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Dietary factors account for a large proportion of human cancers, particularly overnutrition that results in weight gain and obesity. The evidence linking diet and cancer has been developing since the early 1900s, beginning with early laboratory studies and ecologic studies of cancer rates in different parts of the world. More modern epidemiologic methods, including case–control studies, cohort studies, and randomized controlled trials have helped define in detail the associations between specific dietary factors and cancer. Factors with strong links to an increased risk of various cancers include: overnutrition/obesity, alcohol, red meat, and salt. Factors with strong links to a decreased risk include: fruits, vegetables, fiber, vitamin D, calcium, and folate.

Purpose Cancer of unknown primary (CUP) is a metastasised cancer for which no primary lesion could be identified during life. Research into CUP aetiology with respect to dietary factors is particularly scarce. This study investigates whether meat consumption is associated with CUP risk. Methods Data was utilised from the prospective Netherlands cohort study that includes 1,20,852 participants aged 55–69 years. All participants completed a self-administered questionnaire on diet and other cancer risk factors at baseline. Cancer follow-up was established through record linkage to the Netherlands Cancer Registry and the Dutch Pathology Registry. A total of 899 CUP cases and 4111 subcohort members with complete and consistent dietary data were available for case–cohort analyses after 20.3 years of follow-up. Multivariable adjusted hazard ratios (HRs) were calculated using proportional hazards models. Results We found a statistically significant positive association with beef and processed meat consumption and CUP risk in women (multivariable adjusted HR Q4 vs. Q1 1.47, 95% CI 1.04–2.07, Ptrend = 0.004 and Q4 vs. Q1 1.53, 95% CI 1.08–2.16, Ptrend = 0.001, respectively), and a non-significant positive association with processed meat consumption and CUP risk in men (multivariable adjusted HR Q4 vs. Q1 1.33, 95% CI 0.99–1.79, Ptrend = 0.15). No associations were observed between red meat (overall), poultry or fish consumption and CUP risk. Conclusion In this cohort, beef and processed meat consumption were positively associated with increased CUP risk in women, whereas a non-significant positive association was observed between processed meat consumption and CUP risk in men.

Atrial fibrillation (AF) is considered the most common sustained arrhythmia. Major cardiovascular risk factors that have been identified to initiate and perpetuate AF include age, sex, arterial hypertension, heart failure, valvular heart disease and diabetes mellitus. In the literature, several studies aimed to formulate easily – applied and accurate risk stratification scores, based on antecedent cardiovascular events, comorbidities and biomarkers for the prediction of new-onset AF. The present narrative review addresses the most universally accepted and efficient clinical scores, with an extended applicability in different populations and ages, particularly scores derived from the Framingham Heart Study, the Atherosclerosis Risk in Communities, the Malmo Diet and Cancer Study, as well as the CHARGE-AF, the CHADS2, CHA2DS2-VASc, HATCH and CH2EST scores. Identification of incident AF can be challenging, thus dictating for utilization of validated clinical instruments in everyday clinical practice.

Background Prospective evidence on associations between diet quality indices and lung cancer risk is limited, particularly among older women. Objectives We investigated associations between 4 diet quality indices [Healthy Eating Index-2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)] and lung cancer incidence and mortality in the Women's Health Initiative Observational Study. Methods Postmenopausal women aged 50-79 y at baseline (1993-1998) self reported their diet intake and information on relevant covariates. We used Cox proportional hazards regression models to estimate HRs and 95% CIs after controlling for age, smoking, and other relevant covariates. Results During ∼17 y of follow-up among 86,090 participants, 1491 lung cancer cases and 1393 lung cancer deaths were documented. Dietary indices were not associated with overall lung cancer incidence but were protective against squamous cell carcinoma (12.8% of total lung cancer) cases (HEI-2015: HR: 0.85; 95% CI: 0.76, 0.96; AHEI-2010: HR: 0.87; 95% CI: 0.78, 0.98; aMED: HR: 0.90; 95% CI: 0.81, 0.99; DASH: HR: 0.87; 95% CI: 0.77, 0.98). Among the indices, only HEI-2015 showed an inverse trend (P-trend = 0.02) with overall lung cancer mortality. Smoking status or participant age at baseline did not modify the association between dietary indices and lung cancer incidence or mortality. Conclusions After comprehensive control of smoking exposure, we found that diet quality was not associated with overall lung cancer among postmenopausal women. However, a high-quality diet was inversely related to incident lung cancer of the squamous cell subtype. Future studies in populations with diverse age, smoking history, and dietary intake may further elucidate the relation between diet quality indices and lung cancer, especially by histological subtype.

Breast cancer prevention is of great importance to reduce high incidence in South Africa. This study aimed to investigate adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations and the association with breast cancer risk in black urban women from Soweto, South Africa. A total of 396 breast cancer cases and 396 population-based controls from the South African Breast Cancer study (SABC) matched on age and demographic settings were included. Validated questionnaires were used to collect dietary and epidemiological data. To assess adherence to these recommendations, an eight-point adherence score was developed, using tertiles among controls for scoring each recommendation (0, 0·5 and 1) with zero indicating the lowest adherence to the recommendations. OR and 95 % CI were estimated using multivariate logistic regression models to analyse associations between the WCRF/AICR score and breast cancer risk. Greater adherence (>4·5 v.

