-
1.
Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
-
-
-
Free full text
-
Plain language summary
Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
-
2.
Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.
Vichos, T, Rezaie, A, Vichos, P, Cash, B, Pimentel, M
Digestive diseases and sciences. 2023;68(6):2585-2596
-
-
-
Free full text
-
Plain language summary
Colorectal cancer (CRC) is one of the most common cancers and adenomatous colorectal polyps (CRP) are a risk factor for developing CRC. The potential role of functional disturbances seen in irritable bowel syndrome (IBS) for the development of CRC are not yet clear. The aim of this systematic review and meta-analysis was to evaluate the occurrence of CRC and CRP in IBS patients. 14 cohort studies with a total of 654,764 IBS patients and 2,277,195 controls and six cross-sectional studies with 26,641 IBS patients and 87,803 controls were included in the review. Based on the pooled data from 5 cross-sectional studies, IBS patients had a significantly lower occurrence of CRP (by 71%). CRC risk was also reduced but this did not reach statistical significance. Only four of the 14 cohort studies were included in the meta-analysis and, again, CRC risk was lower in IBS patients but this was not statistically significant.
Abstract
OBJECTIVES Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.
-
3.
The Human Vulvar Microbiome: A Systematic Review.
Pagan, L, Ederveen, RAM, Huisman, BW, Schoones, JW, Zwittink, RD, Schuren, FHJ, Rissmann, R, Piek, JMJ, van Poelgeest, MIE
Microorganisms. 2021;9(12)
-
-
-
Free full text
Plain language summary
Vaginal microbiome composition and its link with cancer is an emerging area in research. Imbalances in the vaginal microbiome could initiate carcinogenesis by altering immunity and metabolism and accelerating inflammation. This systematic review included ten studies and assessed the vulvar microbiome in premalignant vulvar disease and healthy vulvar skin. The healthy vulvar skin showed several bacterial taxa of Lactobacillus, Corynebacterium, Staphylococcus and Prevotella of intestinal, cutaneous and vaginal origin. L. crispatus and L. iners were dominant on the vulva of most healthy women. L. gasseri dominance was non-significantly associated with vestibulodynia. Menstruation did not alter the bacterial composition. Premenarchial Lichen sclerosus may have an association with microbial dysbiosis. Further robust studies are required to identify the vaginal microbial composition due to the high heterogeneity of the studies included, small sample size and methodological limitations. Healthcare professionals can utilise the data from this study to better understand how the vulvar microbiome influences disease aetiology and its importance as a target for therapy.
Abstract
The link between cancer and the microbiome is a fast-moving field in research. There is little knowledge on the microbiome in ((pre)malignant) conditions of the vulvar skin. This systematic review aims to provide an overview of the literature regarding the microbiome composition of the healthy vulvar skin and in (pre)malignant vulvar disease. This study was performed according to the PRISMA guidelines. A comprehensive, electronic search strategy was used to identify original research articles (updated September 2021). The inclusion criteria were articles using culture-independent methods for microbiome profiling of the vulvar region. Ten articles were included. The bacterial composition of the vulva consists of several genera including Lactobacillus, Corynebacterium, Staphylococcus and Prevotella, suggesting that the vulvar microbiome composition shows similarities with the corresponding vaginal milieu. However, the vulvar microbiome generally displayed higher diversity with commensals of cutaneous and fecal origin. This is the first systematic review that investigates the relationship between microbiome and vulvar (pre)malignant disease. There are limited data and the level of evidence is low with limitations in study size, population diversity and methodology. Nevertheless, the vulvar microbiome represents a promising field for exploring potential links for disease etiology and targets for therapy.
-
4.
The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-γ and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial.
Pirouzpanah, S, Asemani, S, Shayanfar, A, Baradaran, B, Montazeri, V
BMC complementary and alternative medicine. 2019;19(1):324
-
-
-
Free full text
Plain language summary
Individuals diagnosed with benign breast disease (BBD) are at an increased risk of developing breast cancer. A hormone known as insulin-like growth factor-1 (IGF-1) has been reported to correlate with the development of BBD into breast cancer. Berberis vulgaris (BV) is a herbal plant, which may have anti-cancer properties. Previous studies have reported alterations in proteins involved in tumour growth upon regular consumption, but none have looked at IGF-1 in individuals with BBD. This randomised double-blind trial aimed to study the effects of BV on IGF-1 and other proteins involved in tumour growth in 85 women recently diagnosed with BBD over an 8-week period. The results showed that compliance to BV treatment was high. IGF-1 significantly decreased within both groups. When compared to each other, there was a 16% drop in IGF-1 in the BV group compared to the placebo group. Several proteins and growth factors were also altered by BV treatment in favour of reducing breast cancer risk. The authors concluded that BV juice may reduce the risk of BBD turning into breast cancer. Clinicians could use this study to recommend regular consumption of BV to individuals with BBD as part of a wellness regime to reduce their risk of developing breast cancer.
