Lower Risk Of Colorectal Cancer Research Articles

Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations.

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini–Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

Intentional Weight Loss and Obesity-Related Cancer Risk.

BackgroundEpidemiologic studies regarding weight loss and subsequent cancer risk are sparse. The study aim was to evaluate the association between weight change by intentionality and obesity-related cancer incidence in the Women’s Health Initiative Observational Study. Eleven cancers were considered obesity related: breast, ovary, endometrium, colon and rectum, esophagus, kidney, liver, multiple myeloma, pancreas, stomach, and thyroid.MethodsPostmenopausal women (n = 58 667) aged 50–79 years had body weight and waist circumference (WC) measured at baseline and year 3. Weight or WC change was categorized as stable (change < ±5%), loss (≥5%), and gain (≥5%). Self-report at year 3 characterized weight loss as intentional or unintentional. During the subsequent 12 years (mean) of follow-up, 6033 incident obesity-related cancers were identified. Relationships were evaluated using multivariable Cox proportional hazards regression models.ResultsCompared to women with stable weight, women with intentional weight loss had lower obesity-related cancer risk (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.80 to 0.98). A similar result was observed for intentional WC reduction (HR = 0.88, 95% CI = 0.80 to 0.96). Among all cancers, intentional weight loss was most strongly associated with endometrial cancer (HR = 0.61, 95% CI = 0.42 to 0.88). Intentional WC loss was also associated with lower colorectal cancer risk (HR = 0.79, 95% CI = 0.63 to 0.99). Unintentional weight loss or weight gain was not associated with overall obesity-related cancer risk.ConclusionIntentional weight or WC loss in postmenopausal women was associated with lower risk of obesity-related cancer. These findings suggest that postmenopausal women who intentionally lose weight can reduce their obesity-related cancer risk.

Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans

Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20-45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1-V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography-mass spectrometry. We detected 32 DE genes (false discovery rate <0.05) in the exfoliome, but none in the mucosal biopsies, in response to 60 d of lignan supplement compared with placebo. Statistically significant associations were detected between ENL excretion and fecal microbiome measured at baseline and at the end of the intervention periods. Further, we detected DE genes in colonic mucosa and exfoliome between low- and high-ENL excreters. Analysis of biopsy samples indicated that several anti-inflammatory upstream regulators, including transforming growth factor β and interleukin 10 receptor, were suppressed in low-ENL excreters. Complementary analyses in exfoliated cells also suggested that low-ENL excreters may be predisposed to proinflammatory cellular events due to upregulation of nuclear transcription factor κB and NOS2, and an inhibition of the peroxisome proliferator-activated receptor γ network. These results suggest that ENL or other activities of the associated gut microbial consortia may modulate response to a dietary lignan intervention. This has important implications for dietary recommendations and chemoprevention strategies. This study was registered at clinicaltrials.gov as NCT01619020.

Abstract 629: Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort

Abstract Coffee consumption is inconsistently associated with colorectal cancer (CRC) risk, and further research on potential differences in associations by sex, colorectal subsite, smoking status, and caffeinated/decaffeinated coffee is needed. To investigate associations of coffee consumption with risk of CRC, we analyzed data from the Cancer Prevention Study-II Nutrition prospective cohort study. This analysis included 46,970 men and 60,007 women without a history of cancer at baseline. Those who completed a semiquantitative food frequency questionnaire in 1999 were followed through 2013, and 1,706 verified incident CRC cases were identified. Daily servings of caffeinated and decaffeinated coffee were comparable between men and women. Of the total population, 4.6% were current smokers, 46.1% were never smokers, and 47.3% were former smokers (2% missing smoking status). Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of coffee consumption with CRC risk, adjusted for age, sex, body mass index, smoking, alcohol intake, total energy, total calcium (energy-adjusted), red and processed meat, and decaffeinated coffee in caffeinated coffee models and vice versa. For those who consumed 2 or more cups per day relative to those who consumed none or less than 1 cup per month, caffeinated coffee was not associated with CRC risk (HR 1.06, 95% CI 0.93-1.20), but decaffeinated coffee was associated with 15% lower risk of CRC (HR 0.85, 95% CI 0.73-0.99). Current smokers tend to consume more coffee in our study population and in other studies, and smoking is an established risk factor for some molecular sub-types of CRC; therefore, we repeated analyses stratified by smoking status (controlling for smoking duration for non-smokers and dose for current smokers). Among non-smokers (includes never and former smokers), the associations for coffee and CRC risk were similar to the overall results (HR 1.03, 95% CI 0.90-1.18 for caffeinated coffee; HR 0.87, 95% CI 0.74-1.02 for decaffeinated coffee). Among current smokers, the adjusted HRs and 95% CIs were 1.60 (0.80-3.22) for caffeinated coffee and 0.45 (0.19-1.03) for decaffeinated coffee. There was no evidence of effect modification by sex or colorectal subsite. Our results suggest that decaffeinated coffee may be associated with lower risk of CRC, but do not suggest potential differences in risk between men and women or by colorectal subsites. Further studies are needed to confirm these findings and to explore potential differences in caffeinated and decaffeinated coffee. Citation Format: Caroline Y. Um, Marjorie L. McCullough, Mark A. Guinter, Peter T. Campbell, Eric J. Jacobs, Susan M. Gapstur. Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 629.