Purpose Selenium has been suggested to be protective against breast cancer, but the evidence remains inconclusive. Hence, it is important to further examine the potential protective effect. This prospective cohort study investigates pre-diagnostic selenium intake in relation to breast cancer risk. In addition, we analyze serum selenium as a marker of dietary intake. Methods This study includes 17,035 women in the Malmö Diet and Cancer cohort. Dietary assessment and serum samples were collected at baseline (1991–1996). During 344,584 person-years of follow-up, 1,427 incident cases were retrieved. Cox regression analysis examined breast cancer risks adjusted for potential confounding factors. In addition, odds ratios (ORs) were estimated for 1186 cases and an equal number of controls in relation to quartiles (Q) of selenium intake and groups consisting of a combination of intake and serum selenium levels. Results No overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk was found. The adjusted relative risk for breast cancer in selenium intake Q4 versus Q1 was 0.96 (0.83–1.12) (Ptrend = 0.65). Similarly, adjusted the OR for breast cancer in selenium intake for Q4 versus Q1 was 0.97 (0.76–1.23). The kappa value, 0.096 (p = 0.001), showed poor agreement between serum selenium and selenium intake. Conclusion Our findings suggest that there is no overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk. Finally, our results showed a poor correlation between estimated selenium intake and serum selenium.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selective killing of cancer cells underlines its anticancer potential. However, poor tolerability and resistance underscores the need to identify cancer-selective TRAIL-sensitizing agents. Apigenin, a dietary flavonoid, sensitizes lung cancer cell lines to TRAIL. It remains unknown, however, whether apigenin sensitizes primary lung cancer cells to TRAIL and its underlying mechanisms. Here we show that apigenin reprograms alternative splicing of key TRAIL/death-inducing-signaling-complex (DISC) components: TRAIL Death Receptor 5 (DR5) and cellular-FLICE-inhibitory-protein (c-FLIP) by interacting with the RNA-binding proteins hnRNPA2 and MSI2, resulting in increased DR5 and decreased c-FLIPS protein levels, enhancing TRAIL-induced apoptosis of primary lung cancer cells. In addition, apigenin directly bound heat shock protein 70 (Hsp70), promoting TRAIL/DISC assembly and triggering apoptosis. Our findings reveal that apigenin directs alternative splicing and inhibits Hsp70 enhancing TRAIL anticancer activity. These findings underscore impactful synergies between diet and cancer treatments opening new avenues for improved cancer treatments.

Background Prospective cohort studies on diet and cancer report risk associations as hazard ratios. But hazard ratios do not inform on the number of people who need to alter their dietary behaviours for preventing cancer. The objective of this study is to estimate the number of people that need to alter their diet for preventing one additional case of female breast or colorectal cancer. Methods Based on the largest prospective studies done in the USA and in Europe, we computed the number of subjects who need to alter their diet. Results For preventing one case of breast cancer, European women should increase their fruit consumption by 100 g/day during 33 000 person-years, and US women by 60 g/day during 10 600 person-years. For vegetables, European women should increase their consumption by 160 g/day during 26 900 person-years and US women by 100 g/day during 19 000 person-years. For preventing one case of colorectal cancer, European subjects should decrease their red meat consumption by 20 g/day during 26 100 person-years, and US subjects by 30 g/day during 8170 person-years. For processed meat, European subjects should decrease their consumption by 20 g/day during 17 400 person-years, and US subjects by 10 g/day during 7940 person-years. Conclusions Large number of subjects would need to alter their intake of fruits, vegetables, red and processed meat during many years in order to prevent one additional breast or colorectal cancer.

Background The considerable differences in food consumption across countries pose major challenges to the research on diet and cancer, due to the difficulty to generalise and reproduce the dietary patterns identified in a specific population. Methods We analysed data from a multicentric case-control study on oesophageal squamous cell carcinoma (ESCC) carried out between 1992 and 2009 in three Italian areas and in the Canton of Vaud, Switzerland, which included 505 cases and 1259 hospital controls. Dietary patterns were derived applying LCA on 24 food groups, controlling for country membership, and non-alcoholic energy intake. A multiple logistic regression model was used to derive odds ratio (ORs) and corresponding 95% CIs for ESCC according to the dietary patterns identified, correcting for classification error. Results and Conclusion We identified three dietary patterns. The ‘Prudent’ pattern was distinguished by a diet rich in fruits and vegetables. The ‘Western’ pattern was characterised by low consumption of these food groups and higher intakes of sugar. The ‘Lower consumers-combination pattern’ exhibited a diet poor in most of the nutrients, preferences for fish, potatoes, meat and a few specific types of vegetables. Differences between Italy and Switzerland emerged for pattern sizes and for specific single food preferences. Compared to the ‘Prudent’ pattern, the ‘Western’ and the ‘Lower consumers-combination’ patterns were associated with an increased risk of ESCC (OR=3.04, 95% CI=2.12–4.38 and OR=2.81, 95% CI=1.65–4.76).