Abstract
BACKGROUND The present study was designed to investigate the effects of Berberis vulgaris (BV) juice consumption on plasma levels of insulin-like growth factor (IGF-1), IGF-binding proteins (IGFBPs), and the expression of PPAR-γ, VEGF and HIF in women with benign breast disease. METHODS This parallel design randomized, double-blind controlled clinical trial was conducted on 85 eligible patients diagnosed with benign breast disease. They were assigned randomly into either BV juice group (n = 44, BV juice: 480 ml/day) or placebo group (n = 41, BV placebo juice: 480 ml/day) for 8 weeks intervention. Participants, caregivers and those who assessed laboratory analyses were blinded to the assignments. Plasma levels of biomarkers were measured at baseline and after 8 weeks by ELISA. Quantitative real-time PCR was used to measure the fold change in the expression of each interested gene. RESULTS The compliance of participants was 95.2% and 40 available subjects analyzed in each group at last. Relative treatment (RT) effects for BV juice caused 16% fall in IGF-1 concentration and 37% reduction in the ratio of IGF-1/1GFBP1. Absolute treatment effect expressed 111 ng/ml increased mean differences of IGFBP-3 between BV group and placebo. Plasma level of PPAR-γ increased in both groups but it was not significant. Fold changes in the expressions of PPAR-γ, VEGF and HIF showed down-regulation in the intervention group compared to placebos (P < 0.05). CONCLUSIONS The BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD. The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis. TRIAL REGISTRATION IRCT2012110511335N2. Registered 10 July 2013 (retrospectively registered).
-
5.
Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance.
Cotte, AK, Aires, V, Fredon, M, Limagne, E, Derangère, V, Thibaudin, M, Humblin, E, Scagliarini, A, de Barros, JP, Hillon, P, et al
Nature communications. 2018;9(1):322
-
-
-
Free full text
Plain language summary
Lipid droplet (LD) accumulation has been observed in an increasing number of cancer cell lines and is now a well-recognised hallmark of cancer. While the significance of LD accumulation remains unclear, recent studies have suggested it plays a role in tumour cell chemoresistance mechanisms. This study aims to fill in the gaps in the literature regarding LD formation and function under chemotherapy conditions in colorectal cancer cell models. For the first time, this study demonstrates a pertinent mechanism linking LD accumulation and resistance to conventional chemotherapies. The authors found that LD production is driven by the enzyme lysophosphatidylcholine acyltransferase 2 (LPCAT2), and that chemotherapy can trigger LD production, promoting chemoresistance. The authors conclude these findings could be useful for both prognostic factors as well as predictive factors for the patient’s responsiveness to conventional therapies.
Abstract
Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance of LD accumulation in colorectal cancer (CRC) biology is incompletely understood under chemotherapeutic conditions. Since drug resistance is a major obstacle to treatment success, we sought to determine the contribution of LD accumulation to chemotherapy resistance in CRC. Here we show that LD content of CRC cells positively correlates with the expression of lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme supporting phosphatidylcholine synthesis. We also demonstrate that LD accumulation drives cell-death resistance to 5-fluorouracil and oxaliplatin treatments both in vitro and in vivo. Mechanistically, LD accumulation impairs caspase cascade activation and ER stress responses. Notably, droplet accumulation is associated with a reduction in immunogenic cell death and CD8+ T cell infiltration in mouse tumour grafts and metastatic tumours of CRC patients. Collectively our findings highlight LPCAT2-mediated LD accumulation as a druggable mechanism to restore CRC cell sensitivity.
-
6.
Hypothesis and data-driven dietary patterns and colorectal Cancer survival: findings from Newfoundland and Labrador colorectal Cancer cohort.
Sharma, I, Roebothan, B, Zhu, Y, Woodrow, J, Parfrey, PS, Mclaughlin, JR, Wang, PP
Nutrition journal. 2018;17(1):55
-
-
-
Free full text
Plain language summary
Diet and lifestyle play a role in the risk and outcome of chronic diseases including colorectal cancer (CRC). This prospective follow-up study looked at the association between different dietary patterns and the risk of death and cancer recurrence in people with CRC. Over 500 CRC patients diagnosed between 1999 and 2003 were followed-up until 2010. Participants completed a food frequency questionnaire based on their diet a year prior to diagnosis, and this was used to identify several dietary patterns. Diets that were high in processed meats (HR 1.82), meat and dairy products (HR 2.19), and total grains, sugar and soft drinks (HR 1.95) were associated with a higher risk of mortality, cancer recurrence or metastasis. Poor adherence to a Mediterranean-style diet increased the risk of overall mortality (HR 1.62). Prudent vegetable, high sugar pattern, Recommended Food Scores and Dietary Inflammatory Index had no significant association with either mortality or combined mortality, recurrence or metastasis. The authors concluded that the risk of mortality, recurrence and metastasis in patients with colorectal cancer varies with different dietary patterns.