Eat Your Yogurt

Yogurt consumption has been associated with lower colorectal cancer (CRC) risk, but its relation to polyp risk is unknown. To investigate this issue,

Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA wasassociated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Association between grains, gluten and the risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.

Evidence supports a role of whole grains in colorectal cancer (CRC) prevention, but the association between gluten intake and CRC risk in healthy populations is unclear. We examined the association of grain and gluten intake with risk of CRC overall and by subsite among Cancer Prevention Study-II Nutrition Cohort participants. In 1999, 50,118 men and 62,031 women completed food frequency questionnaires assessing grain intake. Gluten intake was estimated using the protein content of grain products. Multivariable-adjusted hazards ratio (HR) and 95% confidence interval (CI) of CRC risk were estimated using Cox proportional hazards regression. During follow-up through 2013, 1742 verified CRC cases occurred. For the highest vs. lowest quintiles of whole grain intake, HRs (95% CIs) of CRC risk were 0.77 (0.61-0.97; P trend = 0.03) among men and 1.10 (95% CI 0.88-1.36; P trend = 0.14) among women (P interaction by sex = 0.01). Men in the highest vs. lowest quintile of whole grain intake had a 43% lower risk of rectal cancer (HR = 0.57, 95% CI 0.35-0.93, P trend = 0.04). Gluten intake was not associated with CRC risk overall (HR = 1.10, 95% CI 0.93-1.32, P trend = 0.10), but was associated with risk of proximal colon cancer among men and women, combined (HR = 1.37, 95% CI 1.07-1.75, quintile 5 vs. 1, P trend = 0.001) and separately. Refined grains and grain-based sweets were not associated with CRC risk. We found that higher whole grain intake was associated with lower CRC risk among older US men, but not women. The positive association of gluten intake with the risk of proximal colon cancer deserves further study.

Physical activity during adolescence and risk of colorectal adenoma later in life: results from the Nurses\u2019 Health Study II

BackgroundPhysical activity during adulthood has been consistently associated with lower risk of colorectal cancers, but whether physical activity during adolescence may also play a role in colorectal carcinogenesis is unclear.MethodsWe included 28,250 women in the Nurses’ Health Study II who provided data on physical activity during adolescence (ages 12–22 years) in 1997 and underwent lower bowel endoscopy (1998–2011). We used logistic regression models for clustered data to examine the association between physical activity during adolescence and risk of adenoma later in life.ResultsPhysical activity during adolescence was inversely associated with risk of colorectal adenoma (2373 cases), independent of physical activity during adulthood. The multivariable-adjusted odds ratio (OR) of adenoma was 0.89 (95% CI 0.77–1.02; Ptrend = 0.03) comparing women with ≥ 72 metabolic equivalent of tasks-hours/week (MET-h/week) to < 21 MET-h/week. Women with high physical activity during both adolescence (≥53.3 MET-h/week) and adulthood (≥23.1 MET-h/week) had significantly lower risk of adenoma (all adenomas: OR 0.76; 95% CI 0.66–0.88; advanced adenoma: OR 0.61; 95% CI 0.45–0.82) compared to women with low physical activity during both stages of life.ConclusionsOur findings suggest that physical activity during adolescence may lower the risk of colorectal adenoma later in life.

Dietary intake of fiber, whole grains and risk of colorectal cancer: An updated analysis according to food sources, tumor location and molecular subtypes in two large US cohorts.