At present, mostly case‐control and retrospective studies have investigated the association between etiologic risk factors and the development of histologic subtypes of renal cell carcinoma (RCC). Therefore, we assessed the heterogeneity between body mass index (BMI), cigarette smoking, alcohol consumption and hypertension across clear‐cell RCC (ccRCC) and papillary RCC (pRCC) risk in the prospective Netherlands Cohort Study on diet and cancer. In 1986, 120 852 participants aged 55 to 69 completed a self‐administered questionnaire on diet and other risk factors for cancer. Participants were followed up for cancer through record linkage. Tumor histology was assessed through centralized revision by two experienced uropathologists. After 20.3 years of follow‐up, 384 histologically verified RCC cases, including 315 ccRCC and 46 pRCC cases and 4144 subcohort members were eligible for case‐cohort analysis. Hazard ratios and 95% confidence intervals were estimated by multivariable‐adjusted proportional hazards models. Overall, BMI was associated positively with ccRCC risk, but inversely with pRCC risk. Cigarette smoking was associated with an increased ccRCC, but a decreased pRCC risk. Alcohol consumption was inversely associated with both ccRCC and pRCC risk. Hypertension was associated with an increased risk of both ccRCC and pRCC. Statistically significant etiologic heterogeneity was observed for BMI, BMI change since age 20, and smoking duration in current smokers across ccRCC and pRCC risk. In conclusion, we observed potential heterogeneity for BMI, BMI change and smoking duration across ccRCC and pRCC risk., What's new? Etiologic risk factors for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) include alcohol consumption, body mass index (BMI), cigarette smoking, and hypertension. Little is known, however, about variability in how these factors affect the development of RCC histologic subtypes. In this population‐based prospective cohort study, examination of variability in associations between established etiologic factors and RCC histologic subtypes revealed significant heterogeneity between BMI and ccRCC and pRCC risk and between risk of these subtypes and smoking duration in current smokers. The findings provide novel insight into relationships between etiologic heterogeneity and mechanisms of RCC development.

Dietary carbohydrates have long been expected to be associated with risk of type 2 diabetes; however, the associations for many carbohydrates and carbohydrate-rich foods remain inconclusive. This study analysed associations between intakes of six types of carbohydrates and thirteen carbohydrate-rich foods with incident type 2 diabetes in 26 622 participants (61 % women) in the Malmö Diet and Cancer Study in southern Sweden. Dietary intake was assessed at baseline (1991–1996) by using a modified diet history method. During mean follow-up of 18 years, 4046 cases were identified. Adjusting for potential confounders (including lifestyle, BMI and dietary factors), comparing highest v. lowest quintile of intake, monosaccharides (hazard ratio (HR) 0·88; 95 % CI 0·79, 0·98; Ptrend = 0·02) and fruits (HR 0·91; 95 % CI 0·82, 1·01; Ptrend = 0·03) were inversely associated with incident type 2 diabetes, while disaccharides (HR 1·17; 95 % CI 1·04, 1·30; Ptrend = 0·002) and sweets (HR 1·09; 95 % CI 1·00, 1·19; Ptrend = 0·02) were positively associated. After stratification by sex, marmalade/honey/jam (HR 0·82; 95 % CI 0·72, 0·94; Ptrend < 0·001) and vegetables (HR 0·85; 95 % CI 0·73, 0·98; Ptrend = 0·06) were inversely associated with incident type 2 diabetes in men and chocolate (HR 1·26; 95 % CI 1·09, 1·46; Ptrend < 0·001) was positively associated in women. In conclusion, we identified inverse associations for intake of monosaccharides and fruits with type 2 diabetes risk, and positive associations for disaccharides and sweets. Additional sex-specific associations were also identified. Future studies are needed to explore these associations further.

Purpose of review Dietary factors have been linked to cancers. This review focuses on several nutrients, which have strong evidence showing increase in cancer risks in the esophagus and stomach. Recent findings Obesity is an important risk factor in upper gastrointestinal cancers. High sugar content in food and sugary drinks are the main drivers of obesity. Proinflammatory diet is another dietary factor, which is increasingly recognized as being associated with esophageal and gastric cancer. Summary Cancer has been predicted to be the leading cause of death in this century. Cancers of the esophagus and stomach are the six and third most common cause of death worldwide. Although Helicobacter pylori infection is a known cause of gastric cancer, obesity is a leading contributor to esophageal adenocarcinoma. Epidemiological data have shown that dietary factors are associated with the two cancers. Observational, case control, animal and recent large cohort studies have identified associations between dietary factors and upper gastrointestinal cancer. Data are also emerging from studies, which look at dietary patterns, such as reduction in the Dietary Inflammatory Index, as well as adherence to a modified Mediterranean diet, and its association with the incidence of esophageal and gastric cancer.

Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly ( P

Purpose Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]). Conclusion High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes.

The importance of food contaminants in the link between diet and cancer has been widely demonstrated. Therefore, different physical and chemical strategies for the control of human exposure to such dietary carcinogens has been explored; however, most of these strategies are complex, costly, and have low efficiency which limited their applications. Hence, microbiological methods have been receiving more attention. Recent in vitro and in vivo studies have indicated that lactic acid bacteria (LAB) and yeast may act as dietary carcinogen-binding agents. This review describes the promising protective role of strains belonging mainly to the

Background: Iodine has been suggested to protect against breast cancer, but there are no epidemiologic studies on individual risk. An interesting finding is that in areas where the exposure to both selenium and iodine are high (e.g., Japan), the risk of breast cancer is lower than in areas where selenium is high and iodine low (e.g., United States), or in areas where both are low (e.g., Northern Europe). The aim of this study was to investigate the association between prediagnostic serum iodine levels and subsequent breast cancer risk, and to investigate if this potential association was modified by selenium levels. Methods: The Malmö Diet and Cancer Study provided prediagnostic serum samples and the current analysis included 1,159 breast cancer cases and 1,136 controls. Levels of baseline serum iodine and selenium were analyzed. A logistic regression analysis yielded ORs with 95% confidence intervals adjusted for potential confounders. Results: There was no evidence of an overall association between iodine levels and risk of breast cancer. Among women with high selenium levels (above the median), high iodine levels were associated with a lower risk of breast cancer; the OR for above versus below the median was 0.75 (0.57–0.99). The corresponding OR for women with low selenium was 1.15 (0.87–1.50), and the Pinteraction was 0.06. Conclusions: The combination of high serum iodine levels and high selenium levels was associated with a lower risk of breast cancer. Impact: A high iodine and selenium exposure may decrease the risk of breast cancer.

