028).of insulin,stimulants of insulin secretion (sulfonylureas andmeglitinidov),metformin and other antidiabeticfundsto groups "cases" and"control" was comparable. The entire population of study participants used of stimulants of insulin secretion and increased the risk of thiazolidinediones unreliable prostate cancer (OR - 1.78, p = 0.231 and OR - 1.08, p = 0.0883 respectively). In contrast, treatment with metformin was accompanied by a statistically significant reduction in the risk of prostate cancer (OR - 0.38, 95% CI 0,21-0,67, p = 0, 001). When analyzing only patients with type two diabetes using insulin and its secretion stimulants increased the risk of prostate cancer in 4.99 and 2.52 times, respectively (p <0.001 and p = 0, 005), while treatment with metformin reduced the risk by 62%(OR- 0 ,0,,95%CI 0,22-0,69, p = 0, 001). ThiThiazolidinedione's therapy was accompanied by misleading trend to an increased risk of disease (OR1.55, p = 0.213). In the analysis of the participants had never used the insulin, the relationship stimulators of insulin secretion with an increased risk of prostate cancer and metformin with Tesero protective effect remained statistically significant (OR- 3.82, p = 0.001 andOR - 0.44, p = 0.019 respectively). After exclusion of participants with hypotype,towelettes duration of ≤ 2 years (which makes it unlikely that the inclusion of patients with diabetes caused by prostate cancer), insulin and metformin, respectively, increased and decreased risk of developing prostate cancer (OR- 5.04, p <; 0.001R- 0.41, p = 0.020). On the contrary, the relationship with prostate stimulators of insulin lost its statistical significance (OR - 1.74, p = 0.160), although the number of "cases" and "control" was small (n = 48 and n= 20, respectively). Relatively short (≤ 2 years)using insulin and stimulants to secretion was accompanied by significantly higher risk of prostate cancer(OR - 11.3, p <0.001lt; 0.001 4.94, p =0,001). A0, 001). same time, treatment with metformin reduced this risk(OR - 0.34, p =0,001). I0, 001).ast,during prolonged glucose-lowering therapy (> 5 years) association with prostate cancer risk remained only for metformin (OR - 0.18, p <0,001). After exclusion of patients with type, two diabetes duration of ≤ 2 years of use for more than five years metformin has confirmed its protective effect against prostate cancer (OR - 0.30, p = 0.005). Long-term insulin therapy, in contrast, showed an increased risk of prostate cancer (OR - 2.78, p = 0.049).
In this case-control study first demonstrated a statistically significant association between the type of antidiabetic therapy and risk of prostate cancer. In particular, the use of metformin, especially long-term (over five years) significantly reduced the risk of prostate cancer compared with patients with type two diabetes, never used this drug. In addition, the findings suggest that therapy with insulin or stimulants to secretion is accompanied by an increased risk of prostate cancer the latter observation, owing to the small number of cases to be confirmed in large clinical trials.

The study design is impossible to establish with anything related to lower risk of prostate cancer with metformin - a less severe type 2 diabetes, for treatment, which was chosen as metformin, or with better control of type 2 diabetes with metformin or with its direct antineoplastic effect (the latter found in the experiments). Nevertheless, if kantseroprotektivny effect of the drug is confirmed in further studies, metformin may be a good tool for primary prevention of prostate cancer in patients with type 2 diabetes, conclude authors of the publication.

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