View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by ScholarsArchive@OSU IJC International Journal of Cancer Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial Gerd Bobe1,2, Gwen Murphy3, Paul S. Albert4, Leah B. Sansbury5, Elaine Lanza1, Arthur Schatzkin3 and Amanda J. Cross3 1 Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Frederick, MD 2 Linus Pauling Institute and Department of Animal Sciences, Oregon State University, Corvallis, OR 3 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), NCI, NIH, Rockville, MD 4 Biostatistics and Bioinformatics Branch, National Institute of Child Health and Human Development, NIH, Rockville, MD 5 Epidemiology and Genetics Research Program, Division of Cancer Control and Population Science, NCI, NIH, Rockville, MD Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest vs. lowest lignan intake quartile OR 5 2.07, 95% CI: 1.22–3.52, p trend 5 0.004) but not in men (p interaction 5 0.04). To conclude, dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women. Polyphenols have generated interest as components of fruits richest dietary sources of lignans are flax or linseed and ses- and vegetables that show cancer protective properties.1,2 On ame seed (3.5 g/kg).7 Beverages (wine, tea, coffee and orange the basis of their chemical structure, polyphenols are divided juice), cereals, bread, legumes, fruits (strawberries, peaches into subclasses, the most pertinent being tannins (proantho- and oranges) and vegetables (broccoli, squash and cabbage) cyanidins, hydrolysable tannins), lignans, stilbenes, phenolic are, despite having 100–1,000-fold lower lignan contents than acids and flavonoids.3 We previously showed that the flavonoid flax or sesame seed, the major dietary sources of lignans.8–11 subgroups flavonols and isoflavonoids and the flavan-3-ol epi- The antioxidative, anti-inflammatory and phytoestrogenic gallocatechin-3-gallate (EGCG) decrease the risk of advanced properties of lignans and their metabolites, as well as their adenoma recurrence in the Polyp Prevention Trial (PPT).4,5 ability to inhibit proliferation, invasion and angiogenesis and Lignans are diphenolic compounds present in the fibrous to promote apoptosis12–17 suggest a plausible role for them in portion of plants, which are (partially or fully) converted by chemoprevention of colorectal carcinogenesis. Results from microbial gut flora to enterolactone and enterodiol.6 The human studies are mixed with lignan consumption being associated with increased risk of colorectal cancer in a Cana- Key words: cancer prevention, colorectal adenoma, colorectal cancer, dian case-control study but a decreased risk in an English lignans, proanthocyanidins nested case-control study.11,18 The association between lignan Abbreviations: BMI: body mass index; CI: confidence interval; intake and colorectal cancer may differ between men and Epidemiology EGCG: epigallocatechin 3-gallate; FFQ: food frequency women, as sex modified the association between enterolac- questionnaire; IQR: interquartile range; NSAID: nonsteroidal anti- tone concentrations and colorectal cancer in both a Danish inflammatory drug; OR: odds ratio; PPT: Polyp Prevention Trial; and an English nested case-control study.18,19 Dietary fiber USDA: U.S. Department of Agriculture. and fat may modify the association between lignan intake Grant sponsor: Intramural Research Program, National Cancer and colorectal cancer by altering the intestinal microflora Institute, NIH, DHHS (Bethesda, MD) and, thus, the conversion of plant lignans to the more bioac- *Published 2011. This article is a US Government work and, as tive enterolactone and enterodiol20; as such, lignan intake such, is in the public domain of the United States of America. and enterolactone concentration produced opposing results DOI: 10.1002/ijc.26184 in relation to colorectal cancer in the English nested case- History: Received 3 Nov 2010; Accepted 21 Apr 2011; Online 26 control study.18 Furthermore, dietary lipids may alter the May 2011 effect of lignans on the metabolism of steroid hormones,6,21 Correspondence to: Gerd Bobe, 112 Withycombe Hall, Oregon which are involved in the etiology of colorectal tumorigene- State University, Corvallis, OR 97331, Tel: 541-737-1898, Fax: sis, as lignans