SHORT REPORT Dietary carbohydrate, fibre, glycaemic index, glycaemic load and the risk of postmenopausal breast cancer Graham G. Giles 1,2,3 * , Julie A. Simpson 1 , Dallas R. English 1,2,3 , Allison M. Hodge 1 , Dorota M. Gertig 2 , Robert J. MacInnis 1 and John L. Hopper 2 1 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia 2 Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia 3 Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia Evidence that the insulin pathway may be involved in breast carci- nogenesis has increased the interest in dietary factors that influ- ence insulin secretion and resistance. We investigated dietary car- bohydrate, fibre, glycaemic index (GI) and glycaemic load (GL) in a prospective study of 324 breast cancers diagnosed in 12,273 post-menopausal women. Although an increase of 1 standard devi- ation in carbohydrate was marginally associated with risk of breast cancer, relative risk (RR) 1.31 (95% CI, 0.98, 1.75), there were no significant associations with fibre, 1.08 (0.92, 1.26), GI, 0.98 (0.88, 1.10) or GL, 1.19 (0.93, 1.52) or with carbohydrate foods (bread, rice, pasta). The RR for carbohydrate and localized disease was elevated, 1.40 (1.02, 1.92), but like those for fibre, GI and GL did not differ significantly between localized and non- localized disease. RRs for grade I, but not grade II or III, tumours were elevated for fibre, 1.38 (1.08, 1.75), carbohydrate, 1.56 (1.08, 2.25) and GL, 1.41 (1.01, 1.98) but not for GI, 0.84 (0.65, 1.09). The RRs for fibre and oestrogen receptor (ER) positive (1) and progesterone receptor (PR) positive (1) tumours, 1.36 (1.10, 1.67), differed significantly from those for ER positive (1) and PR nega- tive (2) tumours, 1.01 (0.61, 1.69) and ER2/PR2 tumours, 0.65 (0.43, 0.99), p 5 0.005. Our data do not support a strong role for GI and GL in breast carcinogenesis but suggest that increased intake of fibre and carbohydrate may be associated with the diag- nosis of cancers of more favourable prognosis. ' 2005 Wiley-Liss, Inc. Key words: breast cancer; dietary fibre; carbohydrate; glycaemic index; glycaemic load; post-menopausal women; cohort study; Australia There is mounting evidence that diets characterised by energy imbalance and low physical activity may be important to the risk of many chronic diseases, including breast cancer, and this risk might be mediated by insulin and insulinlike growth factors (IGFs). 1–3 The amount and type of dietary carbohydrate expressed as glycaemic index (GI), or glycaemic load (GL), contribute to variation in blood glucose levels and the body’s insulin response. 4 Chronic hyperinsulinaemia consequent upon particular dietary GI and GL may lead to increased levels of circulating IGFs that may increase the cancer risk by encouraging cellular proliferation or by other as yet unknown mechanisms. 5 Although positive associations between the risk of post-meno- pausal breast cancer and intakes of GI and GL have been reported by retrospective and case-control studies, 6–9 5 prospective studies have provided little supportive evidence with respect to intakes in adult life. 10–14 We investigated associations between dietary car- bohydrates, GI and GL, and dietary fibre, and risk of invasive breast cancer in a prospective study of post-menopausal women with a wide range of relevant dietary exposures and detailed tumour characteristics. Material and methods Study cohort and subjects In 1990–94, the Melbourne Collaborative Cohort Study (MCCS) recruited 41,528 people (24,479 women) from the Mel- bourne metropolitan area. Most participants (99.3%) were aged 40–69 years. Migrants from Italy and Greece were deliberately recruited to increase the range of dietary exposures available. 15 It was approved by The Cancer Council Victoria’s Human Research Ethics Committee. Subjects were excluded from analysis if they had a confirmed invasive breast cancer prior to baseline (386 women) and were pre-menopausal or of unknown menopausal status at baseline (10,374). A further 1,446 post-menopausal women were excluded because they had a self-reported heart attack, diabetes and angina at baseline; had missing data for the food frequency questionnaire (FFQ); or extreme values of total energy intake (<1st percentile and >99th percentile). The analysis was based on a total of 12,273 post-menopausal women. Dietary assessment Dietary information was collected at baseline using a 121 item, self-administered FFQ, specifically developed for the MCCS. 16 Glycaemic index (GI) is a method of ranking foods on the basis of the blood glucose response to a given amount of car- bohydrate from that food. GI values of individual food items, rel- ative to glucose, were obtained from the 2002 International table of GI and glycaemic load (GL) values. 17 Where there was more than one value, GI values were averaged, with preference being given to Australian figures. Dietary GL was computed by sum- ming the product of carbohydrate intake from each food with the GI for that food. GL was divided by total carbohydrate intake to obtain dietary GI, that is, an average of individual food GI val- ues, weighted according to their contribution to carbohydrate intake. Further detail on the GI calculations has been published elsewhere. 18 Alcoholic beverages were not included in the over- all GI. Intakes of energy, fibre (total and separately from cereals, fruits, vegetables, legumes and potatoes), total carbohydrate, total starch and total sugars were computed using Australian food composition tables. 19 The food groups investigated were total cereal products, breakfast cereal, bread, wholemeal bread, white bread, rice, and pasta and noodles as number of times eaten per week. Other measures At interview, questions were asked about reproductive history, country of birth, alcohol intake, physical activity, highest level of education and use of hormone replacement therapy (HRT) and oral contraceptives (OC). Ascertainment of invasive breast cancer cases All women consented to us accessing their medical records, and their cancers were ascertained by the Victorian Cancer Registry, which has complete coverage of the cohort. Altogether, 324 inva- *Correspondence to: Cancer Epidemiology Centre, The Cancer Coun- cil Victoria, 1 Rathdowne Street, Carlton South, VIC 3053, Australia. Fax: 161-3-9635-5330. E-mail: Graham.Giles@cancervic.org.au Received 1 May 2005; Accepted after revision 17 August 2005 DOI 10.1002/ijc.21548 Published online 10 October 2005 in Wiley InterScience (www.interscience. wiley.com). Int. J. Cancer: 118, 1843–1847 (2006) ' 2005 Wiley-Liss, Inc. Publication of the International Union Against Cancer