Vingrys, Kristina ORCID: https://orcid.org/0000-0002-2118-4254 (2020) Polyphenols and colorectal cancer. PhD thesis, Victoria University.

Abstract

Colorectal cancer (CRC) is an insidious disease that is often life-threatening, and places a significant burden on society and the individuals it affects. CRC is commonly called ‘bowel cancer’ and affects any part of the colon or the rectum. The effects of CRC not only increases risk of mortality but can severely impact a person’s physical functioning and quality of life. CRC has a complex, multifactorial aetiology, where diet is recognised as a modifiable risk factor. Several health benefits are recognised with consumption of grains and cereals, and in particular, wholegrains and dietary fibre are associated with strong evidence as protective factors in reducing CRC risk. Phenolic compounds (polyphenols) found in grains and cereal foods are major sources of antioxidants in the diet and may contribute to this protective role, via several anti-carcinogenic mechanisms related to CRC aetiology. CRC cellular and animal models suggest polyphenols may contribute to a protective role, however the associations are not as clear in humans. Polyphenols are broadly classified as flavonoids and non-flavonoids, however there is a lack of data for non-flavonoid compounds which are associated with grains and cereals. Moreover, there is a lack of data examining the association between polyphenol intakes and CRC risk in the Australian population. Therefore, the primary aim of this PhD project was to understand the association between dietary intake of polyphenols, particularly cereal-derived polyphenols, and CRC risk, via a systematic review and meta-analysis, in vitro studies and cohort studies. The first study (Chapter 3) analysed wheat, barley and sorghum grains, control and malted, as well as breakfast cereals made from raw and malted wheat and barley for total polyphenol content, radical scavenging activity and polyphenol profile. Analysis by Folin assay showed that malting increased total polyphenol content in all samples compared with controls, and radical scavenging activity against the free radical 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) increased in malted wheat breakfast cereals compared with control. The polyphenol profiles also showed diversity between the samples when quantified by HPLC. Grains and cereal foods were found to be good sources of polyphenol antioxidants and that malting induced additional polyphenols and antioxidant activity in grains and cereal products. The association between experimental findings and human CRC risk was subsequently investigated in the following chapters. The second study was a systematic review and meta-analysis of case-control and prospective studies that examined the association between dietary exposure to polyphenols and CRC risk (Chapter 4). Pooled analysis of summary estimates showed a reduction of CRC risk was associated with higher dietary intake of anthocyanins, flavones, flavonols, isoflavones, proanthocyanidins and lignans in case-control studies assessing exposure by dietary methods, however this was generally not reflected in prospective studies. This study highlighted that the effects of polyphenols associated with CRC risk were inconsistent between case-control and prospective studies, and that there was a lack of data for non-flavonoids or assessment by biomarkers. Importantly, this study also demonstrated that there was a lack of studies from Australia. The third study (Chapter 5) estimated the cereal-derived polyphenol intake in the Melbourne Collaborative Cohort Study (MCCS), a prospective cohort totalling 41,513 people. A purpose-built polyphenol database was matched to the dietary intakes of the eligible cohort (n = 39,892). This study revealed that phenolic acids, mainly ferulic acid, followed by alkylresorcinols, were the most prevalent compounds consumed in that cohort, with lignans making smaller contributions to dietary intakes from the cereals food group. New insights were gained about the intakes of cereal polyphenols, the limitations of indirect polyphenol intake assessment that are currently widely used, and future research opportunities were identified to improve current practice.

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