and lipids are both involved in steroid hor- 541-737-4174, E-mail: [email protected] mone synthesis and metabolism. Int. J. Cancer: 130, 1649–1659 (2012) 2011 UICC 1650 Lignans, proanthocyanidins and adenoma recurrence Proanthocyanidins (e.g., condensed tannins) are polymers villous components, or showed high grade dysplasia were of elementary flavan-3-ol units and are common constituents classified as advanced adenomas. High risk adenoma recur- of U.S. diets.22–24 The main dietary sources of proanthocyani- rence was defined as having at least three pathologically con- dins are fruits (grapes, apples and plums), legumes (dry beans), firmed adenomas of any size or an advanced adenoma at T4. beverages (red wine, tea, cocoa and fruit juices) and choco- late.23,25,26 Their antioxidant, anti-mutagenic, anti-inflamma- Lignan and proanthocyanidin data tory and antimicrobial activity, along with their ability to At T0 and at each of the annual follow-up visits, participants chelate metal ions, proteins and toxins, promote apoptosis and completed a self-administered modified Block-National Cancer inhibit proliferation supports their role in chemoprevention of Institute Food Frequency Questionnaire (FFQ), which asked 22,27,28 colorectal cancer in animal and in vitro studies. The about the frequency of intake and portion size of 119 food results from human studies, however, are less convincing: a and beverage items during the past year.34,35 Some FFQ food Scottish and an Italian case-control study reported an inverse items were a single fruit or vegetable, such as apples, whereas association between proanthocyanidin intake and colorectal others were grouped food items, such as ‘‘other fruits,’’ which 29,30 cancer risk ; whereas another Scottish case-control study, as included grapes, plums and pineapples. Trained, certified well as the prospective Iowa Women’s Health Study reported 36 31,32 nutritionists reviewed all FFQs with participants. Compared no association with colorectal cancer. with 24-hr dietary recalls and four-day food record data, the The objective of our study was to prospectively evaluate FFQ slightly overestimated fat and underestimated fiber, fruit whether consumption of lignans and proanthocyandins, over- and vegetable intake and had acceptable correlations for fat all or stratified by gender and key dietary factors, was associ- (r ¼ 0.63), fibre (r ¼ 0.63), fruit and vegetable (r ¼ 0.72), dry ated with colorectal adenoma recurrence in the PPT. To our bean (r ¼ 0.76) and other macro- and micro-nutrients. With knowledge, this is the first study to prospectively evaluate respect to foods with available lignan data, the FFQ asked this relationship. three questions on legumes, one on nuts, 17 on vegetables (including soups), 11 on fruits, nine on breads/cereals, 13 on beverages and 11 on processed food consumption. The FFQ Material and methods did not specifically ask questions on intakes of flaxseed, linseed Study design and population or sesame seed, which are enriched in lignans, because these The PPT was a 4-year randomized, multi-center, nutritional were rarely consumed in the U.S. when the PPT was con- intervention trial to evaluate whether an intervention ducted. Lignan intake was estimated for 58 of 65 food and designed to encourage consumption of a high-fibre, high-fruit beverage items using a Canadian phytoestrogen database and and high-vegetable, and low-fat diet would decrease the risk was calculated as the sum of lariciresinol, matairesinol, pinore- of adenoma recurrence. Details of the study have been previ- 8 33–35 sinol and secoisolariciresinol. Three other phytoestrogen data- ously described. To be eligible for the study, participants 10,37,38 had at least one histologically confirmed colorectal adenoma bases were used for seven food items (brown or wild identified by complete colonoscopy in the 6 months before rice, brussel sprouts, chocolate candy, other vegetables, peas, study entry. Our study included 1,859 participants of the popcorn and spaghetti) not included in the Canadian database. control (n ¼ 930) and the intervention arm (n ¼ 929) that The four databases were similar in lignan concentrations of had a colonoscopy at baseline (T0) and at the end of the common foods and beverages. With respect