Abstract
BACKGROUND Dietary patterns are commonly used in epidemiological research, yet there have been few studies assessing if and how research results may vary across dietary patterns. This study aimed to estimate the risk of mortality/recurrence/metastasis using different dietary patterns and comparison amongst the patterns. METHODS Dietary patterns were identified by Cluster Analysis (CA), Principal Component Analysis (PCA), Alternate Mediterranean Diet score (altMED), Recommended Food Score (RFS) and Dietary Inflammatory Index (DII) scores using a 169-item food frequency questionnaire. Five hundred thirty-two colorectal cancer patients diagnosed between 1999 and 2003 in Newfoundland were followed-up until 2010. Overall Mortality (OM) and combined Mortality, Recurrence or Metastasis (cMRM) were identified. Comparisons were made with adjusted Cox proportional Hazards Ratios (HRs), correlation coefficients and the distributions of individuals in defined clusters by quartiles of factor and index scores. RESULTS One hundred and seventy cases died from all causes and 29 had a cancer recurrence/metastasis during follow-up. Processed meats as classified by PCA (HR 1.82; 95% confidence interval (CI) 1.07-3.09), clusters characterized by meat and dairy products (HR 2.19; 95% CI 1.03-4.67) and total grains, sugar, soft drinks (HR 1.95; 95% CI 1.13-3.37) were associated with a higher risk of cMRM. Poor adherence to AltMED increased the risk of all-cause OM (HR 1.62; 95% CI 1.04-2.56). Prudent vegetable, high sugar pattern, RFS and DII had no significant association with both OM and cMRM. CONCLUSION Estimation of OM and cMRM varied across dietary patterns which is attributed to the differences in the foundation of each pattern.
-
7.
Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention.
Dieli-Conwright, CM, Parmentier, JH, Sami, N, Lee, K, Spicer, D, Mack, WJ, Sattler, F, Mittelman, SD
Breast cancer research and treatment. 2018;168(1):147-157
-
-
-
Free full text
-
Plain language summary
Obese breast cancer patients have double the mortality compared to non-obese patients. This is thought to be mediated by low grade inflammation of the adipose (fat) tissue. The main type of immune cells involved in the process are called adipose tissue macrophages (ATMs), of which there are two types: M1 and M2 ATMs, with the M2 ATMs having a mostly anti-inflammatory effect, whilst the M1 ATMs are more pro-inflammatory and are thought to promote cancer growth and recurrence. This 16-week randomised pilot study assessed whether exercise can positively influence adipose tissue inflammation in breast cancer survivors. Participants were randomised to either an exercise (EX) group, who had three supervised exercise sessions per week with a combination of aerobic and resistance exercise, or a control (CON) group. Outcome measures included body composition, blood biomarkers for systemic inflammation and adipose tissue biopsies which were analysed for tissue inflammatory markers, including M1 and M2 ATMs. The EX group had significant improvements in body weight and composition, as well as in metabolic blood parameters (including those for lipid and glucose metabolism) and inflammatory markers, whilst the CON group experienced a worsening of these parameters. The EX participants also had a decrease in the pro-inflammatory M1 ATMs and an increase in the anti-inflammatory M2 ATMs. The authors state that the results were not only statistically, but also clinically significant. The authors conclude that moderate-to-vigorous intensity resistance and aerobic exercise can improve adipose tissue inflammation in obese breast cancer survivors.
Abstract
PURPOSE Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors. METHODS Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period. RESULTS EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p < 0.03 vs. CON). Adipose tissue from EX participants showed a significant decrease in ATM M1 (p < 0.001), an increase in ATM M2 (p < 0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and TNF- α (all p < 0.055). CONCLUSIONS A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.
-
8.
Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer.
Demark-Wahnefried, W, Rais-Bahrami, S, Desmond, RA, Gordetsky, JB, Hunter, GR, Yang, ES, Azrad, M, Frugé, AD, Tsuruta, Y, Norian, LA, et al
British journal of cancer. 2017;117(9):1303-1313
-
-
-
Free full text
-
Plain language summary
Obesity is a risk factor for 13 different cancers and a recent meta-analysis has shown increased weight to be associated with biochemical recurrence in men with prostate cancer. However, few studies have explored whether presurgical intentional weight loss results in improved prostate cancer outcomes. The aim of this trial was to explore the efficacy of weight loss among overweight and obese men with prostate cancer. Forty participants were randomised to either the presurgical weight loss intervention group or control arm, and changes in weight, body composition, quality of life, tumour biology and biomarkers were recorded. This study found that intentional weight loss caused mixed effects on tumour proliferation and gene expression. Based on these results, the authors recommend that more research is needed before effectively recommending presurgical weight loss among overweight men with prostate cancer.
