original article

Annals of Oncology 22: 1332–1338, 2011 doi:10.1093/annonc/mdq595 Published online 3 December 2010

Carbohydrate intake, glycemic load, glycemic index, and risk of ovarian cancer
C. M. Nagle1*, F. Kolahdooz2, T. I. Ibiebele1, C. M. Olsen3, P. H. Lahmann3, A. C. Green4 & P. M. Webb1; Australian Cancer Study (Ovarian Cancer) and the Australian Ovarian Cancer Study Group
1 Gynaecological Cancer Group, Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Australia; 2Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; 3Cancer Control Group; 4Cancer and Population Studies Group, Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Australia

Downloaded from annonc.oxfordjournals.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25, 2011

Received 20 June 2010; revised 24 August 2010; accepted 31 August 2010

Background: Our objective was to determine the relationship between dietary glycemic load (GL), glycemic index
(GI), carbohydrate intake, and ovarian cancer risk in a population-based case–control study.

Patients and methods: A self-administered questionnaire was used to collect data on demographic and lifestyle
factors, and a food frequency questionnaire was used to collect dietary information from 1366 women with ovarian cancer and 1414 population controls. Results: GL was positively associated with ovarian cancer. The adjusted odds ratio (OR) for the highest versus the lowest quartile of intake was 1.24 [95% confidence interval (CI) 1.00–1.55, P for trend = 0.03]. Fiber intake was inversely associated with risk. The OR comparing women in the highest fiber-intake group with those in the lowest was 0.78 (95% CI 0.62–0.98, P for trend = 0.11). We found no association between GI, carbohydrate intake, and ovarian cancer. In analyses stratified by body mass index, the risk estimates for GL, carbohydrate, and sugar were higher among overweight/obese women; however, the interaction term was only significant for sugar (P for interaction = 0.004). Conclusions: Our results suggest that diets with a high GL may increase the risk of ovarian cancer, particularly among overweight/obese women, and a high intake of fiber may provide modest protection. Key words: glycemic index, glycemic load, ovarian cancer

original article

Few of the established risk factors for ovarian cancer are readily modifiable. Multiparity, oral contraceptive (OC) use, breastfeeding, previous tubal sterilization, or hysterectomy are all established protective factors, while advancing age and family history are associated with increased risk of ovarian cancer [1]. The search for ways to reduce risk has led to interest in investigating dietary correlates of disease. Longterm consumption of a diet high in carbohydrates can lead to chronic hyperinsulinemia and it has been hypothesized that hyperinsulinemia may increase risk of ovarian cancer by lowering insulin-like growth factor binding protein (IGFBP) concentrations, thereby increasing the bioavailability of insulin-like growth factor 1 (IGF-1) [2, 3]. Increased IGF-1 reduces apoptosis, stimulates cellular proliferation and sex steroid synthesis, and decreases the concentration of sex hormone–binding globulin (SHBG), all
*Correspondence to: Dr C. M. Nagle, Genetics and Population Health Division, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queenlands 4029 Australia. Tel: +61-7-3362-0265; Fax: +61-7-3845-3502; E-mail: Christina.Nagle@qimr.edu.au

of which have been implicated in the development of ovarian cancer [2, 3]. Previous epidemiological studies of dietary carbohydrates in relation to ovarian cancer risk have yielded inconsistent results [4–9]. However, because postprandial insulin response varies by the type, amount, and rate of digestion of carbohydrates, it has been hypothesized that the quantity and quality of carbohydrate consumed might be important in ovarian carcinogenesis [10–13]. On this basis, three previous studies have examined the association between glycemic load (GL), glycemic index (GI), and ovarian cancer risk and two of these studies have observed increased risks, particularly among postmenopausal women [13–15]. Fiber may also play a role in ovarian carcinogenesis by lowering circulating concentrations of estrogens and increasing concentrations of IGFBP-3, the primary binding protein for IGF-1 [16, 17]. The results of previous epidemiological studies are mixed, with two prospective studies showing no evidence of an association [5, 18]. We tested the hypothesis that high GL and GI are associated with increased ovarian cancer risk and secondly, that dietary carbohydrate and fiber intake are also implicated in the

