Plant foods, plasma enterolactone and breast cancer - with a focus on estrogen receptor status and genetic variation

Sammanfattning: Diets high in fibre have previously been associated with decreased risk of breast cancer in the Malmö Diet and Cancer cohort. Several potent compounds may exist in high-fibre diets that might protect against breast cancer, for example lignans. Plant lignans are converted to enterolactone by the gut microflora and are similar in structure to estrogens. Enterolactone may interact with the estrogen receptors (ERs) and, therefore, inhibit the effect of estrogens. The aim of this doctoral project was to prospectively examine if plant food intakes and enterolactone blood concentrations were associated with breast cancer, and to examine if the association differed depending on ER status of the tumours or variation in the ER genes. Information (including high validity dietary data) from the Malmö Diet and Cancer cohort with baseline examinations from 1991 to 1996 was used. Among 15,773 women, 45-73 years at baseline, without prevalent cancer, 544 women were diagnosed with breast cancer until 31 December 2004. High intakes of high-fibre bread were associated with decreased risk of breast cancer. When restricting the analyses to individuals with suggested more stable food habits, a decreased breast cancer risk were also observed with high intakes of fruit, berries and vegetables. High-fibre bread and fruit and berries were the main dietary determinants of enterolactone concentration. In addition, obesity and smoking was associated with lower enterolactone concentrations. High enterolactone concentrations (>16 nmol/L) was associated with decreased breast cancer risk. When stratifying for fibre intake, a decreased breast cancer risk with high enterolactone concentration was only observed among individuals with high fibre intakes. Relatively high variation of enterolactone within and between individuals was observed; the association between enterolactone and risk of breast cancer is likely attenuated. The reduced breast cancer risk with high enterolactone concentrations was only observed for ER?-positive and ER?-negative tumours. Breast cancer risk was not significantly associated with any of the selected polymorphisms in the ER? and ER? genes. However, the protective effect of high enterolactone concentration was seen in subgroups of the individuals with specific genetic variants, and a tendency towards an interaction between a polymorphism in intron 3 of the ER? gene and enterolactone concentrations was observed. In conclusion, a high-fibre diet including high-fibre bread, fruit, berries and vegetables will likely reduce the risk of breast cancer in middle aged and older women. The protective effect of a high-fibre diet might be due to its content of lignans.