Epidemiologic evidence relating fiber intake to colorectal cancer (CRC) remains inconclusive and data are limited on different food sources of fiber and heterogeneity by tumor subsite and molecular profile. We prospectively followed for CRC incidence 90,869 women from the Nurses' Health Study (1980-2012) and 47,924 men from the Health Professionals Follow-up Study (1986-2012), who completed a validated food frequency questionnaire every 4 years. Cox proportional hazards regression was used to examine the associations with CRC risk for total, cereal, fruit and vegetable fiber and whole grains. We also assessed the associations according to tumor subsites (proximal colon, distal colon and rectum) and molecular markers (microsatellite instability, BRAF mutation, CpG island methylator phenotype and KRAS mutation). We documented 3,178 CRC cases during 3,685,903 person-years of follow-up in the NHS and HPFS. Intake of total dietary fiber was not associated with CRC risk after multivariable adjustment in either women (hazard ratio [HR] comparing extreme deciles, 1.17; 95% CI, 0.92-1.48, ptrend = 0.55) or men (HR, 0.90; 95% CI, 0.67-1.21, ptrend = 0.47). Higher intake of cereal fiber and whole grains was associated with lower CRC risk in men with an HR of 0.75 (95% CI, 0.57-1.00) and 0.72 (95% CI, 0.54-0.96), respectively. No heterogeneity was detected by tumor subsite or molecular markers (pheterogeneity > 0.05). Higher intake of total dietary fiber within the range of a typical American diet is unlikely to substantially reduce CRC risk. The potential benefit of cereal fiber and whole grains in men warrants further confirmation.

Use of Phosphodiesterase 5 Inhibitors Is Associated With Lower Risk of Colorectal Cancer in Men With Benign Colorectal Neoplasms

Phosphodiesterase 5 (PDE5) inhibitors have been proposed to have chemopreventative effects on colorectal cancer (CRC), although data are needed from population-based studies. We performed a nationwide cohort study to investigate the association between the use of PDE5 inhibitors and the risk of CRC in men with benign colorectal neoplasms. We identified men who received a diagnosis of benign colorectal neoplasm from July 2005 through March 2015 who were listed in the Swedish Hospital Discharge Register. We linked data with those from other national Swedish registers to obtain information about the prescription of PDE5 inhibitors and CRC diagnoses. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 4823 patients were prescribed PDE5 inhibitors during the study period; the incidence rate of CRC was 2.64 per 1000 person-years for men prescribed PDE5 inhibitors compared with 4.46 per 1000 person-years for men without a prescription. We found a significant negative association between PDE5 inhibitor use and risk of CRC (adjusted HR, 0.65; 95% CI, 0.49-0.85); the decreased risk of CRC was associated with an increased cumulative dose of PDE5 inhibitors (P= .003). PDE5 prescription was associated with greater reduction in risk of advanced-stage CRC (adjusted HR, 0.61; 95% CI, 0.37-1.00) than early-stage CRC (adjusted HR, 0.70; 95% CI, 0.50-0.98), but the difference was not significant. In a nationwide population-based study of men with a diagnosis of benign colorectal neoplasm in Sweden, we found evidence that use of PDE5 inhibitors is associated with a reduced risk of CRC. Further studies are needed to confirm the observed association.

Association Between Dairy Product Consumption and Colorectal Cancer Risk in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Studies

Dairy product consumption may decrease colorectal cancer (CRC) risk, but very few studies have evaluated the association between different types of dairy products and CRC location. The aim of this systematic review and meta-analysis was to examine the associations between dairy product consumption and CRC incidence. Summary RRs and ORs with 95% CIs were estimated. A total of 15 cohort studies and 14 case-control studies comprising a total of >22,000 cases were included in the quantitative synthesis. The cohort studies showed a consistent significant decrease in CRC risk associated with higher consumption of total dairy products (RR:0.80; 95% CI: 0.70, 0.91) and total milk (RR: 0.82; 95% CI: 0.76, 0.88) compared with the CRC risk associated with lower consumption. These studies also showed a significant protective association between low-fat milk consumption and CRC (RR: 0.76; 95% CI: 0.66, 0.88), but only for colon cancer (RR: 0.73; 95% CI: 0.61, 0.87). Cheese consumption was inversely associated with the risk of CRC (RR: 0.85; 95% CI: 0.76, 0.96) and proximal colon cancer (RR: 0.74; 95% CI: 0.60, 0.91). No significant associations with CRC were found for the consumption of low-fat dairy products, whole milk, fermented dairy products, or cultured milk. Most of these associations were not supported by the case-control studies. In conclusion, high consumption of total dairy products and total milk was associated with a lower risk of developing CRC at any anatomic location, including the proximal and distal colon and the rectum. Low-fat milk consumption was associated with a lower risk of CRC, but this association was restricted to colon cancer. Cheese consumption was associated with the prevention of CRC, specifically proximal colon cancer. Further studies on larger samples and with longer follow-up periods, along with appropriately designed and executed clinical trials, are warranted to determine whether dairy product consumption affects CRC development.