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6 versus 56. postmenopausal.04). 2011 results Cases were slightly older than controls (mean 57.3 years) and were less likely to have continued their education beyond high school (Table 1). frequency matched to the case series by age (in 5-year groups) and state of residence.00–1. 26 cases and 3 controls with more than 10% of FFQ items missing. We conducted subgroup analyses to examine whether the associations between dietary carbohydrates. and all participating hospitals.008). The study was approved by the human research ethics committees at the Peter McCallum Cancer Centre. and were also more likely to have had a hysterectomy.11).9 (overweight). The statistical significance of any observed stratum differences was assessed by including a cross-product term in regression models. 1612 (94%) returned the main study questionnaire. 1615 (47%) consented to participate. Further adjustment for dietary fiber intake strengthened the association. OC use (never. the cancer councils of New South Wales.62–0. For the present analyses. GI. As the magnitude of the insulin response to carbohydrate intake is substantially greater in the presence of insulin resistance [19]. Volume 22 | No. (2008) [24]. if their diet had changed in the last 6–12 months.05 were considered statistically significant. 1–2. All tests were two-sided. have a family history of breast or ovarian cancer. and P values <0. and dietary carbohydrates might be stronger among overweight and obese women. Tests for trend were carried out over categories of intake.28. This suggests that the observed association between fiber and ovarian cancer risk was at least partly due to fruit and vegetable intake. Women aged 18–79 years diagnosed with epithelial ovarian cancer during this period were ascertained through treatment clinics and state cancer registries. 590 women recruited before surgery were excluded because their final diagnosis was not primary epithelial ovarian cancer. Other potential confounders that were not included in the final models since they did not alter risk estimates by >10% were family history of breast or ovarian cancer in a first-degree relative.32 (95% CI 1. and ‡60 months). 95% CI 0. those in the highest quartile had a 24% increased risk of ovarian cancer (95% CI 1. however. Women provided detailed health and lifestyle information via a selfadministered questionnaire [20]. Of the 3442 eligible women contacted. but modified for use in Australia [22. With additional adjustment for GL. ‡30 (obese)] [26]. 19 because their cancer was first diagnosed before the start of the study period.Annals of Oncology original article college.03). smoking. University of Melbourne. Data not available in FoodWorks were supplemented with GI values obtained from tables compiled by Atkinson et al.78 (95% CI 0. Downloaded from annonc. log transformed energy intake (kilocalorie). the risk estimates across quartiles of fiber intake were essentially unchanged. After surgery. 25]. We also found that higher intake of fiber was inversely associated with risk of ovarian cancer. and clear cell). leaving a final group of 1366 cases and 1414 controls for analysis. leaving 1509 control women. The overall GI was calculated by dividing the total dietary GL by the total available carbohydrate intake. to have had a tubal ligation. hysterectomy. Briefly. we excluded 157 cases and 48 controls who did not return the FFQ. 2745 women with suspected ovarian cancer were invited to participate and. Cases were less likely than controls to have ever used OCs. talc use. however. and body mass index (BMI) (in kilogram per meter square). To calculate GL and GI. adjusted for potential confounders including age (years). tubal ligation. Dietary information was obtained using a 136-item semiquantitative food frequency questionnaire (FFQ) based on the instrument developed by Willett et al.. use talc in the perineal region. 6 women with a history of ovarian cancer. [21]. Cases were asked to report their usual frequency of consumption in the year before their diagnosis or. 1. <60 months. We repeated these analysis excluding women who reported a history of diabetes (n = 165) or polycystic ovary syndrome (n = 48) and found the same associations. 1. Compared with women in the lowest quartile. and university). We calculated total dietary GL of a food item by multiplying the amount of carbohydrate contained in a specified serving size of the food by the quantity of that food item consumed per day and its corresponding GI value (using glucose as the reference food).19).98). GL. and Victoria. 2319 (84%) agreed to take part. of these. 25–29. or HRT use (never and ever. All analyses were conducted using the SAS statistical package (SAS Institute Inc. We randomly selected potential control women from the Australian Electoral Roll between 2002 and 2005 (enrollment to vote is compulsory in Australia). BMI was classified according to World Health Organization definitions [BMI £ 25 (normal weight). and to drink alcohol (all P < 0.oxfordjournals. 2007) that compiled GI values based on carbohydrate-containing food items to reflect their blood glucose response. 23]. 6 | June 2011 doi:10. Unconditional multivariate logistic regression models were used to estimate the relative risk of ovarian cancer associated with each dietary constituent. and 1. Cases were more likely to be nulliparous. NC). Full details of the study recruitment and data collection have been reported previously [20]. and 1 because she was not an Australian resident at the time of her diagnosis. 99 who reported a previous bilateral oophorectomy. and GI were modified by BMI (<25 and ‡25). and ‡3). Cary.55) and there was a statistically significant dose–response (P for trend = 0. mucinous. level of postschool education (none.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25. GL was positively associated with risk of ovarian cancer (Table 2). we used an Australian GI database (FoodWorks: Professional Edition. and the chi-square test was used for categorical variables. the OR for women in the highest quartile was 0. development of ovarian cancer. endometrioid. modeling the median values of each category as a single continuous variable. South Australia. The analyses were also carried out separately by ovarian cancer subtype (serous. menopausal status (premenopausal and postmenopausal). use of hormone replacement therapy (HRT). we also hypothesized that positive associations between GL. the Cancer Foundation of Western Australia. Of the final 1709 cases. their usual diet. population-based case–control study conducted between January 2002 and June 2005. and 1 who did not complete the main study questionnaire were excluded. patients and methods The Australian Ovarian Cancer Study (AOCS) was an Australia-wide. menopausal status (premenopausal and postmenopausal). Analysis of variance was used to test for differences in means for continuous variables.00. We then summed the values for all carbohydratecontaining foods reported on the FFQ to estimate total GL [24. Further adjustment for fruit and vegetable intake attenuated the OR for the highest versus the lowest fiberintake group (OR 0.87. and alcohol consumption.65. Controls were asked to report how often they consumed a specified amount of each food item in the previous year. the dose–response became statistically significant (P for trend = 0. and 63 cases and 44 controls whose estimated calorie intake was extreme (<700 or >4000 kcal).1093/annonc/mdq595 | 1333 . there was no significant dose–response (P for trend = 0. among postmenopausal women).12. Results are presented as odds ratios (ORs) and 95% confidence intervals (CIs) compared with the lowest intake category.64–1. the ORs across quartiles of GL were 1. parity (0. P for trend = 0. Queensland Institute of Medical Research.05). report being a current smoker.05–1.

