Previously, a few studies have reported an increase in the long-term risk of cancer development among patients with GN. A study based on Danish registry data showed an increased risk of cancer development up to 5 years after a GN diagnosis, while another study based on Norwegian registry data observed an increased risk even 5–15 years after an MN diagnosis [10, 17]. Christiansen et al. reported a 73% increase in the 5-year cancer incidence among patients with nephrotic syndrome, compared to the general population [18]. However, these studies only included data from Western populations, focused especially on MN or nephrotic syndrome, and used registry data that lacked specific clinical information (e.g., immunosuppressant usage or clinical outcomes after cancer development). Therefore, we conducted this study to determine the incidence of de novo cancer in a Korean population of patients with GN, including all major types of GN, through a thorough review of clinical data. Moreover, we assessed differences in the outcomes of mortality and ESRD development according to de novo cancer development in our patient cohort. To the best of our knowledge, this is the first report on the incidence and types of de novo cancers in an Asian population with GN. As the types of GN and the types and incidence of cancer differ by race and ethnicity, this study provides valuable insights into the incidence and outcomes of cancer in Asian patients with GN.
In this study, we identified a de novo cancer incidence of 5.3% in a cohort of Korean patients with renal biopsy-confirmed GN during a mean follow-up duration of 4.4 years. Overall, patients with GN had a higher risk of cancer development, with higher SIR, relative to the general population, particularly in GNs such as MN, IgAN, lupus nephritis, and FSGS. These findings definitely suggest that de novo cancer risk in GN patients was substantially higher risk during follow-up after GN diagnosis.
From our results, the four most common cancer types were colon cancer, hepatocellular carcinoma, papillary thyroid carcinoma, and gastric cancer, all of which are among the six major cancers affecting the general Korean population [21]. These common cancer types differ from those reported in previous reports from Western countries, wherein the greatest increases were observed for non-Hodgkin’s lymphoma and skin cancer in the GN population relative to the general population [10, 17, 22]. The finding of the present and previous studies emphasize that screening for de novo cancer during the follow-up period after GN diagnosis should include cancers that occur most often in the corresponding general population. We note that we were unable to calculate the SIR according to the specific cancer types because of the small number of cancer cases that were observed. Further studies including larger numbers of cases are needed to determine whether patients with GN are at an increased risk of specific types of de novo cancer relative to the general population, particularly in Asian countries.
We identified a pathologic diagnosis of MN, old age, male sex, and low hemoglobin level as independent risk factors for cancer development in GN patients during the follow-up period. Moreover, in subjects with MN, old age (≥ 60 years) was identified as an independent risk factor for cancer development, consistent with the findings of a previous study [17]. Additionally, when we analyzed the outcomes of GN patients according to the cancer development status, those with cancer had an increased risk of mortality but not of ESRD development, especially in MN. As previously noted, our data support the emphasis of cancer surveillance for these high-risk subgroups of GN patients. The early detection of de novo cancers and timely intervention would likely improve the survival outcomes of patients with GN.
The pathophysiologic mechanisms underlying the association between GN and long-term cancer development are unclear. Possibly, GN promotes cancer development through the immunosuppressive effects of nephrosis or uremia [22]. Moreover, the carcinogenic effects of GN treatment might induce de novo cancer development. However, after adjusting for confounding factors, we did not find a significant effect of the use or dosage of immunosuppressant agents on cancer development. We further note that an underlying undiagnosed tumor may induce GN through mechanisms such as antigen production and might be detected as de novo cancer during follow-up [10]. Moreover, infection with a viral pathogen, such as hepatitis B virus, may be an etiological factor in both GN and cancer [23]. We note that GN patients are monitored and closely followed by nephrologists, which may lead to a higher cancer detection rate than in the general population. Additional studies are required to elucidate the physiologic mechanism underlying the association between GN and de novo cancer.
This study has several limitations due to the nature of a retrospective cohort study. First, although we excluded patients who developed cancer within 1 month after diagnosis, patients with hidden underlying malignancies might still have been included. Second, we were unable to determine the specific mechanism underlying the association between GN and de novo cancer from these data. Third, the relatively small number of patients, particularly those with cancer, might reduce the statistical power of our findings. We were also unable to calculate the SIR according to cancer type. Fourth, there is a lack of information about cancer risk factors such as smoking, alcohol consumption, viral infection, and prognostic biomarkers such as anti-PLA2R antibody in MN [24].