Women with lower levels of serum selenium (Se) may have a worse survival in breast cancer than women with higher levels, despite no difference in incidence of the disease. Our study was conducted to test whether Se is associated with the aggressiveness of breast tumors. Both the risk of having a tumor characteristic associated with worse prognosis, as well as the overall and breast cancer-specific mortality, were studied. We identified breast cancer cases and controls within the Malmö Diet and Cancer Study, a population-based cohort with 17 035 women recruited between 1991 and 1996. Inclusion criteria were incident breast cancer. Exclusion criteria were carcinoma in situ and bilateral breast cancer. Controls were selected among breast cancer-free women both from matching (n = 694) as well as randomization (n = 492). After exclusion, 1066 cases remained and were compared to controls regarding their prediagnostic serum Se levels and subsequent risk of having a certain tumor characteristic or intrinsic subtype. We also followed breast cancer patients regarding overall and breast cancer-specific mortality, comparing different Se quartiles. No association between serum Se quartile and any tumor characteristic or intrinsic subtype was found. Lower overall mortality was found among women in the highest Se quartile compared to the lowest using an adjusted Cox proportional hazards model, hazard ratio 0.63 (95% confidence interval: 0.44-0.89). Similar results were seen for breast cancer-specific mortality, 0.60 (0.37-0.98). The results of our study support that Se is associated with a lower mortality in breast cancer, not related to established prognostic factors.

Background Other than in work settings, much of our exposure to PAHs comes from food. Scope and approach Plants take up PAHs from contaminated soil and through settling of air particles on surfaces. The raw materials from these contaminated plants facilitates the presence of these compounds in derived food items such as cereals, grains, flour, bread, oils and fats, fruits and vegetables. Milk and meat products are affected by the accumulation of PAHs in fatty tissues of animals thriving on contaminated feed and breathing contaminated air. Fish and shellfishes (bottom-dwellers or filter-feeders) used as seafood accumulate these toxic compounds from contaminated water. Key findings and conclusions The heat-driven processing of these foods add-on PAHs when they are subjected to high temperatures, fire and fuels. Being carcinogenic compounds, it becomes necessary to understand the strategies which can be explored at public and commercial level to prevent or reduce the formation of PAHs during the processing of foods and reduce associated cancer risk.

Background: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk.Patients and methods: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models.Results: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI >= 35.0 kg/m(2) with 21-22.9 kg/m(2). When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI = 30.0 kg/m(2) at baseline compared with BMI = 110 cm with = 1.00 with = 1.90 m withConclusion: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

Background The evidence on the association between adherence to a healthy lifestyle and risk of glioma are scarce. This is particularly relevant to Middle Eastern countries where lifestyle factors including dietary intakes, physical activity and environmental contributors are different from other parts of the world. The aim of this case-control study was, therefore, investigating the association between adherence to a healthy lifestyle and odds of glioma among adults. Methods Totally, 128 newly diagnosed glioma cases and 256 age- and sex-matched controls were recruited in this hospital-based case-control study. Dietary intakes were examined by the use of a 126-item validated FFQ. International Physical Activity Questionnaire (IPAQ) was used for measuring physical activity of participants. To construct a healthy lifestyle score (HLS), data from dietary intakes, physical activity and BMI were used. Subjects in the low risk categories of the mentioned components received the score of 1, otherwise they received the score of 0. The final HLS was computed through summing up the scores of components. Results After adjustment for age and sex, we found that individuals with the highest HLS score were 55% less likely to have glioma compared with those with the lowest score (OR: 0.45; 95% CI: 0.22, 0.92). Additional controlling for other potential confounders made the association stronger (OR: 0.28; 95%CI: 0.12, 0.66). In terms of individual components of healthy lifestyle score, subjects with a healthy diet had 54% lower odds of glioma than those with a non-healthy diet (OR: 0.46; 95%CI: 0.26, 0.80). No significant associations were seen between physical activity level or BMI status and glioma. Conclusion We found evidence indicating that adherence to a healthy lifestyle, in particular a healthy diet, was associated with a lower odds of glioma. Prospective cohort studies are needed to confirm these findings.

Over the past decade, the search for dietary factors on which to base cancer prevention guidelines has led to the rapid expansion of the field of dietary patterns and cancer. Multiple systematic reviews and meta-analyses have reported epidemiological associations between specific cancer types and both data-driven dietary patterns determined by empirical analyses and investigator-defined dietary indexes based on a predetermined set of dietary components. New developments, such as the use of metabolomics to identify objective biomarkers of dietary patterns and novel statistical techniques, could provide further insights into the links between diet and cancer risk. Although animal models of dietary patterns are limited, progress in this area could identify the potential mechanisms underlying the disease-specific associations observed in epidemiological studies. In this Review, we summarize the current state of the field, provide a critical appraisal of new developments and identify priority areas for future research. An underlying theme that emerges is that the effectiveness of different dietary pattern recommendations in reducing risk could depend on the type of cancer or on other risk factors such as family history, sex, age and other lifestyle factors or comorbidities as well as on metabolomic signatures or gut microbiota profiles.

Background Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Methods Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Results Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2–4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5– Conclusions These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.