1 184 (13. a recent USA prospective study of dietary patterns with 475 cases found an inverse association with increasing quintiles of GL (OR for the highest versus the lowest quintile 0.7) Past smoker 370 (27.9 0.0001 associations between GI.84.3) <0. in a Canadian prospective study with 16.72.003 0. total sugar.13–2.3 6 12.1.6 0. When we stratified by BMI (<25 and ‡25 kg/m2).0) 640 (45.05 Annals of Oncology Age (mean 6 standard 57. Chi-square statistics were used to compare proportions.1) 2078 230 49. and analysis of variance was used to compare means. P for trend = 0. 0.2) Ever use of talc in the 675 (49. <0. we found modest independent associations between GL. Similar associations were also observed for GL and total carbohydrates among overweight/obese women but the tests for interaction did not reach statistical significance. Our results also suggested that the associations with GL.2 Glycemic load 116. GL.002 0.004) [14]. and starch. P for trend = 0.6 6 11. given our results.original article Table 1. P for trend = 0.oxfordjournals.9 All statistical tests were two-sided. 1. fiber intake.7) <60 months 364 (26.7 Fat (g) 70. or starch. No significant associations with ovarian cancer were observed for high intakes of GI. Our findings for GL and ovarian cancer are in agreement with the findings from two of three previous observational studies [13–15]. Our findings for GI are similar to the previous cohort studies [14. and lifestyle characteristics of 1366 cases and 1414 controls included in this study Characteristics Cases.6 128 95 32. and starch. like us.0) 642 (46. 95% CI 0.004) (Table 3).8) ‡10 304 (22.6) Smoking status Never 775 (56.16. or starch. In contrast.1–9.2) Hysterectomy 319 (23.5) 160 (11. Further adjustment for dietary fiber made no material difference in risk estimates for GI.2) Alcohol intake (g/day) 0 313 (22. we found no clear association in our case–control analyses.01) [13].4 0.2 0.3) 297 347 766 386 275 936 478 625 (21. Women in the highest quartile of GL had a 24% excess risk compared with women in the lowest quartile.029) [15].5) perineal region 255 (18.1) (24.0001 discussion In this large-study population of Australian women.6 0.4) 25–29. For GI.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25.6) (54.7 a 166 (11. mucinous. Long-term consumption of a diet high in carbohydrate can lead to chronic hyperinsulinemia that Downloaded from annonc. sugar.9) Pa 0.3 0. they were unable to adjust for menopausal status which the authors state could explain this finding although.3) 238 (16. There were no significant associations or dose–response trends for higher intakes of GI.3) 837 (59.99.9 deviation) College/university 644 (47.7) Family historyc Body mass index (kg/m2) <25 560 (42. Although both these studies reported stronger associations among postmenopausal women.62. and clear cell). we found that the relationship between sugar intake and risk of ovarian cancer was stronger among overweight/obese women (BMI ‡ 25) compared with leaner women (BMI < 25) (P for interaction = 0. and the different ovarian cancer subtypes (serous.4) Postmenopausal 978 (71.6) 1–2 557 (40.0009 0. dietary. however.2) 416 (29.1 0.01 0.09 0. c Family history of breast or ovarian cancer in a first-degree relative.62.0001 0. Volume 22 | No. and sugar were stronger among overweight women.8) 793 (56.5) (66.7) 608 (43. N 56. sugar. adjusted risk estimates modestly increased across quartiles 1.4 Sugar (g) 131 Starch (g) 97 Dietary fiber (g) 31.006 <0. total carbohydrates. 15] but are in contrast to the hospital-based case–control study that found a positive association between GI and ovarian cancer risk [13]. total carbohydrates. sugar. total dietary carbohydrates.0) ‡30 312 (23.02–1. P for trend < 0.3) (27. The finding of an association with GL but not GI suggests that the proportion of high-GI foods in the diet may not be as good as an indicator of physiological response to carbohydrates as GL. 6 | June 2011 .3) Dietary factorsd (median daily intake) Energy (kcal) 2088 Available carbohydrate (g) 232 Glycemic index 50. however.1) Current smoker 221 (16.9) 0.1) (44. There was no significant effect modification by menopausal status or HRT use (results not shown). which also takes into account the quantity of intake of rapidly absorbed carbohydrates [27].1) education Parity 0 267 (19.02).0) 429 (30.01 0. 2011 0. Likewise. 95% CI 1. and 1.9 95.3) (19. for total carbohydrates.4 mean years of followup and 264 incident cases.48.3 0.00.7) 325 (23.2) (51. this seems unlikely.5 719 (50.28 (95% CI 1.1 Protein (g) 94. the risk of ovarian cancer was nearly twofold higher when comparing the highest quartile of GL with the lowest (OR 1. neither found statistical significant effect modification by menopausal status.28–0.9) 3+ 539 (39. The main mechanism by which carbohydrate-rich foods and their GL or GI could influence ovarian cancer risk relates to modulation of the IGF axis. In a large (n = 1031) Italian case–control study. and risk of ovarian cancer. There were no notable 1334 | Nagle et al. GL was associated with an increased risk of ovarian cancer (HR 1.3–2. N Controls.9 450 (34. dietary carbohydrates.1) 383 (27.6) Oral contraceptive use Never 431 (31.6) Ever use of HRTb 458 (47.2 71. total carbohydrates.9 749 (54. endometrioid. while women with the highest fiber intake (38–77 g/day) had a 22% reduced risk compared with women with the lowest fiber intake (10–27 g/day).7 0. b Hormone replacement therapy (HRT) use restricted to postmenopausal women. Comparison of nondietary.7.8) 60+ months 563 (41.5) Tubal ligation 316 (23.9 112. 95% CI 1.0001 0. d Median daily intakes are unadjusted for energy.

