Lifestyle predictors for inconsistent participation to fecal based colorectal cancer screening.

BACKGROUND: Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening. METHOD: We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations). RESULTS: Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p < 0.05). CONCLUSIONS: Lifestyle behaviors were associated with inconsistent participation in FIT-screening. Initiatives aimed at increasing participation rates among those with the unhealthiest lifestyle have a potential to improve the efficiency of screening.

Associations of red and processed meat intake with screen-detected colorectal lesions.

Limited data exist regarding the role of meat consumption in early-stage colorectal carcinogenesis. We examined associations of red and processed meat intake with screen-detected colorectal lesions in immunochemical fecal occult blood test (FIT)-positive participants, enrolled in the Norwegian CRCbiome study during 2017-2021, aged 55-77 years. Absolute and energy-adjusted intakes of red and processed meat (combined and individually) were assessed using a validated, semi-quantitative FFQ. Associations between meat intake and screen-detected colorectal lesions were examined using multinomial logistic regression analyses with adjustment for key covariates. Of 1162 participants, 319 presented with advanced colorectal lesions at colonoscopy. High v. low energy-adjusted intakes of red and processed meat combined, as well as red meat alone, were borderline to significantly positively associated with advanced colorectal lesions (OR of 1·24 (95 % CI 0·98, 1·57) and 1·34 (95 % CI 1·07, 1·69), respectively). A significant dose-response relationship was also observed for absolute intake levels (OR of 1·32 (95 % CI 1·09, 1·60) per 100 g/d increase in red and processed meat). For processed meat, no association was observed between energy-adjusted intakes and advanced colorectal lesions. A significant positive association was, however, observed for participants with absolute intake levels ≥ 100 v. < 50 g/d (OR of 1·19 (95 % CI 1·09, 1·31)). In summary, high intakes of red and processed meat were associated with presence of advanced colorectal lesions at colonoscopy in FIT-positive participants. The study demonstrates a potential role of dietary data to improve the performance of FIT-based screening.

Plasma sex hormones and risk of conventional and serrated precursors of colorectal cancer in postmenopausal women.

BACKGROUND: Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. METHODS: We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. RESULTS: During 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17-1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02-2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99-1.78, P for trend = 0.03, respectively). CONCLUSIONS: The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.

BACKGROUND: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. METHODS: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. DISCUSSION: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538550 .

Should calculation of chemotherapy dosage for bowel cancer be based on body composition? / Bør beregning av cellegiftdose ved tarmkreft baseres på kroppssammensetning?

BACKGROUND: Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. MATERIAL AND METHOD: We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. RESULTS: Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. INTERPRETATION: The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number.

Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses' Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility variants. Associations of body shape trajectories and GRS with dichotomized TL and mtCN were assessed by logistic regression models. After adjustment for lifestyle and dietary factors, compared with the lean-stable group, the lean-marked increase group had higher odds of having below-median TL (OR = 1.18, 95% CI 1.04, 1.35; P = 0.01), and the medium-marked increase group had higher odds of having below-median mtCN (OR = 1.28, 95% CI 1.00, 1.64; P = 0.047). There was a suggestive trend toward lower mtCN across the GRS quartiles (P for trend = 0.07). In conclusion, telomere attrition may be accelerated by marked weight gain in middle life, whereas mtCN is likely to be reduced persistently by adiposity over the life course. The findings indicate the importance of lifetime weight management to preserve functional telomeres and mitochondria.

The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

BACKGROUND: Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. METHODS/DESIGN: This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. DISCUSSION: The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01570010 .

[Lipid profile of healthy persons with low-carbohydrate diet]. / Lipidprofil ved lavkarbokosthold hos friske.