OBJECTIVE Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle. RESEARCH DESIGN AND METHODS At baseline, 178 lipids were measured by mass spectrometry in 3,668 participants without diabetes from the Malmö Diet and Cancer Study. The population was randomly split into discovery (n = 1,868, including 257 incident cases) and replication (n = 1,800, including 249 incident cases) sets. We used orthogonal projections to latent structures discriminant analyses, extracted a predictive component for T2DM incidence (lipid-PCDM), and assessed its association with T2DM incidence using Cox regression and lifestyle factors using general linear models. RESULTS A T2DM-predictive lipid-PCDM derived from the discovery set was independently associated with T2DM incidence in the replication set, with hazard ratio (HR) among subjects in the fifth versus first quintile of lipid-PCDM of 3.7 (95% CI 2.2–6.5). In comparison, the HR of T2DM among obese versus normal weight subjects was 1.8 (95% CI 1.2–2.6). Clinical lipids did not improve T2DM risk prediction, but adding the lipid-PCDM to all conventional T2DM risk factors increased the area under the receiver operating characteristics curve by 3%. The lipid-PCDM was also associated with a dietary risk score for T2DM incidence and lower level of physical activity. CONCLUSIONS A lifestyle-related lipidomic profile strongly predicts T2DM development beyond current risk factors. Further studies are warranted to test if lifestyle interventions modifying this lipidomic profile can prevent T2DM.

Objective:To determine the level of adherence and to assess the association between higher adherence to the South African food based dietary guidelines (SAFBDG) and breast cancer risk.Design:Population-based, case–control study (the South African Breast Cancer study) matched on age and demographic settings. Validated questionnaires were used to collect dietary and epidemiological data. To assess adherence to the SAFBDG, a nine-point adherence score (out of eleven guidelines) was developed, using suggested adherence cut-points for scoring each recommendation (0 and 1). When the association between higher adherence to the SAFBDG and breast cancer risk was assessed, data-driven tertiles among controls were used as cut-points for scoring each recommendation (0, 0·5 and 1). OR and 95 % CI were estimated using multivariate logistic regression models.Setting:Soweto, South Africa.Participants:Black urban women, 396 breast cancer cases and 396 controls.Results:After adjusting for potential confounders, higher adherence (>5·0) to the SAFBDG v. lower adherence (4·5) of the SAFBDG.Conclusions:Higher adherence to the SAFBDG may reduce breast cancer risk in this population. The concerning low levels of adherence to the SAFBDG emphasise the need for education campaigns and to create healthy food environments in South Africa to increase adherence to the SAFBDG.

Background: Whether high dairy consumption is related to longevity is still unclear, and additional studies of prospective cohorts with high-quality dietary data from populations with wide consumption ranges are needed.Objective: To examine the association between dairy consumption and mortality in a Swedish cohort.Design: Among 26,190 participants (62% females, 45–73 years old) without diabetes and cardiovascular disease from the population-based Malmö Diet and Cancer cohort, 7,156 individuals died during a mean follow-up time of 19 years. Data on intake of dairy (non-fermented milk, fermented milk, cheese, cream and butter) were collected from 7 day food records and food questionnaires. A genetic marker (rs4988235) associated with lactase persistence was detected among 22,234 individuals born in Sweden.Results: Higher intakes up to 1,000 g/day of non-fermented milk were associated with only marginal higher mortality rates after adjusting for potential confounders. However, intakes above 1,000 g/day (1.5% of the population) were associated with 34% (95% CI: 14, 59%, p-trend=0.002) higher mortality compared to that with < 200 g/day. Fermented milk and cheese intake were inversely associated with mortality. Cream showed a protective association only among men. Butter was not associated with mortality. CT/TT genotype carriers (i.e., individuals with lactase persistence) had a 27% higher reported consumption of non-fermented milk, and non-significant higher mortality risk (HR = 1.08; 95% CI = 0.96, 1.23; p = 0.20) than CC genotype carriers.Conclusions: Higher mortality rates were mainly observed among participants consuming more than 1,000 g of non-fermented milk per day. In contrast, fermented milk and cheese were associated with lower mortality. Because dairy products differ in composition, it is important to examine them separately in their relation to health and disease. The use of a genetic variant as an objective marker of lactose-containing milk intake should be examined in relation to mortality in a larger population.

Background The association between leisure-time physical activity and cardiovascular mortality has been previously studied, but few studies have focused on specific activities and intensities. Methods The association between different leisure-time physical activities and cardiovascular mortality was investigated among 25,876 individuals without diabetes or cardiovascular disease from the population-based Malmö Diet and Cancer Study cohort. The individuals estimated the average duration spent on 17 physical activities at baseline in 1991–1996 and after 5 years. Cardiovascular mortality was obtained from a register during a mean of 20 years of follow-up. Results A total leisure-time physical activity of 15–25 metabolic equivalent task (MET) hours/week was associated with a decreased risk of cardiovascular mortality (HR 15–25 vs Conclusions Moderate- and high-intensity leisure-time physical activities reduced the risk of cardiovascular mortality. With regard to total leisure-time physical activity, the largest risk reduction was observed for 15–25 MET-h/week (equivalent to walking for approximately 5 h/week).