0 1.92–1.10 (0. low-GL/GL foods.00–1.14) 0.85–1.0 92 (21–102) 318/377 1.11) 0.01) 0. 18]. menopausal status (premenopausal and postmenopausal). starch. 2011 Table 2. however.91–1. parity (0. and grainy breads.82 (0. college. and sugar among overweight/obese women were consistent with this hypothesis.42) 126 (114–249) 337/358 1. In addition.71–1.52) 1.0 1.03 (0.62–0.35) 1. oral contraceptive use (never.99–1. Multivariate ORs and 95% CI adjusted for age.15 (0.75–1.0 1.24 (1.83–1.11 Downloaded from annonc.85–1.88–1.90 (0.78 (0.83–1.44) 123 (116–131) 353/342 1.08 0. and energy intake (log transformed).92 (0.74–1.88 (0.88) 0.06 (0.9.1093/annonc/mdq595 | 1335 .25) 43 (38–77) 336/359 0.17 0. The modest positive associations we observed between GL.58–0. and ‡30 kg/m2). and ‡60 months).0 23 (10–27) 369/326 1.15 (0. b down regulates IGFBP and thus increases free IGF-1 [2.98 (0.0 197 (94–213) 333/362 1.91) Q3 52 (50–53) 351/344 1.0 1.11 – – 0.51) 245 (235–256) 348/347 1.98) – – 0.33 – – 0.07–1.20 (0.16 (0.03 (0.62–0. this has not been clearly demonstrated [3. such as fruits.16) 91 (82–98) 350/345 1. by increasing SHBG leading to lower circulating levels of unbound estrogen [16.00 (0. 10].93 (0. 6 | June 2011 doi:10.89–1. Like our results. GI.83 (0. 35].03 – – 0.87–1.11 (0. 29].90 (0. Biologic evidence from in vitro studies has shown that IGF-1 directly promotes cellular proliferation and reduces apoptosis. 1–2.25 – – 0.30) 1. Insulin and IGF-1 are also powerful negative regulators of SHBG synthesis in vitro and thus may stimulate ovarian cancer risk through a hormonal pathway.91 – – 0.40) 1.94–1.71 (0. body mass index (<25. have not shown a reduced risk [5. arguably the strongest study design. however. improve insulin sensitivity through their maintenance of relatively low plasma fatty acid levels [33].48) 1. and it can also affect downstream signaling pathways involved in cell growth and proliferation [28.79–1.89–1. and furthermore. 25–29. population-based design.04 0.0 96 (39–111) 343/352 1.73–1.66–1.72–1. most previous case–control studies have supported a beneficial role of fiber [36–40]. they were small (n = 264 and n = 139 cases) and thus possibly suffered from a lack of power to detect modest effects.0 1.13 (0.10 (0.79–1.63) 1.81–1. specifically estrone and estradiol.29) 30 (27–32) 318/377 0.73–1.Annals of Oncology original article Quartile of intake Q1 P for trend Q2 48 (47–50) 330/365 0.21 (0.20 0. vegetables. and high-case response rate.85–1. total carbohydrates.32 (1.96) 0.14 (0.36) 141 (131–235) 362/333 1.23 (0. and fiber intake (daily) and risk of ovarian cancer GI Median (range) Number of cases/controls Age-adjusted ORa Multivariate ORb GL Median (range) Number of cases/controls Age-adjusted ORa Multivariate ORb Total carbohydrates (g) Median (range) Number of cases/controls Age-adjusted ORa Multivariate ORb Total sugar (g) Median (range) Number of cases/controls Age-adjusted ORa Multivariate ORb Total starch (g) Median (range) Number of cases/controls Age-adjusted ORa Multivariate ORb Total fiber (g) Median (range) Number of cases/controls Age-adjusted ORa Multivariate ORb a 45 (24–47) 335/360 1.0 ORs and 95% CI adjusted for age.oxfordjournals.22) 110 (102–116) 333/362 1.92–1. and dietary carbohydrates might be stronger among heavier women because obesity is an important determinant of insulin resistance that exaggerates the adverse metabolic responses to altered carbohydrate intake. and university).36) 1. Two prospective studies.04) Q4 55 (53–71) 350/345 1.28) 1.32) 225 (213–235) 321/374 0.92 (0.0 72 (27–82) 335/360 1.44) 172 (155–302) 371/324 1.06 (0.97–1. and insulin has also been implicated in the etiology of other hormonally driven cancers such as breast [31] and prostate [32]. and ‡3).36) 1. An interaction between IGF-1. total carbohydrates.55) 272 (256–360) 364/331 1. sex hormones. 34. we had detailed information on many potential confounders and the FFQ we used has been shown to Volume 22 | No.97–1. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with glycemic load (GL).09 (0. 3.32) 143 (132–155) 327/368 0. fruit and vegetable dietary patterns and vitamins and fiber patterns [41] have been inversely associated with ovarian cancer in some studies.38) 1.22) 0.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25.73 (0.92–1. level of postschool education (none.09 (0. glycemic index (GI).06 (0. We had hypothesized a priori that the associations between GL.66–1.06 (0.78 (0.58–0.43) 1. <60 months.90–1.11) 0.98 (0.10) 105 (98–114) 344/351 1. Major strengths of our case–control study include its large sample size. 30].006 0. sugar.14) 122 (111–132) 325/370 0. Evidence suggests that slowly absorbed. There is also evidence that dietary fiber may reduce endogenous sex hormone levels.0 1.85 0.33) 35 (32–38) 343/352 0.85–1.