BACKGROUND: Many Norwegians have embraced the low-carb trend and choose butter and bacon instead of brown bread and carrots. This entails a dramatic change in the total intake of fat and the intake of saturated fat. We have investigated how a low-carb diet can affect the lipid profile in healthy adults with a normal bodyweight. MATERIAL AND METHOD: Seven healthy female participants with normal bodyweight underwent a four-week trial of a low-carb diet (< 20-25 grams of carbohydrates/day). Daily diet registrations were made during the trial period, and diet data for three randomly selected days were included in the estimates. Blood samples and weight data were collected as fasting values prior to and after the intervention. RESULTS: Standardised diet data were available for six participants. On a low-carb diet, the energy intake from carbohydrates accounted for a median of 3 (spread: 2-5) per cent of the total energy intake. The intake of fat accounted for 71 (67-78) per cent of total energy, while protein accounted for 26 (19-31) of total energy intake. At baseline, the median value of total cholesterol was 4.1 mmol/L (dispersion: 3.3-5.7) and LDL cholesterol was 2.2 (1.8-3.4) mmol/L. The values increased to 5.2 (3.7-8.8) mmol/L and 3.1 (1.9-6.2) mmol/L for total and LDL cholesterol respectively. The absolute changes correspond to a percentage increase in total cholesterol of 33 (14-71)% and in LDL cholesterol of 41 (9-84)%. Median weight change amounted to -1.2 kg (-2.8-0.6). INTERPRETATION: A diet with little carbohydrate and a great deal of protein and fat resulted in a considerably heightened level of total cholesterol and LDL cholesterol in young, healthy women with a normal bodyweight. The findings indicate that a low-carb diet may have a negative impact on individual risk profiles. However, the study is small-scale and the results must be interpreted with caution.

Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis.

BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.

Agreement between GLIM and PG-SGA for diagnosis of malnutrition depends on the screening tool used in GLIM.

BACKGROUND & AIM: The Global Leadership Initiative on Malnutrition (GLIM) has suggested a process for the diagnosis of malnutrition. The process consists of applying an existing screening tool for malnutrition screening, followed by malnutrition diagnostics, and finally categorization of malnutrition severity (moderate or severe) according to specific GLIM criteria. However, it is not known how well the GLIM process agrees with other diagnostic tools used in the current clinical practice. The aim of this study was to validate the GLIM process against the Patient Generated-Subjective Global Assessment (PG-SGA) when different screening tools were applied in the screening step of the GLIM process. METHODS: Colorectal cancer (CRC) patients from the ongoing CRC-NORDIET study were included. For the GLIM process, the patients were first screened for malnutrition using either 1) Nutritional risk screening, first 4 questions (NRS-2002-4Q), 2) Malnutrition Screening Tool (MST), 3) Malnutrition Universal Screening Tool (MUST) or 4) the PG-SGA short form (PG-SGA-SF). The GLIM malnutrition diagnosis was then based on combining the result from each of the screening methods with the etiological and phenotypic GLIM-criteria including weight loss, BMI and fat free mass. In parallel, the patients were diagnosed using the PG-SGA methodology categorizing the patients into either A: well nourished, B: moderately malnourished or C: severely malnourished. The four different GLIM based diagnoses were then validated against the diagnosis obtained by the PG-SGA tool. Sensitivity, specificity and positive predictive value (PPV) were calculated to evaluate validity. RESULTS: In total, 426 patients were included (mean age: 66, ±8 years) at a mean time of 166 (±56) days after surgery. The GLIM diagnosis based on the four different screening tools identified 10-24% of the patients to be malnourished, of which 3-8% were severely malnourished. The PG-SGA method categorized 15% as moderately malnourished (PG-SGA: category B) and no patients as severely malnourished (PG-SGA: category C). The agreement between the PG-SGA and GLIM process was in general low, but differed according to the tools: PG-SGA SF (sensitivity 47%, PPV 71%), MST (sensitivity 56%, PPV 47%), NRS-2002-4Q (sensitivity 63%, PPV 53%) and MUST (sensitivity 53%, PPV 34%). CONCLUSION: In this cross-sectional study of patients with CRC, the concordance between the GLIM-criteria and PG-SGA depended on the screening tool used in the GLIM process. Malnutrition frequency based on the GLIM process schould be reported with and without the use of a screening tool.

Quantification of adipose tissues by Dual-Energy X-Ray Absorptiometry and Computed Tomography in colorectal cancer patients.

