Abstract
Purpose: Advanced glycation end-products (AGE) are hypothesized to be involved in carcinogenesis. We analyzed dietary AGE intake in relation to invasive breast cancer (BC) to advance our knowledge of the impact of diet on BC risk.
Methods: Dietary AGE intake was estimated from the food-frequency questionnaire in postmenopausal women in the NIH AARP Diet and Health study, prospective cohort (n=183,548). Incident BC cases were identified through linkage with state cancer registries. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for developing BC according to quintiles of AGE levels. Multivariate regression models were adjusted for established BC risk factors.
Results: During a mean follow-up of 12.8 years, 9,851 BCs (1,978 advanced stage) were identified. Median daily AGE intake was 5,932 KU/1,000 kcal (10th- 90th percentile, 3,555 - 8,644). Women with higher AGE intake tended to have lower education level, higher BMI, younger age at menarche, menopause, first birth, more children, less physical activity, current smoking and higher total fat and meat intake. AGE intake was associated with increased risk of BC in the multivariate model 1, but the association was attenuated and no longer significant after adjusting for total meat and fat intakes (Table). The association between AGE intake and BC did not differ by BMI, hormone therapy use, or alcohol consumption. AGE intake was not related to BC hormone receptor status, histologic type, or grade. However, AGE intake was associated with increased risks of advanced stage tumors (highest vs. lowest quintile of AGE intake, RR 1.37 95% CI 1.09-1.74) even after controlling for total meat and fat intakes. The risk of advanced stage BC increased by 14% (RR 1.14 95% CI 1.04-1.25 in multivariate model 2) per 2,500 KU/1,000 kcal increase in AGE intake.
Conclusions: Dietary AGEs may play a role in the development of postmenopausal BC, particularly in advanced stage BC.
Quintiles of AGE intake | |||||||
1 | 2 | 3 | 4 | 5 | P value | Continuous AGE | |
Total invasive breast cancer | |||||||
No. of cases | 1,899 | 2,023 | 1,932 | 1,995 | 2,002 | ||
Age-adjusted model | 1 reference | 1.07 (1.01-1.14) | 1.03 (0.97-1.10) | 1.08 (1.01-1.15) | 1.10 (1.04-1.17) | .005 | 1.05 (1.02-1.07) |
Multivariate model 1 | 1 reference | 1.06 (0.99-1.13) | 1.01 (0.95-1.08) | 1.05 (0.99-1.12) | 1.09 (1.02-1.16) | .03 | 1.04 (1.02-1.07) |
Multivariate model 2 | 1 reference | 1.00 (0.93-1.08) | 0.94 (0.86-1.02) | 0.96 (0.88-1.06) | 1.00 (0.90-1.11) | .99 | 1.03 (0.99-1.08) |
Stage | |||||||
Localized | |||||||
No. of cases | 1,021 | 1,016 | 974 | 1,001 | 989 | ||
Age-adjusted model | 1 reference | 1.00 (0.92-1.09) | 0.97 (0.88-1.05) | 1.00 (0.92-1.09) | 1.01 (0.92-1.10) | .89 | 1.02 (0.99-1.06) |
Multivariate model 1 | 1 reference | 0.99 (0.90-1.08) | 0.95 (0.87-1.04) | 0.98 (0.90-1.07) | 1.00 (0.92-1.10) | .92 | 1.02 (0.98-1.06) |
Multivariate model 2 | 1 reference | 0.90 (0.81-0.99) | 0.84 (0.75-0.94) | 0.86 (0.76-0.98) | 0.90 (0.78-1.04) | .32 | 1.02 (0.96-1.09) |
Distant/Regional | |||||||
No. of cases | 341 | 414 | 377 | 408 | 438 | ||
Age-adjusted model | 1 reference | 1.22 (1.06-1.41) | 1.12 (0.97-1.29) | 1.22 (1.05-1.41) | 1.33 (1.15-1.53) | <.001 | 1.11 (1.05-1.17) |
Multivariate model 1 | 1 reference | 1.21 (1.04-1.39) | 1.10 (0.94-1.27) | 1.18 (1.02-1.37) | 1.28 (1.11-1.48) | .004 | 1.09 (1.03-1.16) |
Multivariate model 2 | 1 reference | 1.25 (1.06-1.47) | 1.15 (0.95-1.40) | 1.25 (1.02-1.54) | 1.37 (1.09-1.74) | .02 | 1.14 (1.04-1.25) |
Quintiles of AGE intake | |||||||
1 | 2 | 3 | 4 | 5 | P value | Continuous AGE | |
Total invasive breast cancer | |||||||
No. of cases | 1,899 | 2,023 | 1,932 | 1,995 | 2,002 | ||
Age-adjusted model | 1 reference | 1.07 (1.01-1.14) | 1.03 (0.97-1.10) | 1.08 (1.01-1.15) | 1.10 (1.04-1.17) | .005 | 1.05 (1.02-1.07) |
Multivariate model 1 | 1 reference | 1.06 (0.99-1.13) | 1.01 (0.95-1.08) | 1.05 (0.99-1.12) | 1.09 (1.02-1.16) | .03 | 1.04 (1.02-1.07) |
Multivariate model 2 | 1 reference | 1.00 (0.93-1.08) | 0.94 (0.86-1.02) | 0.96 (0.88-1.06) | 1.00 (0.90-1.11) | .99 | 1.03 (0.99-1.08) |
Stage | |||||||
Localized | |||||||
No. of cases | 1,021 | 1,016 | 974 | 1,001 | 989 | ||
Age-adjusted model | 1 reference | 1.00 (0.92-1.09) | 0.97 (0.88-1.05) | 1.00 (0.92-1.09) | 1.01 (0.92-1.10) | .89 | 1.02 (0.99-1.06) |
Multivariate model 1 | 1 reference | 0.99 (0.90-1.08) | 0.95 (0.87-1.04) | 0.98 (0.90-1.07) | 1.00 (0.92-1.10) | .92 | 1.02 (0.98-1.06) |
Multivariate model 2 | 1 reference | 0.90 (0.81-0.99) | 0.84 (0.75-0.94) | 0.86 (0.76-0.98) | 0.90 (0.78-1.04) | .32 | 1.02 (0.96-1.09) |
Distant/Regional | |||||||
No. of cases | 341 | 414 | 377 | 408 | 438 | ||
Age-adjusted model | 1 reference | 1.22 (1.06-1.41) | 1.12 (0.97-1.29) | 1.22 (1.05-1.41) | 1.33 (1.15-1.53) | <.001 | 1.11 (1.05-1.17) |
Multivariate model 1 | 1 reference | 1.21 (1.04-1.39) | 1.10 (0.94-1.27) | 1.18 (1.02-1.37) | 1.28 (1.11-1.48) | .004 | 1.09 (1.03-1.16) |
Multivariate model 2 | 1 reference | 1.25 (1.06-1.47) | 1.15 (0.95-1.40) | 1.25 (1.02-1.54) | 1.37 (1.09-1.74) | .02 | 1.14 (1.04-1.25) |
Citation Format: Lindsay L. Peterson, Seho Park, Yikyung Park, Narges Anbardar, David Turner. Dietary advanced glycation end-products and postmenopausal breast cancer risk in the NIH AARP diet and health study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 619.