75 (0.43–0. DAMD17-01-1-0729). and smoking history that might differ between those women willing to participate compared with nonparticipants.19) 1.44) 1.52–1.23) 1.65–1. This might be of particular importance because carbohydrate intake.44) 1.44) 1. starch. the Australian Cancer Study was supported by the National Health and Medical Research Council of Australia (grant no.50–0. GI. be a valid measure of diet when compared with weighted food measures [42].94 (0. It has also been suggested that GL/GI may not always adequately reflect the glycemic or insulinemic response to food in mixed meals.77 (0.0 1.30 Downloaded from annonc. we have shown in the largest study to date that diets with a high GL may modestly increase risk of ovarian cancer. these analyses were supported by the Cancer Council Queensland (grant no. starch.85 (0.55–1. funding The AOCS was supported by the U.52.oxfordjournals.55–1.0 1. We have not validated the assessment of GI or GL using another dietary method or against an objective standard.51 1.10) 0.69–1.0 0.50 for total carbohydrates.0 0.41) 1. and ever versus never smoking among our controls were almost identical to those from the NHS. and sugar.71–1. level of postschool education (none. the Cancer Council Tasmania and Cancer Foundation of Western Australia.84 (0.20–2.78–1.49) 0. Our study also has several limitations.35 (1.56) 0.12) 0.0 1. 0.00–1.65 (0.63–1.88 (0. menopausal status (premenopausal and postmenopausal). BMI.73 0.64) 0. fiber.13–2.78 (0.80–1.004 1. 199600).0 0.94 (0. BMI.0 1.89 (0. Assessment of our FFQ relative to an average of 12 days of weighed food records showed moderate correlation coefficients of 0.0 1.0 0.23 (0.01) 0.95 (0. whereas high intake of fiber may decrease risk and that these effects appear to be independent of each other.47. suggesting that bias among our control group is an unlikely explanation of our results [47].09) 0. Distributions of education level.67–1.87 (0.25) 1.34 0.02) 1.80–1.99) 1.73 – 0.76) 1.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25. 496680).16 (0.36 1.24 (0.01) 0. 6 | June 2011 .93–1.40) 0. for women [42].0 0. and ‡60 months).93 (0.79) 0.003 – 0. oral contraceptive use (never.17 (1.70 (0.47 – 0. and GL could be associated with factors such as socioeconomic status.24) 0.63–1.08 (0.61 (0.56) 0.63–1.16) 0.24) 0.12 (0. and ‡3). others have shown that GI values can be used to accurately predict the effect of mixed meals on blood glucose levels [44.87–1. however.05 (0.87–1.51 (1. college.original article Multivariate ORa by quartile of intake Q1 Q2 Q3 GI BMI (kg/m2) <25 ‡25 GL BMI (kg/m2) <25 ‡25 Total carbohydrates BMI (kg/m2) <25 ‡25 Total sugar BMI (kg/m2) <25 ‡25 Total starch BMI (kg/m2) <25 ‡25 BMI (kg/m2) Total fiber <25 ‡25 a Annals of Oncology Table 3.66) 0. and sugar intake and risk of ovarian cancer by body mass index (BMI) P for trend Q4 P for interaction 1.0 0. We assessed this issue by comparing data from our control group with data from the 2004 Australian National Health Survey (NHS) (a representative survey of the Australian adult population) [46]. parity (0.67–1.11 0.26 (0.73 (0.54) 1.05 (0.008 – 0. CO is supported by a grant from the Xstrata Community Partnership Program.20) 1. 45]. total carbohydrates. 1336 | Nagle et al. Despite these limitations.85 (0. These findings raise the possibility that adopting a low-GL high-fiber diet may result in small but potentially valuable reductions in the occurrence of ovarian cancer.00 (0.33) 1.93–1.84–1.79–1.88 0.90) 1.73–1. Army Medical Research and Materiel Command (grant no. the National Health and Medical Research Council of Australia to PW and CN. It is also likely that systematic error may be present due to underreporting of intakes within specific population subgroups. such as overweight women underreporting their sugar consumption. <60 months. Volume 22 | No. Australia.60–1.55–1.07 (0.10 (0.21 0. and 0. GI.63–1.09 – 0.S.16) 0.01–1.34 1.0 1. respectively.34 (1.39 Multivariate ORs and 95% CI adjusted for age.31) 1. energy intake (log transformed).88–1.40) 0.90–1.79–1. 1–2.02 (0. We believe that these findings warrant further investigation as potentially important modifiable exposures in investigations of risk of cancer and other chronic diseases.60–1. and university).46–0.80) 1.88 (0.68–1.56) 1. ORs and 95% CIs associated with GL. Estimating food and nutrients intakes by questionnaires is associated with measurement error and has been shown to attenuate effect estimates [43]. Another limitation of our study was the relatively low participation rate among controls (47%).15 (0.05 – 0.87) 0.32) 1. 2011 1.61 (1.72 0. parity.