Physical Activity and Colorectal Cancer Risk by Sex, Race/Ethnicity, and Subsite: The Multiethnic Cohort Study.

Physical activity has been associated with a lower risk of colorectal cancer. However, data is lacking on whether the association is consistent between sexes and across different races/ethnicities and anatomic subsites of tumors. We analyzed data from the Multiethnic Cohort in Hawaii and California, consisting of mostly African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites ages 45-75 years at recruitment. During a mean follow-up of 16.8 years, 4,430 invasive adenocarcinoma cases of the colorectum were identified among 172,502 eligible participants. Cox proportional hazards models were used to estimate the HR and 95% confidence interval (CI). The multivariate-adjusted HR (95% CI) for the highest versus lowest quintiles of physical activity (metabolic equivalent hours of moderate or vigorous activities per day) was 0.76 (0.66-0.87) in men (P trend < 0.001) and 0.94 (0.80-1.11) in women (P trend = 0.53, P heterogeneity by sex = 0.07). Sleeping and sitting hours were not associated with colorectal cancer risk both in men and women. In men, the inverse association was statistically significant among African Americans and Japanese Americans, for right colon and rectal cancer, and in all body mass index groups, although heterogeneity tests were not significant across race/ethnicity or anatomic subsite of tumors. The findings confirm the inverse association between physical activity and colorectal cancer, which appears to be stronger in men, and suggest possible differences in the strength of the association by race/ethnicity and anatomic subsite of tumors.

Highlights of This Issue

Urban–rural disparities in treatment are often attributed to the longer distances rural patients must travel to receive care. However, recent evidence suggests that distance to care has a differential effect on urban and rural patients. Spees and colleagues examined the influence of distance on the timely treatment initiation and completion in women with cervical cancer. In urban areas, living further away from care was associated with a lower likelihood of initiating treatment. However, rural women with advanced cervical cancer residing farther from care were more likely to complete timely treatment. Distance was not associated with timely treatment completion among urban women. Distance is an access barrier for cervical cancer patients in urban areas whereas rural patients may require more intensive support, even among those living closer to treatment.The role of vitamin D in cancer risk is contentious and data on associations with tumor subtypes are limited. Heath and colleagues investigated the association between prediagnostic 25-hydroxyvitamin D (25(OH)D) concentration and risk of incident colorectal, breast, and prostate cancers and subtypes of these cancers in a cohort of middle-aged Australians. Circulating 25(OH)D was not associated with risk of breast cancer or prostate cancer, whereas higher 25(OH)D was associated with a lower risk of colorectal cancer in women and BRAF V600E-mutant colorectal cancer. Vitamin D might be important for preventing some colorectal cancer in women and specifically BRAF-mutant tumors.Ascha and colleagues describe incidence proportions (IP) of both synchronous (SBM) and lifetime brain metastases (LBM) for primary lung, breast, and skin cancers, validating their Medicare-derived estimates of lifetime incidence by comparison with cancer registry data. The SBM IP was highest in lung (specifically for non–small cell lung cancer) followed by breast and melanoma cancers; the LBM IP was also highest in lung (specifically for small-cell lung cancer), followed by breast and melanoma cancers. Large population-based datasets such as SEER-Medicare allow for accurate estimates of both SBM and LBM for an elderly U.S. population.Palazzo and colleagues analyzed cancer registry data to identify patient factors associated with the utilization of genetic testing and treatment with erlotinib, a targeted therapy drug for metastatic non–small cell lung cancer, and to examine how these associations changed over time. Patient age was found to be associated with genetic testing; race, gender, and income level were associated with erlotinib treatment. Some of these disparities decreased in magnitude over time, while others remained stable or grew. This study highlights the need to reduce disparities as precision cancer treatments continue to be developed.