Background Current global food systems threaten human health and environmental sustainability. In 2019, the EAT-Lancet Commission on healthy diets from sustainable food systems defined the first global reference diet to improve both areas, but there is no consensus on how to quantify the EAT-Lancet reference diet as a diet index and its relation to mortality has not been widely studied. Objective To develop a new dietary index to quantify adherence to the EAT-Lancet diet and assess its association with mortality in a large population-based Swedish cohort. We also examined food components included in the index and their individual associations with mortality. Design We used the Malmo Diet and Cancer cohort (n = 22,421, 45-73 years at baseline). Dietary data were collected using a modified diet history method. The EAT-Lancet index was developed based on intake levels and reference intervals of 14 food components defined in the EAT-Lancet diet (0-3 points per component, 0-42 points in total). Associations with mortality were examined based on registers during a mean of 20 years of follow-up and were adjusted for potential confounders. Results Divided into five adherence groups, the highest adherence to the EAT-Lancet diet (≥23 points) was associated with lower all-cause mortality (HR: 0.75; 95% CI: 0.67, 0.85), cancer mortality (HR 0.76; 95% CI: 0.63, 0.92) and cardiovascular mortality (HR 0.68; 95% CI: 0.54, 0.84) than the lowest adherence (≤13 points). Several food components included in the index contributed to the observed reductions in mortality. Conclusions We developed a new dietary index to investigate adherence to the EAT-Lancet diet. The findings indicate a 25% lower risk of mortality among those with the highest adherence to the EAT-Lancet diet, as defined using our index, which adds to the evidence base for the development of sustainable dietary guidelines.

This chapter reviews the Epidemiology of Nutrition, Diet, and Cancer Risk from observational data on the association between nutrients, dietary patterns, and the risks of common forms of cancer and discusses potential causal inferences and possible nutritional intervention strategies for cancer prevention and control. There are two major aspects in nutrition and cancer, identifying carcinogenic and anticarcinogenic effects from dietary patterns, components, chemicals, nutrients for reduction of cancer risk, and improvement of clinical outcomes. Following successes in identifying the causal association of tobacco smoking with lung cancer, epidemiologists in the 1960s began to seriously examine associations of diet, nutrition, and cancer risk. The Bradford-Hill criteria were established in 1965 and are the most widely referenced criteria for establishing causal inferences from epidemiological data. The identification of aflatoxin B1 from diet as a group 1 carcinogen is a typical application of causal inference using the Bradford-Hill criteria in nutritional epidemiology. These criteria were developed during an early era of epidemiology when many modern advances in genetics, molecular biology, toxicology, exposure science, and statistics had not yet occurred. Many recent scientific advances have increased the options for the exploring potential cause-and-effect relationships in diet, nutrition, and cancer risk using modern epidemiological methods combined with insights from molecular biology, precision oncology, and personalized nutrition. Epidemiological research has traditionally formed the basis for dietary guidance issued by cancer organizations and government panels. As new science is integrated into epidemiology, the recommendations made are likely to be improved and made more specific. Currently, cancer prevention guidelines advocate a diet rich in fruits, vegetables, and whole grains, suggest limiting sugary foods and beverages, red and processed meats, sodium, and alcohol, and recommend avoiding foods contaminated with carcinogens. Some dietary supplements such as vitamins, minerals, and green tea have also been examined in research studies but have not been widely recommended despite their frequent use by many healthy individuals and cancer patients. Overweight and obesity-associated metabolic abnormalities are increasing around the world that are associated with cancer risk, due to overconsumption of energy-dense, high fat, glycemic load, sugary, and salty foods. Typically, individuals following a modern diet do not meet daily recommendations for fruit, vegetable, or whole grain consumption. While there is much more to learn about personalized nutrition and precision oncology, the recommendations that have emerged from decades of epidemiological research into the connections between nutrition and cancer form a valuable store of information that can be expanded as our understanding of carcinogenesis continues to evolve with new research. Over the past decades, a number of large intervention studies using a randomized controlled trial design have attempted to obtain final proof of a nutrient-cancer causal relationship. For many reasons, some of these large trials have failed to demonstrate the benefit of nutritional intervention because of the chosen endpoints, limited dose levels, and short duration. These results were at odds with the epidemiological data which inspired them. Results of some large trials have confused the public and led to press reports questioning any relationship of nutrition to cancer. A new approach is clearly needed where epidemiology provides part of the overall evidence. In this chapter, we recommend a research strategy that can integrate information from laboratory and animal studies to lead to common sense public health recommendations that are feasible and acceptable by public.

With the growing interest in studying the role of soluble urokinase plasminogen activator receptor (suPAR) in kidney and other diseases, levels are now being measured in major cohorts across the world through various methods, including immunoassays and through proteomics. Reported suPAR values have however varied dramatically depending on which assay is used. Comparing suPAR assays and their ability to discriminate risk is crucial for the Nephrology and overall research community to guide assay choice and inform interpretation of findings. To that end we measured suPAR in 3 different major cohorts (Malmo Diet and Cancer Study, n=4637; Jackson Heart Study, n=1905; and the Emory Cardiovascular Biobank, n=487) using two different methods in each cohort, encompassing the most commonly used approaches (immunoassays and proteomics). We find dramatic differences between assays; with notably poor correlations between immunoassays and proteomic approaches (r=0.2-0.5). Proteomics-based suPAR measures very poor discriminatory ability for cardiovascular and incident kidney disease. Amongst the immunoassays, the suPARnostic assay reported the highest values and had the strongest discriminatory ability.