21: 215–244. Am J Epidemiol 1999. 18. 149: 21–31. Howlett J.oxfordjournals. Kaaks R. Int J Cancer 2008. Insulin-like growth factor-1 and its receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines. Jain M. IGF-I. 13: 535–539. 93: 911–915.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25. Lundin E. 5. Tzonou A. 65: 1027–1033. 35. and Western Australia Cancer Registry. Negri E. 23. Am J Clin Nutr 2000. 4. Textbook of Cancer Epidemiology. Royal Hospital for Women. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. 31: 2281–2283. N. Marks GC. 18: 335–341. 3. Cancer 1994. 59: 92–96. 30. Connolly JM. Parsons. 21. Woods MN. Conover CA. SHBG. Nutrition 1997. Nagle CM. Lukanova A. 17. Khandwala HM. Augustin LS. North Shore Private Hospital. P. Implications for breast cancer prevention. Dietary factors and epithelial ovarian cancer. Lukanova A. Mercy Hospital For Women. Front Biosci 2003. 894). Am J Epidemiol 2009. and D. 287: 2414–2423. Risch HA. 69: 756–760. Gynecol Obstet Fertil 2001. Connolly JM. acknowledgements Full membership of the AOCS Group is listed at http:// www. Queen Elizabeth II. The glycemic index: physiological mechanisms relating to obesity. Cancer Causes Control 2002. The insulin-like growth factor/insulin system in epithelial ovarian cancer. Food properties affecting the digestion and absorption of carbohydrates.aocstudy. and New South Wales Cancer Registry. Downloaded from annonc. Green TJ. Talcum powder. Eur J Clin Nutr 2002. Howe GR et al. insulin and leptin in prostate cancer cases and controls. 26. 2. Lab Invest 1993. Howe GR. chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. Liljeberg H et al. Geneva. Dietary fiber intake and ovarian cancer risk: a prospective cohort study. Am J Epidemiol 1985. Monash Medical Centre. Effects of a very low fat. Franceschi S. Cancer 1995. Westmead Hospital. Augustin LS. Venn BJ. Reproducibility and validity of a semiquantitative food frequency questionnaire. Br J Cancer 1989. Western Australia: King Edward Memorial Hospital. Nutrient intake and ovarian cancer: an Italian case-control study. Diabetes Care 2008.org/. high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women. 2011 disclosure The authors have declared no conflict of interest. 59: 211–218. Jones C et al. Foster-Powell K. 86: 1409–1415. Micheli A et al. Kalli KR. Silvera SA. Folsom AR et al. Trichopoulos D. George SM. Bagga D. Whiteman. 2nd edition. Oxford. Royal Brisbane and Women’s Hospital. Diet and ovarian cancer risk: a casecontrol study in Italy. Cancer Causes Control 2007. Glycemic response and health—a systematic review and meta-analysis: relations between dietary glycemic properties and health outcomes. 19. and risk of cancer: a prospective cohort study. Stampfer MJ et al. Sampson L. and South Australian Cancer Registry. 15. Plasma insulin. Dietary glycemic index. Royal North Shore Hospital. Spiegelman DL et al. Dietary glycemic index. A prospective study of dietary glycemic load. 28. Validation of a food-frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: the method of triads model. McCutcheon IE. Dietary fat intake and risk of epithelial ovarian cancer. 31. Gaffney P et al. Montella M et al. Ann Oncol 2003. Ludwig DS. J Natl Cancer Inst 1994. 6. 13: 255–261. 32. Bosetti C et al. Hayward. St John of God Hospitals Subiaco. Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. glycemic load. Howe GR et al. carbohydrate intake. 10. 74: 1125–1131. Diet and ovarian cancer: a casecontrol study in Greece. Merritt MA.Annals of Oncology original article 14. Eur J Clin Nutr 2005. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Willett WC. Yuan JM et al. Victoria: Freemasons Hospital. Tasmania: Royal Hobart Hospital. Jain M. Eur J Cancer Prev 2003. Townsville Hospital. Rubin R. 169: 462–472. Rose DP. Kushi LH. and risk of coronary heart disease in US women. 20. Livesey G. Ambrose D. In WHO (ed): WHO Technical Report Series (no. glycaemic load and ovarian cancer risk: a prospective cohort study. McNaughton SA. Schaaf P. Kaaks R. 33. the Australian Cancer Study Investigators are A. 54: 520–525. 25. Interrelationships between plasma testosterone. Hsieh CC. Wesley Hospital. Atkinson FS. Taylor R. 56: 1049–1071. Webb PM. Kaaks R. Obesity: preventing and managing the global epidemic-report of a WHO consultation on obesity. Granfeldt Y. Mink PJ. 10: 1076–1081. 122: 170–176. Endocr Rev 2000. Webb.1093/annonc/mdq595 | 1337 . Willett W. Cancer Epidemiol Biomarkers Prev 2005. 12: 309–315. The effect of dietary fat and fiber on serum estrogen concentrations in premenopausal women under controlled dietary conditions. Int J Cancer 2004. Goldin BR. Parekh S. diabetes. Stampfer MJ et al. Glycaemic index. Int J Cancer 2001. Glycemic index and glycemic load: measurement issues and their effect on diet-disease relationships. and cardiovascular disease. Royal Adelaide Hospital. high fiber diet on serum hormones and menstrual function. Polesel J. Bjorck I. Polychronopoulou A et al. 7. Resnicoff M. Mallitt KA et al. Am J Clin Nutr 1994. 8. Public Health Nutr 2009. Leitzmann MF et al. Public Health Nutr 2007. 55: 411–414. and Queensland Cancer Registry. Strong LE. 27. 29: 185–191. Royal Prince Alfred Hospital. Marrett LD. glycemic load and ovarian cancer risk: a case-control study in Italy. Eur J Clin Nutr 2007. Hunter D. 8: d714–d722. Friend KE. Mayne ST. Adami H-O. 22. Hulshof T. South Australia: Flinders Medical Centre. Jenkins DJ et al. 12: 2359–2365. Liu S. 6 | June 2011 doi:10. Coppola D. Bidoli E. Jeppesen J. Royal Women’s Hospital. Lukanova A. Silvera SA. Goldman M. La Vecchia C. P. We acknowledge Maria Celia Hughes from the Queensland Institute of Medical Research for preparation of the dietary data and Nirmala Pandeya of the Queensland Institute of Medical Research for her statistical advice and would like to thank all the women who participated in the study. Prospective study of diet and ovarian cancer. 14: 98–107. 9. Western Australia Research Tissue Network. Green AC. 87: 258S–268S. Shu XO. JAMA 2002. Volume 22 | No. Int J Cancer 1993. Switzerland: World Health Organization 2000. Am J Clin Nutr 1991. 24. 34. UK: Oxford University Press 2008. 76: 2491–2496. Flyvbjerg A. Am J Clin Nutr 1997. Gao YT. Lubin M. Green. references 1. Franceschi S et al. Geffrey SP et al. Jain M. Effects of diet supplementation with wheat bran on serum estrogen levels in the follicular and luteal phases of the menstrual cycle. 11. 71: 1455–1461. Brand-Miller JC. Ibiebele TI. and Victorian Cancer Registry. 12. Am J Clin Nutr 2008. International tables of glycemic index and glycemic load values: 2008. IGF-I and breast cancer. Queensland: Mater Misericordiae Hospital. Glycemic index in chronic disease: a review. We gratefully acknowledge the support and assistance of the Survey of Women’s Health study research group and the cooperation of the following institutions: New South Wales: John Hunter Hospital. Bosetti C. World Health Organisation. 29. Rinaldi S et al. Rose DP. 122: 51–65. 61 (Suppl 1): S122–S131. Ashley JM. 108: 425–432. Sir Charles Gairdner Hospital. 59: 699S–705S. Reproducibility of food and nutrient intake estimates using a semi-quantitative FFQ in Australian adults. 14: 78–84. Effects of low-fat. 16. 13. High-fiber diet reduces serum estrogen concentrations in premenopausal women.