Abstract
BACKGROUND Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. METHODS This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. RESULTS The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P=0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs -1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P=0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. CONCLUSIONS Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.
-
9.
Fish consumption and markers of colorectal cancer risk: a multicenter randomized controlled trial.
Pot, GK, Majsak-Newman, G, Geelen, A, Harvey, LJ, Nagengast, FM, Witteman, BJ, van de Meeberg, PC, Timmer, R, Tan, A, Wahab, PJ, et al
The American journal of clinical nutrition. 2009;90(2):354-61
-
-
-
Free full text
-
Plain language summary
Colorectal cancer (CC) risk is strongly related to dietary habits, with 65–75% of the incidence of CC attributed to dietary factors. This RCT studied the effects of fish consumption on markers of CC risk. 242 patients, either at high risk of developing CC or with a healthy bowel, were randomly assigned to 3 groups - 2 portions of oily fish per week, 2 portions of lean fish per week, or a control group who received dietary advice only for 6 months. 216 patients completed the trail. No statistically significant effect on CC risk markers was found between the fish groups and controls at 6 months. These results did not support the hypothesis that additional fish consumption over a 6-month period changes the number of colonic precancerous cells. The authors call for further studies to include non-fish eaters to further test their hypothesis.
Abstract
BACKGROUND Diet is a major factor in the etiology of colorectal cancer, with high fish consumption possibly decreasing colorectal cancer risk, as was shown in several observational studies. To date, no intervention trials have examined the possible beneficial effects of fish intake on colorectal cancer risk. OBJECTIVE The objective was to investigate the effects of a 6-mo intervention with oil-rich or lean fish on apoptosis and mitosis within the colonic crypt. DESIGN In a multicenter, randomized, controlled intervention trial, patients with colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease were recruited (n = 242) and randomly allocated to receive dietary advice plus either 300 g oil-rich fish (salmon) per week (n = 82), 300 g lean fish (cod) per week (n = 78), or only dietary advice (DA) (n = 82). Apoptosis and mitosis were measured in colonic biopsy samples collected before and after intervention (n = 213). RESULTS The total number of apoptotic cells per crypt did not increase in the salmon or cod group: -0.10 (95% CI: -0.36, 0.16) and -0.06 (95% CI: -0.32, 0.20), respectively, compared with the DA group. The total number of mitotic cells per crypt decreased nonsignificantly in the salmon group (-0.87; 95% CI: -2.41, 0.68) and in the cod group (-1.04; 95% CI: -2.62, 0.53) compared with the DA group. Furthermore, the distribution of mitosis within the crypt did not significantly change in either group. CONCLUSION An increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6 mo does not markedly change apoptotic and mitotic rates in the colonic mucosa. This trial was registered at www.clinicaltrials.gov as NCT00145015.
-
10.
Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer.
Thompson, LU, Chen, JM, Li, T, Strasser-Weippl, K, Goss, PE
Clinical cancer research : an official journal of the American Association for Cancer Research. 2005;11(10):3828-35
-
-
-
Plain language summary
High levels of the hormone oestrogen are linked with an increased risk of developing breast cancer. Plant lignans have similar chemical structures to oestrogen and may block the action of oestrogen in breast cancer cells. Flaxseed (also known as linseed) is a rich source of lignan precursors and has been shown to reduce tumour growth in rats. Therefore, it is thought that flaxseed might be effective in cancer treatment and prevention. This randomised, double-blind, placebo-controlled trial examined the effects of dietary flaxseed on tumour growth in postmenopausal women with newly diagnosed breast cancer. Patients were given either a muffin containing 25g of flaxseed or a control muffin, every day from the time of the initial biopsy until undergoing surgery to remove the tumours. They continued to eat their normal diet. The group that ate the flaxseed muffins experienced significant reductions of between 34 and 71% in various markers of tumour growth, and a significant increase in apoptosis of 30%. The control group did not experience any significant changes in these markers. The authors concluded that eating flaxseed has the potential to reduce tumour growth in patients with breast cancer.
Abstract
PURPOSE Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer. EXPERIMENTAL DESIGN Patients were randomized to daily intake of either a 25 g flaxseed-containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four-hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively. RESULTS Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = -0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). CONCLUSION Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.