Diet and postmenopausal breast cancer - With a focus on low-grade inflammation

Sammanfattning: Diet-breast cancer studies have shown that “healthy eating patterns” are associated with decreased risk whereas unhealthy patterns (especially those including alcohol) are associated with increased risk, particularly in postmenopausal women. The potential mechanisms behind the observed associations are still under investigation. A great deal of evidence supports the major role of lifelong overexposure to sex hormones in the induction and progression of breast cancer, especially after menopause. However, this alone cannot fully explain the variation of breast cancer incidence across populations, and we hypothesize that an inflammatory environment, promoted by a Western lifestyle, may also play an important role. It is accepted that inflammation is an important feature in cancer development and progression, but also that cancer induces inflammatory processes.This thesis aimed to investigate the role of diet in the development of postmenopausal breast cancer, with a special interest in low-grade inflammation as a possible pathway. A population-based cohort, the Malmö Diet and Cancer (MDC) Study, consisting of 28,098 participants was used. The baseline examinations, that took place between 1991 and 1996, included blood sampling, anthropometric measurements and the detailed collection of dietary data.In study I, we inspected the reliability of several biomarkers of inflammation, examining a random sample of 95 people (46 women and 49 men) recruited from the MDC cohort. Six blood samples were taken at different occasions during a 6-week period in 2010-2011 (in fasting and non-fasting states). Intraclass correlation coefficients for the biomarkers were estimated. In study II, the association between diet quality and several inflammatory biomarkers was examined. A group of 667 individuals from the MDC-cardiovascular arm were randomly selected, and baseline data on diet and biomarkers of inflammation were investigated. Studies III and IV used a nested-case control design with 446 breast cancer cases and 910 matched controls. In study III, we analyzed the breast cancer risk associated with specific biomarkers and the possible role of obesity in this association. Finally, the association between dietary patterns derived to explain the variation of certain inflammation markers and breast cancer was explored in study IV.Our findings indicated a high reliability for the biomarkers of inflammation. Lower concentrations of biomarkers of inflammation were associated with higher diet quality, as assessed by overall adherence to the Swedish nutrition recommendations. We found three inflammation markers (ox-LDL, IL-1β and TNF-α) to be associated with breast cancer independent of obesity, but with diverging directions. We did not find evidence for inflammation-driven dietary patterns to be associated with breast cancer risk.In conclusion, an overall higher diet quality pattern was associated with lower inflammation. However, inflammation did not seem to explain possible associations between diet and postmenopausal breast cancer, as the dietary patterns identified to explain the variation in biomarkers of inflammation did not associate with breast cancer.