J Natl Cancer Inst 1983. Decarli A. 71: 681–686. Brand JC. Marshall J. and other personal characteristics. Annals of Oncology 42. A case-control study of dietary and nondietary factors in ovarian cancer. 41. 136: 459–465. National Health Survey. Do low control response rates always affect the findings? Assessments of smoking and obesity in two Australian casecontrol studies of cancer. Graham S et al. J Nutr 2003. 13: 1521–1527. Volume 22 | No. Freudenheim JL. Chatenoud L et al. Green AC et al. Reproductive and dietary risk factors for epithelial ovarian cancer in China. Zhang M. Williams GM. Chew I. 40. McCann SE. 92: 320–326. Binns CW. 4364. 6 | June 2011 . Canberra. Risk of human ovarian cancer is related to dietary intake of selected nutrients. 37: 2235–2239. Public Health Nutr 2002. 43. 126: 2798–2806. Am J Clin Nutr 1988. Pan SY. Int J Cancer 2008. phytochemicals and food groups. Lee AH. Cancer Epidemiol Biomarkers Prev 2004. 37. age. Downloaded from annonc. Eur J Cancer 2001. Mao Y et al. J Nutr 1996. Pandeya N. Edefonti V. Pelucchi C. Kipnis V.original article 36. 5: 915–923. Hughes MC. La Vecchia C et al. Nutrient dietary patterns and the risk of breast and ovarian cancers. Dietary fibres and ovarian cancer risk. Bolognesi C. Australia: Australian Bureau of Statistics 2006. 39. Truswell AS. La Vecchia C. 133: 1937–1942. J Nutr 2006. 47. Australian Bureau of Statistics. Byers T. 33: 312–319. Midthune D. Marshall JR. 44. Source and amount of carbohydrate affect postprandial glucose and insulin in normal subjects. van der Pols JC. 38. Thorburn AW.org at Funda??o Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior on May 25. Graham S. A case-control study of diet and the risk of ovarian cancer. Wolever TM. Ugnat AM. 46. 122: 609–613. Relative validity of food intake estimates using a food frequency questionnaire is associated with sex. Freedman L et al. 47: 53–56. 45.oxfordjournals. Application of glycemic index to mixed meals. Gynecol Oncol 2004. 2011 1338 | Nagle et al. Bias in dietary-report instruments and its implications for nutritional epidemiology. 2004-05 Vol Cat No. Marks GC. Aust N Z J Public Health 2009.