OBJECTIVES: Advanced glycation end products (AGEs) are reactive metabolites formed endogenously by glyoxidative, oxidative and lipoxidative stresses. Foods associated with modern dietary habits are particularly AGE laden but despite increasing epidemiological evidence for oncogenic potential, cause and effect relationships are lacking. The objective was to provide detailed mechanistic insight and in vivo confirmation that AGEs found in the diet are oncogenic drivers of tumorigenesis. METHODS: We used the heat driven formation of glyoxidative, oxidative and lipoxidative stresses in experimental mouse chow to reproduce the wide spectrum of the AGEs found in vivo. Syngeneic xenograft and spontaneous prostate and breast cancer mouse models were then fed the AGE specific diets and the effects of chronic AGE consumption on tumor growth assessed. To gain mechanistic insight, human and mouse two compartment co-culture models using primary fibroblasts and matched tumor epithelial cells were then used to assess the effects of AGEs on extracellular crosstalk in the TME. RESULTS: A high impact finding from our research is that consumption of AGEs found in our diet promotes prostate tumor growth, aggression and metastasis by functioning as ligand to the transmembrane receptor for AGE (RAGE). Dietary-AGEs promoted neoplastic growth by functioning as ligand to RAGE expressed in the prostate tumor stroma not tumor epithelium. Dietary-AGE activation of stromal RAGE caused a regulatory program of ‘activated fibroblasts’ defined by the increased expression of cancer associated fibroblast markers, NFkB, MYC and pro-tumorigenic paracrine secretion. Fibroblast activation was accompanied by decreased expression of androgen receptor (AR) and the increased expression of neuroendocrine differentiation markers in tumor epithelial cells. AGE exposed primary fibroblasts isolated from patient tissue conferred tumor promoting abilities when cultured with patient matched tumor epithelial cells. CONCLUSIONS: For the first time these data demonstrate a direct cause and effect relationship between dietary-AGEs and neoplastic growth. This may lay the foundation for strategic self-management strategies aimed at reducing AGE exposure in the diet to reduce cancer incidence and mortality. FUNDING SOURCES: NIH/NCI; ACS.

OBJECTIVES: The F1Fo ATP synthase is a multienzyme complex that produces mitochondrial ATP. Aberrant expression or assembly of F1Fo ATP synthase subunits leads to alterations in energy metabolism. We recently found that breast cancer cells exposed to fluid shear stress (FSS) have significantly enhanced metastatic behavior including chemoresistance and cell proliferation. Chemoresistance depends upon active transport systems, and cell division and growth require ATP. Therefore, we hypothesized that circulating breast cancer cells undergo altered energy metabolism via FSS-induced changes in F1Fo ATP synthase subunits and subsequent mitochondrial remodeling. METHODS: Non-metastatic MCF7 and metastatic MDA-MB-231 human breast cancer cells were treated with or without FSS and cultured. Cellular proliferation was assayed by measuring cell number and gap distance. Metabolic profile including intracellular ATP and oxygen consumption rate were analyzed. We also quantified abundance of F1Fo ATP synthase subunits using immunoblotting. RESULTS: Treatment with FSS significantly increased proliferation of both MCF7 and MDA-MB-231 human breast cancer cells. FSS significantly increased intracellular ATP in MDA-MB-231 breast cancer cells while ATP levels in MCF7 were not significantly changed. MDA-MB-231 cells retained increased ATP after treatment with the uncoupler FCCP, indicating remodeling and decreased reliance on mitochondrial energy metabolism. Interestingly, oxygen consumption rate was significantly increased in both MCF7 and MDA-MB-231 by FSS. We further quantified the abundance of F1Fo ATP synthase subunits in both cell lines. The β- and c-subunits of the F1Fo ATP synthase were significantly depleted in both lines of FSS-treated breast cancer cells. CONCLUSIONS: Our data show that FSS alters abundance of the F1Fo ATP synthase subunits leading to metabolic remodeling. We suggest that FSS may influence non-metastatic (MCF7) and metastatic cancer cells (MDA-MB-231) differently. Underlying changes in mitochondrial and cytoplasmic ATP production in these cells is still under investigation. However, it is possible that reactive oxygen species generated during FSS may signal a switch to cytoplasmic intracellular energy metabolism. FUNDING SOURCES: Alabama Life Research Institute Pilot Project (University of Alabama)

OBJECTIVES: Monitoring psychosocial, emotional, and hedonic aspects of food behavior is important to understand cancer patients’ distress and help to reduce risks of malnutrition. However, to date, there is no specific tool to measure the impact of diet, eating behavior, and chemotherapy side effects on patients’ food-related quality of life during cancer and its treatments. The objective was to develop and validate a questionnaire that aims to assess the food-related quality of life in cancer patients undergoing chemotherapy. METHODS: Relevant items from the existing food-related quality of life assessment tools were selected to compose the present 46-item questionnaire. The validation of the questionnaire was conducted in 276 healthy volunteers and 173 cancer patients. Exploratory Factor Analysis (EFA) was performed in both groups, construct and discriminant validity, and test-retest reliability were calculated. RESULTS: The questionnaire was perceived as clear and required less than14 minutes for completion (93% complete responses) in a pre-test (n = 156). The EFA allowed the inclusion of 9 dimensions in the food-related quality of life questionnaire. Common patterns between patients and healthy volunteers (factor loadings ≥ 0.4 in both groups) were used to calculate scores by dimension. Scores in the dimensions of adapting diet and sensorial discomfort (taste/odor) were higher in cancer patients, whilst scores in the dimension of discomfort in satiety were higher in healthy volunteers. Among patients with cancer, the total scores in sensorial discomfort, digestive discomfort, and discomfort in satiety were higher under chemotherapy than no treatment. Reproducibility after one week was in increasing order; digestive discomfort 0.6, adapting diet 0.61, products’ quality 0.67, cooking 0.75, healthy diet 0.76, eating and pleasure 0.80, discomfort in satiety 0.82, and sensorial discomfort 0.85. CONCLUSIONS: This 46-item questionnaire can discriminate cancer patients versus healthy volunteers, and patients receiving vs those not receiving chemotherapy. A good to very good reproducibility was found for the most important factors of food-related quality of life of patients with cancer, i.e, eating and pleasure, sensorial discomfort, and discomfort in satiety. FUNDING SOURCES: This study is funded by La Région Auvergne Rhône-Aples and La Métropôle de Lyon.

