Date Published: November 11, 2015
Publisher: Public Library of Science
Author(s): Chin-Hsiao Tseng, Demetrios Vavvas.
To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus.
A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively. The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end-stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization. Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.
Patients with type 2 diabetes mellitus suffer from a significantly higher risk of cancer involving the breast, endometrium, stomach, colorectum, liver, pancreas, urinary bladder, and lymphoid tissue [1–11]. The mechanisms of such an increased cancer risk in the diabetic patients may be related to insulin resistance, hyperinsulinemia, proinflammatory status and increased oxidative stress [1,12]. Although most studies conducted in western countries suggest a lower risk of prostate cancer in patients with type 2 diabetes mellitus , studies conducted in Taiwan and China do not conclude similarly and on the contrary support a higher risk of prostate cancer in patients with type 2 diabetes mellitus in terms of incidence [14,15], prevalence  and mortality . Therefore, ethnical differences may exist when the risk of specific cancer types are compared between patients with diabetes mellitus and individuals without diabetes mellitus.
This study was approved by an ethics review board of the National Health Research Institutes with an approval number 99274. The National Health Research Institutes is the only organization approved, as per local regulations, for handling the NHI reimbursement database for academic research. For the protection of privacy, the identification information of individuals was scrambled and the patient records/information was anonymized and de-identified prior to analysis. Written informed consent from the participants to use their clinical records in the study was not obtained, because this is not required according to local regulations. The analyses and reporting of the study were conducted according to the STROBE guidelines [30,31], by using the checklist for observational studies (version 4) .
The baseline characteristics between the diabetic patients and the non-diabetic people are compared in Table 1. All of the variables differed significantly between the two groups. The diabetic patients were characterized by older age, female predominance, having more comorbidities, higher prevalent rates of taking medications, more living in Southern and Kao-Ping and Eastern regions, and less involvement in occupation class I (i.e., civil servants, teachers, employees of governmental or private business, professionals and technicians). The mean diabetes duration in the diabetic patients was 5.8 years.
This is the first study showing a definitely higher risk of kidney cancer in patients with known type 2 diabetes mellitus in the Chinese population in Taiwan (Tables 2 and 3). Furthermore, there seems to be a dose-response relationship between diabetes duration and kidney cancer risk when both diabetic patients and non-diabetic people were analyzed together (Table 3), though this could not be similarly demonstrated when only diabetic patients were analyzed (Table 4). Kidney cancer is associated with a poor prognosis and nearly half of the patients die within 5 years after diagnosis . In the present study, diabetes mellitus was unlikely caused by kidney cancer, because the association was consistently observed when patients with a diagnosis of diabetes mellitus <5 years were excluded in the analyses (Table 2), taking into account that diabetes mellitus diagnosed more than 5 years before kidney cancer can hardly be a consequence of the carcinogenic process. Source: http://doi.org/10.1371/journal.pone.0142480