BACKGROUND & AIMS: Excess adipose tissue may affect colorectal cancer (CRC) patients' disease progression and treatment. In contrast to the commonly used anthropometric measurements, Dual-Energy X-Ray Absorptiometry (DXA) and Computed Tomography (CT) can differentiate adipose tissues. However, these modalities are rarely used in the clinic despite providing high-quality estimates. This study aimed to compare DXA's measurement of abdominal visceral adipose tissue (VAT) and fat mass (FM) against a corresponding volume by CT in a CRC population. Secondly, we aimed to identify the best single lumbar CT slice for abdominal VAT. Lastly, we investigated the associations between anthropometric measurements and VAT estimated by DXA and CT. METHODS: Non-metastatic CRC patients between 50-80 years from the ongoing randomized controlled trial CRC-NORDIET were included in this cross-sectional study. Corresponding abdominal volumes were acquired by Lunar iDXA and from clinically acquired CT examinations. Also, single CT slices at L2-, L3-and L4-level were obtained. Agreement between the methods was investigated using univariate linear regression and Bland-Altman plots. RESULTS: Sixty-six CRC patients were included. Abdominal volumetric VAT and FM measured by DXA explained up to 91% and 96% of the variance in VAT and FM by CT, respectively. Bland-Altman plots demonstrated an overestimation of VAT by DXA compared to CT (mean difference of 76 cm3) concurrent with an underestimation of FM (mean difference of -319 cm3). A higher overestimation of VAT (p = 0.015) and underestimation of FM (p = 0.036) were observed in obese relative to normal weight subjects. VAT in a single slice at L3-level showed the highest explained variance against CT volume (R2 = 0.97), but a combination of three slices (L2, L3, L4) explained a significantly higher variance than L3 alone (R2 = 0.98, p < 0.006). The anthropometric measurements explained between 31-65% of the variance of volumetric VAT measured by DXA and CT. CONCLUSIONS: DXA and the combined use of three CT slices (L2-L4) are valid to predict abdominal volumetric VAT and FM in CRC patients when using volumetric CT as a reference method. Due to the poor performance of anthropometric measurements we recommend exploring the added value of advanced body composition by DXA and CT integrated into CRC care.

Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer- a validation study.

BACKGROUND & AIMS: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). METHODS: A total of 136 women and men (50-80 years) with stage I-III CRC and a wide range of baseline FFM (35.7-73.5 kg) were included in the study. Body composition was measured at study baseline within 2-9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). RESULTS: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60-76%) or a gain in FFM of ≥5% (33-62%) was poor. CONCLUSION: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis.

Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals.

BACKGROUND: Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. OBJECTIVES: The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. METHODS: We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. RESULTS: Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. CONCLUSION: Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.

Plasma Biomarkers of Insulin and the Insulin-like Growth Factor Axis, and Risk of Colorectal Adenoma and Serrated Polyp.

BACKGROUND: Hyperinsulinemia, high insulin-like growth factor 1 (IGF1) levels, and low IGF binding protein 1 (IGFBP1) levels have been implicated in the relationship between obesity and increased risk of colorectal cancer (CRC). However, it remains inconclusive whether circulating biomarkers of insulin and the IGF axis are associated with conventional adenoma and serrated polyp, the two distinct groups of CRC precursors. METHODS: We prospectively examined the associations of plasma C-peptide, IGF1, IGFBP1, IGFBP3, and IGF1 to IGFBP3 ratio with conventional adenoma and serrated polyp among 11 072 women from the Nurses' Health Studies. Multivariable logistic regression was used to calculate the odds ratio (OR) per 1-SD increase in each biomarker for overall risk of conventional adenoma and serrated polyp and according to polyp feature. RESULTS: During 20 years of follow-up, we documented 1234 conventional adenomas and 914 serrated polyps. After adjusting for various lifestyle factors (including body mass index), higher concentrations of IGFBP1 were associated with lower risk of serrated polyp (OR = 0.84, 95% confidence interval = 0.75 to 0.95, P = .005). The association was particularly strong for large serrated polyp (≥10 mm) located in the distal colon and rectum (OR = 0.59, 95% confidence interval = 0.39 to 0.87, P = .01). In contrast, we did not find any statistically significant association between the biomarkers and conventional adenoma. CONCLUSIONS: A higher plasma level of IGFBP1 was associated with lower risk of serrated polyp. Our findings support a potential role of IGFBP1 in the serrated pathway of CRC in women.

Sex-Specific Association between Family History of Diabetes and Risk of Colorectal Cancer: Two Prospective Cohort Studies.

