The strongest associations between diabetes and colorectal cancer risk were observed in participants with a recent diabetes diagnosis and those who had not undergone recent colonoscopy, underscoring the significance of cancer screening.
“The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening,” the study authors said.
Type 2 diabetes (T2D) and CRC have historically imposed a greater burden on individuals with low socioeconomic status and those of African American race. Although diabetes is increasingly recognized as a risk factor for CRC, there is still a lack of research on the connections between diabetes and CRC in these specific populations. With the expectation that T2D will be linked with CRC risk already, this study focused on the increased risk for patients in understudied populations.
This cohort study utilized data from the prospective Southern Community Cohort Study conducted in the United States, which recruited participants from 12 states between 2002 and 2009 and conducted 3 follow-up surveys up to 2018. Among approximately 85,000 participants, 86% were recruited from community health centers and 14% were enrolled through mail or telephone from the same 12 recruitment states.
Participants self-reported their physician-diagnosed diabetes and their age at diagnosis through surveys conducted at enrollment and in 3 subsequent follow-ups. Participants were excluded if they had less than 2 years of follow-up, had a prior cancer diagnosis—excluding nonmelanoma skin cancer—at the time of enrollment, had missing information on their diabetes status at enrollment, received their diabetes diagnosis before age 30, or did not have diabetes at enrollment and did not participate in any follow-up surveys. Data analysis was conducted between January and September 2023.
Of the 54,597 included participants, the median (IQR) age at enrollment was 51 (46-58) years; 34,786 (64%) were female; 36,170 (66%) were African American; and 28,792 (53%) reported an annual income below $15,000. In total, 289 of 25,992 participants with diabetes and 197 of 28,605 participants without diabetes developed CRC.
Diabetes was associated with 47% increased risk of CRC (HR, 1.47; 95% CI, 1.21-1.79). This association was more pronounced among participants who had not undergone colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and those with a history of smoking (HR, 1.62; 95% CI, 1.14-2.31), possibly because of differences in cancer screening, the authors noted. Additionally, stronger associations were observed in participants with a recent diabetes diagnosis, with a diabetes duration of less than 5 years compared with 5 to 10 years (HR, 2.55; 95% CI, 1.77-3.67), potentially due to recent screening practices.
The associations between T2D and CRC risk remained consistent regardless of adjustment for body mass index, and were similar when the researchers looked at colon and rectal cancer separately. However, these associations were somewhat stronger in participants who had a diabetes diagnosis at the time of enrollment (HR, 1.59; 95% CI, 1.28-1.97) compared with those who developed T2D during the study (HR, 1.28; 95% CI, 0.99-1.66). Additionally, the associations were more pronounced in female participants (HR, 1.59; 95% CI, 1.24-2.04) compared with male participants (HR, 1.27; 95% CI, 0.93-1.75).
Through most of the study analyses, the researchers excluded participants who did not report a diabetes diagnosis at enrollment and lacked follow-up questionnaire data. However, to assess the impact of this exclusion on the findings, they performed a sensitivity analysis on the entire analytical cohort, which included these participants who were originally excluded. In the sensitivity analysis that included the full participant cohort, the link between diabetes and CRC was weaker and closer to neutral (HR, 1.14; 95% CI, 0.98-1.33).
The study found minimal evidence of diabetes and CRC risk interaction by race and ethnicity (P for interaction = .33), sex (P for interaction = .33), obesity (P for interaction = .83), or income (P for interaction = .93). However, the associations between diabetes and CRC risk differed based on smoking status, as diabetes was linked to a higher risk in former and current smokers, but not in never smokers, which is potentially attributed to increased CRC screening among the latter group (P for interaction = .04).
“Increased interactions with the health care system following a diabetes diagnosis, including increased referrals to CRC screening, may be important for mitigating the harm of diabetes-related metabolic dysfunction, particularly in early diabetes, on CRC risk,” the authors concluded.
Lawler T, Walts ZL, Steinwandel M, et al. Type 2 diabetes and colorectal cancer risk. JAMA Netw Open. Published online November 14, 2023. doi:10.1001/jamanetworkopen.2023.43333