Calcium Intake and Risk of Colorectal Cancer According to Tumor-infiltrating T Cells.

Calcium intake has been associated with a lower risk of colorectal cancer. Calcium signaling may enhance T-cell proliferation and differentiation, and contribute to T-cell-mediated antitumor immunity. In this prospective cohort study, we investigated the association between calcium intake and colorectal cancer risk according to tumor immunity status to provide additional insights into the role of calcium in colorectal carcinogenesis. The densities of tumor-infiltrating T-cell subsets [CD3+, CD8+ , CD45RO (PTPRC) + , or FOXP3+ cell] were assessed using IHC and computer-assisted image analysis in 736 cancer cases that developed among 136,249 individuals in two cohorts. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Total calcium intake was associated with a multivariable HR of 0.55 (comparing ≥1,200 vs. <600 mg/day; 95% CI, 0.36-0.84; P trend = 0.002) for CD8+ T-cell-low but not for CD8+ T-cell-high tumors (HR = 1.02; 95% CI, 0.67-1.55; P trend = 0.47). Similarly, the corresponding HRs (95% CIs) for calcium for low versus high T-cell-infiltrated tumors were 0.63 (0.42-0.94; P trend = 0.01) and 0.89 (0.58-1.35; P trend = 0.20) for CD3+ ; 0.58 (0.39-0.87; P trend = 0.006) and 1.04 (0.69-1.58; P trend = 0.54) for CD45RO+ ; and 0.56 (0.36-0.85; P trend = 0.006) and 1.10 (0.72-1.67; P trend = 0.47) for FOXP3+ , although the differences by subtypes defined by T-cell density were not statistically significant. These potential differential associations generally appeared consistent regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status. Our findings suggest a possible role of calcium in cancer immunoprevention via modulation of T-cell function.

Genome-wide expression profiling-based copy number variations and colorectal cancer risk in Chinese.

Genetic factors play important roles in colorectal carcinogenesis. This study was aimed to evaluate the effects of gene expression-related copy number variations (CNVs) on the risk of colorectal cancer in Chinese. Expression Quantitative Trait Locus (eQTL) mapping was conducted to explore the most regulatable gene expressions by CNVs among the whole genome based on publicly available data. Then a case-control study was performed to evaluate the associations between copy numbers of the most regulatable genes and colorectal cancer. The influence of the target CNVs on the expression of corresponding gene and protein was verified in colorectal tissue, and the biological effects of these CNVs on cell-cycle arrest and apoptosis of colon cancer cell lines were further detected. The eQTL revealed the most significant association between CNV of HM3_CNP_342 and gene expressions of human leukocyte antigen (HLA)-DQA1 and HLA-DQB1 among the whole genome. The later case-control study found that amplified HLA-DQB1 was inversely associated with colorectal cancer risk (odds ratio = 0.73; 95% confidence interval: 0.58-0.93), especially among those with a family history of cancer. The positive association between amplified HLA-DQB1 and upregulation of gene and protein was validated in colorectal tissue. In addition, overexpression of HLA-DQB1 in dendritic cells promoted cell-cycle arrest and apoptosis of cocultured SW480 and HCT116 cell lines, and vice versa. Our study suggests that the amplified copy number of HLA-DQB1 is associated with lower risk of colorectal cancer and able to induce the apoptosis of colon cancer cells, which implies the potential of HLA class II in cancer predisposition and immunotherapy.

Diet and colorectal cancer in UK Biobank: a prospective study.

BackgroundMost of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s.MethodsWe used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40–69 years at recruitment (2006–10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time.ResultsDuring an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% [95% confidence interval (CI): 4–37] higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% (95% CI: 2–24) lower risk of colorectal cancer. Alcohol was associated with an 8% (95% CI: 4–12) higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk.ConclusionsConsumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (≤90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk.

Colorectal Cancer Screening and Surveillance Colonoscopy in Older Adults.

The purpose of this chapter is to highlight current recommendations regarding colorectal cancer (CRC) screening and post-polypectomy surveillance colonoscopy in older adults and to review the available literature in order to help inform decision-making in this age group. Age is a risk factor for CRC; however, older adults with a history of prior screening are at lower risk for CRC compared to those who have never been screened. Decision-making for CRC screening and post-polypectomy surveillance colonoscopy in older adults is complex and several factors including age, screening history, comorbidities, functional status, bowel preparation, prior experiences, preferences, and barriers need to be considered when weighing risks and benefits. Recent guidelines have started to incorporate life expectancy and prior screening history into their recommendations; however, how to incorporate these factors into actual clinical practice is less clear. There are limited data on the relative benefits of screening and surveillance in older adults and therefore, at this time, decision-making should be individualized and incorporate patient preferences in addition to medical factors.