Type 2 diabetes (T2D) is associated with increased risk of colorectal cancer. It remains unclear whether family history of diabetes influences colorectal cancer risk and relevant biomarkers. We followed 101,323 women from the Nurses' Health Study (1982-2012) and 48,542 men from the Health Professionals Follow-up Study (1988-2012), free of cancer and inflammatory bowel disease at baseline. Participants reported whether any of their first-degree family members ever had diabetes in multiple questionnaires administered biennially. Plasma levels of colorectal cancer-related biomarkers were measured in subsets of participants from previous nested case-control studies. We documented 1,950 colorectal cancer cases in women and 1,173 colorectal cancer cases in men. After adjustment for potential confounders including obesity and diabetes, the hazard ratio (HR) for colorectal cancer among men who had family history of diabetes was 1.19 [95% confidence interval (CI), 1.04-1.36) as compared with those who did not. The corresponding HR was 1.06 among women (95% CI, 0.96-1.17). Interestingly, for individuals younger than 60 years, these associations appeared stronger among men (HR, 1.65; 95% CI, 1.15-2.38) and possibly among women (HR, 1.23; 95% CI, 0.99-1.54). Moreover, family history of diabetes was related to reduced levels of estradiol, sex hormone binding globulin (SHBG), and adiponectin in men, with a greater reduction of SHBG for those younger than 60 years (P for interaction = 0.03). In conclusion, family history of diabetes was associated with increased colorectal cancer risk in men, which may be partly mediated by altered sex hormones and adiponectin. The possible positive association in younger women needs further confirmation. Cancer Prev Res; 11(9); 535-44. ©2018 AACR.

Relative validity of a short food frequency questionnaire assessing adherence to the Norwegian dietary guidelines among colorectal cancer patients.

BACKGROUND: The Norwegian food-based dietary guidelines (FBDG) aim at reducing the risk of developing chronic diseases and promote overall health. We studied the effect of the Norwegian FBDG in colorectal cancer (CRC) patients. There is a need for a time-efficient dietary assessment tool measuring adherence to these guidelines in patients treated for dietary dependent cancer, such as CRC patients. OBJECTIVE: To evaluate a new short food frequency questionnaire (NORDIET-FFQ), developed to estimate adherence to the Norwegian FBDG among CRC patients. DESIGN: Eighty-one CRC patients from both study groups in the Norwegian Dietary Guidelines and Colorectal Cancer Survival study, an ongoing dietary intervention, completed both the short 63-item NORDIET-FFQ and a 7-day weighed food record. RESULTS: The NORDIET-FFQ was on group level able to estimate intakes of fruits, vegetables, unsalted nuts, fish, fatty fish, high fat dairy products, unprocessed meat, processed meat, red meat, water, sugar-rich beverages, alcoholic drinks, and sugar- and fat-rich foods. Ranking of individuals according to intake was good (r = 0.31-0.74) for fruits and vegetables, fruits, unsalted nuts, whole grain products, sugar-rich cereals, fish, fatty fish, dairy products, red meat, water, sugar-rich beverages, alcoholic beverages, and sugar- and fat-rich foods. The NORDIET-FFQ was able to identify the individuals who did not fulfil the recommendations of fruits, vegetables, unsalted nuts, whole grains, low-fat dairy products, processed meat, water, alcoholic beverages, and sugar- and fat-rich foods (sensitivity: 67-93%). CONCLUSIONS: The NORDIET-FFQ showed good ability in to estimate intakes of plant-based foods, fish, dairy products, meat, and energy-dense foods; adequate ranking of individuals according to intake of most recommendations except for unprocessed meat, processed meat, and vegetables; and importantly a good ability to identify those patients in need of dietary counselling for foods that are known to modulate the risk of CRC. TRIAL REGISTRATION: National Institutes of Health ClinicalTrials.gov; Identifier: NCT01570010.

Agreement between PG-SGA category and fat-free mass in colorectal cancer patients.

BACKGROUND AND AIMS: Low fat-free mass (FFM) is associated with adverse outcomes in colorectal cancer (CRC) patients. Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used tool developed to detect patients with malnutrition or at risk of malnutrition. The aim of this study was to investigate the agreement between PG-SGA category and FFM in patients with non-metastatic CRC. METHODS: Ninety-seven patients were included and categorized as well nourished (PG-SGA:A, n = 67) or malnourished (PG-SGA:B, n = 30). No patients were severely malnourished (PG-SGA: C). Bioelectrical impedance analysis (BIA) was used to assess FFM. Low FFM was defined as low fat-free mass index (FFMI) according to cut-off values recently proposed by The European Society for Clinical Nutrition and Metabolism (ESPEN). RESULTS: Twenty-nine percent of the patients were identified with low FFMI. The proportion with low FFMI was significantly higher among patients classified as malnourished by PG-SGA compared to well nourished (p = 0.015). The sensitivity was however low, as the PG-SGA categorization classified only 50.0% of the patients with low FFMI as malnourished (PG-SGA B). Using the PG-SGA scores (cut-off point > 4), the sensitivity increased to 60.7%. Physical examination in the PG-SGA identified only 64.3% of the patients with low FFMI as muscle depleted. CONCLUSION: Our results indicate a low agreement between PG-SGA category and low FFMI among patients with non-metastatic CRC. In clinical practice, PG-SGA should be supplemented by muscle mass assessments by BIA or other methods in order to detect low FFM in this patient group.

