We thank Rigalleau et al. (1) for their interest in our article regarding chronic kidney disease measures and cancer risk (2) and their valuable comments. As they pointed out, we did not conduct a subgroup analysis by diabetes status. We focused on demographic subgroups (i.e., age and sex) in our study, because these are key elements for cancer screening.
Nonetheless, in answer to the comment by Rigalleau et al., we newly performed an analysis stratified by diabetes status. We observed largely similar results as the main analysis. Specifically, urine albumin-to-creatinine ratio (ACR) was not significantly associated with overall cancer incidence but was significantly associated with overall non–prostate-cancer incidence regardless of diabetes status at baseline (Figure 1). The association with overall non–prostate-cancer incidence in the range of ACR >300 mg/g appeared more evident among those with diabetes than among those without diabetes, but importantly, the interaction was not statistically significant (P for interaction = 0.268). Also, we should keep in mind that in our community-based cohort there were a limited number of participants without diabetes at this level of ACR.
Figure 1.
Adjusted hazard ratios and 95% confidence intervals for overall cancer and overall non–prostate-cancer incidence. Linear splines of albumin-to-creatinine ratio (ACR) with 3 knots (10, 30, and 300 mg/g), with the referent at 5 mg/g. A) Overall cancer incidence in those without diabetes. B) Overall cancer incidence in those with diabetes. C) Overall non–prostate-cancer incidence in those without diabetes. D) Overall non–prostate-cancer incidence in those with diabetes. Model adjusted for age, sex, race-center, body mass index, total cholesterol, high-sensitivity C-reactive protein, history of cardiovascular disease, family history of cancer, smoking status, alcohol amount, statin use, aspirin use, hypertension, and estimated glomerular filtration rate. P for interaction for overall cancer incidence = 0.374. P for interaction for non–prostate-cancer incidence = 0.268.
Our finding regarding the lack of association of albuminuria with overall cancer risk in diabetes is consistent with the previous report from ADVANCE (3). In contrast, a small study (n = 646) found an elevated risk of cancer mortality in diabetes patients with proteinuria (4). Given that our study demonstrated a stronger association when prostate cancer was excluded, the discrepancy across these studies might be due to the composition of site-specific cancer.
In conclusion, we did not observe evident difference in the albuminuria-cancer relationship between persons with and without diabetes. Nonetheless, additional studies are warranted to investigate the association between albuminuria and cancer specifically in patients with diabetes.
ACKNOWLEDGMENTS
The Atherosclerosis Risk in Communities study has been funded in whole or in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contracts HHSN268201700001I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I, and HHSN2682017000021). Studies on cancer in the Atherosclerosis Risk in Communities study are also supported by the National Cancer Institute (grant U01 CA164975). This work was additionally supported by P30 CA006973 from the National Cancer Institute. Cancer incidence data have been provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W. Preston Street, Room 400, Baltimore, Maryland 21201. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries (Centers for Disease Control and Prevention) for the funds that helped support the availability of the cancer registry data.
The authors thank the staff and participants of the ARIC study for their important contributions.
The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest: none declared.
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