Prospective Study of Self-Reported Diabetes and Risk of Upper Gastrointestinal Cancers

Abstract

Background: Although gastric noncardia adenocarcinoma (GNCA) incidence rates in the United States have decreased, the rates of gastric cardia adenocarcinoma (GCA) and esophageal adenocarcinoma (EADC) have increased. Obesity increases the risks of GCA and EADC, and the associations may be partially mediated by insulin resistance. A few case-control studies have shown an association between diabetes and an increased risk of EADC.Methods: We prospectively examined the association between diabetes and upper gastrointestinal (UGI) cancers in a cohort of 469,448 people in the United States, ages 50 to 71 at baseline. Cox proportional hazards regression was used to estimate the HR and 95% CI for diabetes and UGI cancers, controlling for multiple potential confounders, including body mass index (BMI).Results: We observed no association of self-reported diabetes with risk of EADC, HR (95% CI) ¼ 0.98 (0.73-1.31), esophageal squamous cell carcinoma (ESCC), HR (95% CI) ¼ 1.02 (0.60-1.74), or GNCA, HR (95% CI) ¼ 0.98 (0.70-1.37). However, diabetes was significantly associated with an increased risk of GCA, HR (95% CI) ¼ 1.89 (1.43-2.50). The significant association between diabetes and risk of GCA remained after adjustment for BMI, HR (95% CI) ¼ 1.70 (1.28-2.26) and did not differ by BMI strata (P interaction ¼ 0.83). The significant association was unchanged when restricting to only overweight subjects (BMI 25 to 30), HR (95% CI) ¼ 1.83 (1.18-2.85).Conclusions: We found a significant association between self-reported diabetes and increased risk of GCA. Impact: Our results suggest that the metabolic and hormonal changes related to diabetes may play a role in the etiology of GCA independently from BMI. Cancer Epidemiol Biomarkers Prev; 20(5); 954-61. Ó2011 AACR.

Obesity and related risk factors in gastric cardia adenocarcinoma

“…In general, for gastric cancer, when all subtypes are considered together, there is a large body of evidence suggesting a weak association of DM with gastric cancer (overall OR about 1.1-1.2), which is especially skewed toward females and Southeast Asians [40]. Three case-control studies have addressed specifically the relationship between DM and gastric GCA using case-control designs [41][42][43]. Two were from the USA [42,43] and one was from Australia [41], and all used the standard GCA Siewert type 2/3 definition, with DM being self-reported in each study.…”

“…Three case-control studies have addressed specifically the relationship between DM and gastric GCA using case-control designs [41][42][43]. Two were from the USA [42,43] and one was from Australia [41], and all used the standard GCA Siewert type 2/3 definition, with DM being self-reported in each study. Only one of the studies reported a significant association between DM and GCA, suggesting that the relationship between obesity and GCA is unlikely to be due entirely to the prevalence of DM.…”

Diabetes mellitus and risk of gastric cancer

“…Among these 17 studies, nine were cohorts, using incidence and/or mortality rate ratios as the measure of RR [18][19][20][21]23,45,[47][48][49] and eight were diabetic cohorts, using standardized incidence ratio/standardized mortality ratio as the measure of RR [16,17,22,24,[42][43][44]46]. The former nine cohorts included 7 617 638 participants (range: 18 006-4 501 578), and the latter eight diabetic cohorts included 409 048 participants (range: 5066-125 126) with diabetes.…”

“…With respect to the relationship of diabetes with GC development, inconsistent results have been reported [16][17][18][19][20][21][22][23][24]. The purpose of this study was to summarize all available evidence from observational studies to estimate the risk of GC in patients with diabetes following the meta-analysis of observational studies in epidemiology guidelines [25].…”

Plasma insulin, C‐peptide and blood glucose and the risk of gastric cancer: The Japan Public Health Center‐based prospective study

“…2 However, the association between DM and gastric cancer remains to be clarified. Some prospective studies reported that DM determined by questionnaire or medical records is positively associated with gastric cancer, [3][4][5][6] but others found a null association. [7][8][9][10][11][12] However, DM can be easily misclassified when based on self-report of disease in questionnaire survey or medical records.…”