Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in non-diabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable-adjusted hazard ratios (HR) of cancer incidence and mortality for non-diabetic participants with values ≥5.7% (elevated), non-diabetic participants with <5.0% (low), and diabetic participants all compared with non-diabetic participants with 5.0–5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with non-diabetic women with normal glycated hemoglobin, non-diabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Non-diabetic women with low values also had increased risk. Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in non-diabetic and diabetic men, and diabetes were not statistically significantly associated with total cancer risk. Our findings support the hypothesis that chronic hyperglycemia, even in the non-diabetic range, increases cancer risk in women. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer, especially in women.

Aims  Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI). Methods and results  Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70–0.84); all-cause mortality 0.71 (0.63–0.80); CV mortality 0.68 (0.57–0.81); MI 0.81 (0.73–0.91); ischaemic stroke 0.76 (0.62–0.93); heart failure hospitalization 0.73 (0.63–0.85), and coronary artery revascularization 0.86 (0.79–0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin. Conclusions  Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.

Background To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer. Methods We conducted a nested case-control study of men who had a radical prostatectomy in 1993–2001. 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single nucleotide polymorphisms (SNPs) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR, IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10, was associated with a higher risk of recurrence (OR=1.76, 95% CI: 1.00–3.10), and the minor allele (G) in rs1800896, known to produce more interleukin-10, was associated with a lower risk of recurrence (OR=0.66, 95% CI: 0.48–0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and two common NOS2 haplotypes were associated with recurrence. Conclusion Variation in IL10, CRP, GSTP1, IL1B, and NOS2 was associated with recurrence independent of pathologic prognostic factors. Impact This study supports that genetic variation in immune response and oxidation influence recurrence risk and suggests genetic variation in these pathways may inform prognosis.