Diabetes and endometrial cancer: effect modification by body weight, physical activity and hypertension

Abstract

Among 777 endometrial cancer cases and 1550 controls from Italy and Switzerland, odds ratio was 1.7 (95% confidence interval: 1.2 -2.5) for diabetes, and 5.1 for obese diabetic women as compared with non-obese non-diabetic ones. Diabetes shows a supramultiplicative effect with body mass index, but not with physical activity or hypertension. An increased risk of endometrial cancer in diabetic women has often been reported (Parazzini et al, 1991(Parazzini et al, , 1999Brinton et al, 1992;La Vecchia et al, 1994;Shoff and Newcomb, 1998;Salazar-Martinez et al, 2000;Weiderpass et al, 2000;Anderson et al, 2001;Sharma et al, 2001;Cook et al, 2006;Friberg et al, 2007). Overweight and obesity are major risk factors for both conditions since they are related to increased endogenous oestrogen levels (Parazzini et al, 1991;Calle et al, 2003;Cook et al, 2006). Although the association between diabetes and endometrial cancer may be partly or largely accounted for by the higher body weight of endometrial cancer cases, it has been found to persist after adjustment for body mass index (BMI) (Brinton et al, 1992;La Vecchia et al, 1994;Parazzini et al, 1999;Salazar-Martinez et al, 2000;Friberg et al, 2007).A few of the above studies have investigated the combined role of diabetes and BMI on risk, finding a higher risk among obese diabetic women, most of these, but not all (Anderson et al, 2001), reporting some excess risk also among non-overweight diabetic women.Diabetes is associated with hypertension and physical inactivity, which in turn have been related to endometrial cancer risk (Parazzini et al, 1999; Cust et al, 2007;Voskuil et al, 2007). In a Swedish cohort study of 225 cases of endometrial cancer, the relative risk was 2.7 for diabetic women reporting low physical activity and 1.1 among those reporting high physical activity (Friberg et al, 2007). In an Italian case -control study, the association with diabetes was of similar magnitude in women with or without hypertension (Parazzini et al, 1999).We therefore investigated whether the association between diabetes and endometrial cancer was modified by BMI, physical activity and hypertension in two case -control studies from Italy and Switzerland. MATERIALS AND METHODSWe analysed the combined data of two case -control studies of endometrial cancer, the first conducted in the greater Milan area and the Swiss Canton of Vaud between 1988 and 1994 on 410 cases and 753 controls (Augustin et al, 2003), the second conducted in the provinces of Pordenone and Milan, in northern Italy, and Naples, in southern Italy, in 1992-2006 on 454 cases and 908 controls. A subset from the latter included in a previous study was excluded . This left a total of 777 women (aged 18-79 years, median 61 years) with histologically confirmed endometrial cancer, with no previous diagnosis of cancer, and 1550 control women (aged 18-80 years, median 61 years) admitted to the same network of hospitals as cases for acute, non-neoplastic, and non-gynaecologic, nonhormone-related, non-metabolic conditions. Wom...

Dietary glycemic index, glycemic load, and the risk of endometrial cancer

“…insulin, IGF, and estrogen) that have been linked to endometrial carcinogenesis (Kaaks et al, 2002). A few studies have shown direct associations of the risk of endometrial cancer with GI, GL, insulin, and IGF and diabetes (Augustin et al, 2003;Silvera et al, 2005;Lucenteforte et al, 2007), although others have reported no association (Folsom et al, 2003;Cust et al, 2007). It has also been hypothesized that high levels of GI and GL may increase the level of markers of inflammation (Mann, 2007), such as C-reactive protein, and a recent nested case-control study reported an increased risk for endometrial cancer in patients with elevated prediagnostic levels of inflammatory markers (Dossus et al, 2010).…”

“…GI and GL were also introduced in the model as continuous variables, and the unit of measurement was the difference between the 80th and the 20th percentile, that is the upper cut point of the fourth and the first quintiles, computed on the distribution of controls. Because diabetes is known to be associated with GL (Barclay et al, 2008) and is also positively associated with the risk of endometrial cancer (Cook et al, 2006;Lucenteforte et al, 2007), we also repeated the analyses excluding 53 diabetic cases and 54 diabetic control patients.…”

Predicting the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding: the Norwich DEFAB risk assessment tool

“…Type-II cancers have a non-endometrioid histology and arise in women who are less likely to have the clinical associations seen in type-I cancers (Bokhman, 1983). Several risk factors such as obesity, tamoxifen use, increasing age, hypertension, diabetes, and unopposed use of exogenous oestrogens are strongly associated with increased risk of type-I endometrial cancer (Persson et al, 1989;Soler et al, 1999;Cohen, 2004;Lachance et al, 2006;Friberg et al, 2007;Lucenteforte et al, 2007;Renehan et al, 2008). Early menarche and late menopause have also been implicated due to prolonged oestrogen stimulation of the endometrium.…”

High rates of endometrial cancer among Pacific women in New Zealand: the role of diabetes, physical inactivity, and obesity

“…A Swedish cohort [29] corroborates this estimate with an RR of 9.61(95 % CI 4.66-19.83) for the same group compared with women with BMI \ 25 kg/m 2 , high physical activity and no diabetes. Only one paper found a statistically significant interaction (on a multiplicative scale) between diabetes mellitus and BMI [49] with most papers reporting nonsignificant interactions [29,[50][51][52][53][54]. A statistically significant interaction between diabetes mellitus and physical activity was reported by one paper [29], and only one other paper reported that there was no suggestion of interaction between diabetes and other risk factors that were examined [43].…”