Consumption of modern and traditional Moroccan dairy products and colorectal cancer risk: a large case control study.

The main objective of this study is to describe the association between the consumption of either traditional or modern dairy products or calcium intakes and the risk of colorectal cancer (CRC) in the adult Moroccan population. A case-control study was conducted in five Moroccan hospital centers. The study was matched on sex, age (± 5years) and center. Data were collected using validated food frequency questionnaire (FFQ) taking into account different types of Moroccan dairy products. Conditional logistic regression models were used to assess the association between dairy products consumption, calcium intakes and CRC risk subtypes. In all statistical tests, the significance level was set at 0.05. Among 1453 cases and 1453 matched controls, 50.7% were women and 49.3% were men. Milk ORb 0.84, 95% CI 0.74-0.96 and yogurt ORb 0.74, 95% CI 0.64-0.86 were inversely associated with CRC risk. Similar inverse associations were observed for traditional dairy products namely Lben ORb 0.77, 95% CI 0.67-0.88, Raib ORb 0.86, 95% CI 0.76-0.96 and Jben ORb 0.77, 95% CI 0.67-0.88. The dairy calcium intake was inversely associated to CRC overall ORb 0.83, 95% CI 0.74-0.93. Our study supports previous international evidence and suggests that individuals who have a high intake of either modern or traditional dairy products are at lower risk for CRC. These findings should be further confirmed by longitudinal data and studies investigating potential pathways involved.

Concordance with the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention and colorectal cancer risk in Morocco: A large, population-based case-control study.

The present study aimed to investigate associations between adherence to the recommendations on cancer prevention from the WCRF/AICR and colorectal cancer (CRC) risk in Morocco. Incident CRC cases (n = 1,516) and controls (n = 1,516) matched on age, sex and center, were recruited between September 2009 and February 2017 at five major hospitals located in Morocco. In-person interviews were conducted to assess habitual diet using a validated Food Frequency Questionnaire, physical activity and anthropometric measurements. Adherence to the WCRF/AIRC Recommendations was ranged from 0 (no adherence) to 6 (maximal adherence) and incorporating six WCRF/AICR components (food groups, physical activity and BMI). Multivariable odd ratios (ORA ) and 95% confidence intervals (CI) were calculated using conditional multivariate logistic regression models, with low adherence as referent, adjusting for potential confounding factors. Compared to those with the lowest adherence score, individuals in the highest WCRF/AICR score category had a statistically significant reduced risk for colon cancer (ORA = 0.63, 95% CI 0.53-0.76); rectal cancer (ORA = 0.52, 95% CI 0.43-0.63) and CRC overall (ORA = 0.58, 95% CI 0.51-0.66). For individual score components, when comparing the lowest with the highest adherence category, CRC risk was significantly lower in the highest adherence category for body fatness (ORA = 0.73; 95% CI 0.62-0.85), physical activity (ORA = 0.70; 95% CI 0.60-0.82), plant foods (ORA = 0.50; 95% CI 0.39-0.63) and red/processed meat (ORA = 0.81; 95% CI 0.71-0.92). Our analysis indicated that greater adherence to the WCRF/AICR recommendations for cancer prevention may lower CRC risk in Morocco.

Diet and colon: what matters?

Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer-related deaths worldwide. Diet has a significant impact on the risk of developing CRC, but though processed meat is a known positive contributor, the effects of other dietary components are largely mixed. This review focuses on dietary patterns to describe the complexity of dietary diversity and overall food consumption and to examine the relationship between dietary patterns and risk of CRC. After searching human studies published in 2017-2018, we selected and evaluated 30 articles, including meta-analyses, cohort studies, and prospective studies. These studies suggest that the prudent or Mediterranean dietary pattern significantly decreases the risk of CRC compared to the Western dietary pattern; a lower dietary inflammatory index or a higher dietary quality index associates with a lower risk of CRC; closely following all aspects of the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines and recommendations correlates with a reduced risk of CRC. The risk of developing CRC can be reduced by adopting a healthier lifestyle. More studies of the impact of diet on clinical outcomes of CRC are needed.