Validity of bioelectrical impedance analysis in estimation of fat-free mass in colorectal cancer patients.

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) is an accessible and cheap method to measure fat-free mass (FFM). However, BIA estimates are subject to uncertainty in patient populations with altered body composition and hydration. The aim of the current study was to validate a whole-body and a segmental BIA device against dual-energy X-ray absorptiometry (DXA) in colorectal cancer (CRC) patients, and to investigate the ability of different empiric equations for BIA to predict DXA FFM (FFMDXA). METHODS: Forty-three non-metastatic CRC patients (aged 50-80 years) were enrolled in this study. Whole-body and segmental BIA FFM estimates (FFMwhole-bodyBIA, FFMsegmentalBIA) were calculated using 14 empiric equations, including the equations from the manufacturers, before comparison to FFMDXA estimates. RESULTS: Strong linear relationships were observed between FFMBIA and FFMDXA estimates for all equations (R2 = 0.94-0.98 for both devices). However, there were large discrepancies in FFM estimates depending on the equations used with mean differences in the ranges -6.5-6.8 kg and -11.0-3.4 kg for whole-body and segmental BIA, respectively. For whole-body BIA, 77% of BIA derived FFM estimates were significantly different from FFMDXA, whereas for segmental BIA, 85% were significantly different. For whole-body BIA, the Schols* equation gave the highest agreement with FFMDXA with mean difference ±SD of -0.16 ± 1.94 kg (p = 0.582). The manufacturer's equation gave a small overestimation of FFM with 1.46 ± 2.16 kg (p < 0.001) with a tendency towards proportional bias (r = 0.28, p = 0.066). For segmental BIA, the Heitmann* equation gave the highest agreement with FFMDXA (0.17 ± 1.83 kg (p = 0.546)). Using the manufacturer's equation, no difference in FFM estimates was observed (-0.34 ± 2.06 kg (p = 0.292)), however, a clear proportional bias was detected (r = 0.69, p < 0.001). Both devices demonstrated acceptable ability to detect low FFM compared to DXA using the optimal equation. CONCLUSION: In a population of non-metastatic CRC patients, mostly consisting of Caucasian adults and with a wide range of body composition measures, both the whole-body BIA and segmental BIA device provide FFM estimates that are comparable to FFMDXA on a group level when the appropriate equations are applied. At the individual level (i.e. in clinical practice) BIA may be a valuable tool to identify patients with low FFM as part of a malnutrition diagnosis.

DNA damage in blood cells in relation to chemotherapy and nutritional status in colorectal cancer patients-A pilot study.

DNA damage can be considered as a biomarker for toxicity and response to chemotherapy. It is not known whether the chemotherapy-induced genotoxicity is associated with malnutrition. In this pilot study, we assess genotoxicity by means of DNA damage in patients with lymph-node positive colorectal cancer (CRC) and explore associations with chemotherapy treatment and nutritional status. DNA damage was compared between patients receiving chemotherapy (n = 24) and those not receiving chemotherapy (n = 20). DNA damage was measured in frozen whole blood by the comet assay. Associations between DNA damage and various indicators of malnutrition were also explored, including Patient-Generated Subjective Global Assessment (PG-SGA), bioelectrical impedance analysis (BIA) and anthropometric measurements, using multiple linear regression models. Patients on chemotherapy have higher levels of DNA damage in blood cells than patients not receiving chemotherapy (median of 16.9 and 7.9% tail DNA respectively, p = 0.001). The moderately malnourished patients (PG-SGA category B), representing 41% of the patients, have higher levels of cellular DNA damage than patients with good nutritional status (mean difference of 7.5% tail DNA, p = 0.033). In conclusion, adjuvant chemotherapy and malnutrition are both associated with increased levels of DNA damage in blood cells of CRC patients. Carefully controlled longitudinal studies or randomized controlled trials should be performed to determine whether good nutritional status may protect against chemotherapy-induced genotoxicity and enhance compliance to therapy in CRC patients.