Sex-Specific Association between Family History of Diabetes and Risk of Colorectal Cancer: Two Prospective Cohort Studies.

Cancer Prev Res (Phila)

Type 2 diabetes (T2D) is associated with increased risk of colorectal cancer. It remains unclear whether family history of diabetes influences colorectal cancer risk and relevant biomarkers. We followed 101,323 women from the Nurses' Health Study (1982-2012) and 48,542 men from the Health Professionals Follow-up Study (1988-2012), free of cancer and inflammatory bowel disease at baseline. Participants reported whether any of their first-degree family members ever had diabetes in multiple questionnaires administered biennially. Plasma levels of colorectal cancer-related biomarkers were measured in subsets of participants from previous nested case-control studies. We documented 1,950 colorectal cancer cases in women and 1,173 colorectal cancer cases in men. After adjustment for potential confounders including obesity and diabetes, the hazard ratio (HR) for colorectal cancer among men who had family history of diabetes was 1.19 [95% confidence interval (CI), 1.04-1.36) as compared with those who did not. The corresponding HR was 1.06 among women (95% CI, 0.96-1.17). Interestingly, for individuals younger than 60 years, these associations appeared stronger among men (HR, 1.65; 95% CI, 1.15-2.38) and possibly among women (HR, 1.23; 95% CI, 0.99-1.54). Moreover, family history of diabetes was related to reduced levels of estradiol, sex hormone binding globulin (SHBG), and adiponectin in men, with a greater reduction of SHBG for those younger than 60 years ( for interaction = 0.03). In conclusion, family history of diabetes was associated with increased colorectal cancer risk in men, which may be partly mediated by altered sex hormones and adiponectin. The possible positive association in younger women needs further confirmation. .

Year of Publication
Cancer Prev Res (Phila)
Date Published
2018 09
PubMed ID
PubMed Central ID
Grant list
P01 CA087969 / CA / NCI NIH HHS / United States
U01 CA167552 / CA / NCI NIH HHS / United States
R01 CA137178 / CA / NCI NIH HHS / United States
K24 DK098311 / DK / NIDDK NIH HHS / United States
UM1 CA186107 / CA / NCI NIH HHS / United States
R03 CA176717 / CA / NCI NIH HHS / United States
R01 CA049449 / CA / NCI NIH HHS / United States
K07 CA188126 / CA / NCI NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States