OBJECTIVES: The objective of this study was to investigate the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa. We hypothesized that TP would be protective against PCa growth. METHODS: Diets (either CON [17.2% kcal from fat] or OB [44.6% kcal from fat] both with and without 10% TP) were fed to transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (n = 5/dietary group) from weaning. Tumor growth was monitored by weekly ultrasound scanning, at which time novel ultrasound microvessel images (UMI) were captured to quantitatively measure tumor blood perfusion over time. Animals were euthanized after 5 weeks of tumor growth, and tissues were collected for measurement of protein (HIF-1α, TNFα) and gene (ar, srd5a1, srd5a2) expression. Data were analyzed to determine differences between CON diets (without TP + with 10% TP) and OB diets (without TP + with 10% TP) and to evaluate the impact of 10% TP on outcome measures both independent of TP (No TP vs. TP) as well as within CON and OB diets (interaction effect of diet(*)TP) by mixed model ANCOVA with body weight as a covariate. RESULTS: UMI results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively and longitudinally monitor tumor blood perfusion in vivo. Greater body weight (P = 0.029) and OB diets (P = 0.008) were associated with earlier age at tumor detection, and greater body weight was positively associated with tumor growth (P = 0.001). TP significantly inhibited prostate tumor angiogenesis (P = 0.043), but this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth (P = 0.004), intratumoral inflammation (TNFα; P = 0.019), and intratumoral androgen-regulated gene expression (srd5a1, srd5a2; P = 0.030 and P = 0.016, respectively) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. CONCLUSIONS: Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet. FUNDING SOURCES: CA was supported by the NIH NIBIB. MRL and PS were partially supported by NIH NCI.

OBJECTIVES: To systematically review the published evidence on nutritional risk screening instruments, nutritional assessment and functional capacity used in hospitalized cancer patients and possible associations with unfavorable clinical outcomes. METHODS: A systematic search was performed in EMBASE, PubMed/MEDLINE, LiLACS and SciELO (publications from January 2010 to January 2021) databases by search terms related to “nutritional risk”, “nutritional assessment”, functional capacity” and “cancer”. RESULTS: 3753 articles were identified, and 321 duplicates were excluded. Of the 3432 articles analyzed by title/abstract, 109 were selected for full reading and 28 studies meeting the inclusion criteria. The agreement analysis between the researchers generated a Kappa of 0.813. The evaluated studies included comparison of tools: 1) nutritional screening, 2) nutritional screening based on laboratory parameters, 3) nutritional assessment, 4) nutritional diagnosis and, 5) functional capacity. The higher nutritional risk, worst nutritional status and low functional capacity assessed by the Nutritional Risk Screening 2002 (NRS- 2002), Patient-Generated Subjective Global Assessment (PG-SGA); Subjective Global Assessment (SGA) and lower handgrip strength, respectively, were associated with longer of hospital stay. The worst nutritional status, identified by the SGA scores, Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Index (NRI) were significant predictors of postoperative mortality. CONCLUSIONS: The studies included in this systematic review showed that higher nutritional risk, worse nutritional status and low functional capacity are associated with unfavorable outcomes such as longer hospital stay and mortality. The combination of the tools can be recommended for a complete assessment of the nutritional status of hospitalized cancer patients. FUNDING SOURCES: Fundo de Incentivo à Pesquisa (FIPE) do Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil. (number# 2019/0708).

OBJECTIVES: Determine the extent to which diets with higher fiber intakes (g) at baseline are independently associated with cancer development by final study visit in a cohort of rural post-menopausal women. METHODS: This study was a secondary analysis of participants in a four-year randomized controlled trial evaluating the effect of vitamin D and calcium supplementation (2000 IU/d vitamin D3 and 1500 mg/d calcium) on cancer development in rural post-menopausal women in Nebraska (June 2009-August 2015). Diets, including fiber intake (total, soluble, fruit-vegetable, grain and bean fiber), were evaluated via a 2005 Block Food Frequency Questionnaire at baseline. T-tests were used to evaluate the difference in dietary fiber intakes between all-type cancer and non-cancer groups. Logistic regression models, controlling for pertinent covariates, were used to determine if dietary fiber intake at baseline is associated with the cancer development. Dietary fiber variables were log-transformed and stratified by treatment group. RESULTS: There were 1977 participants available for analysis. Median total fiber intake was 14.35 g or 65% of the Dietary Reference Intake. There was no significant difference between dietary fiber intakes at baseline between the cancer group and non-cancer group. For people on vitamin D and calcium supplementation, higher dietary soluble fiber and fruit-vegetable fiber intakes at baseline were protective against cancer development [Soluble OR: 0.50; 95% CI (0.26, 0.96); Fruit-vegetable OR: 0.56; 95% CI (0.33, 0.94)]. In participants without vitamin D and calcium supplementation, the odds of having higher bean fiber intake was 1.62 times higher in those with cancer [OR: 1.62 (95% CI (1.07, 2.47)]. Total fiber and grain fiber intakes were not significantly associated with cancer development. CONCLUSIONS: While low fiber intake is prevalent among rural post-menopausal women, those with higher intakes of soluble and fruit-vegetable fiber may be more protected against development of all-type cancer when supplemented with calcium and vitamin D. Further analysis should examine the relationship between supplementation and bean fiber intake on the development of cancer. FUNDING SOURCES: The original study was funded by the National Cancer Institute and Creighton University internal funding. No additional funding was used for the secondary analysis.

OBJECTIVES: Colorectal cancer (CRC) is one of the most prevalent cancer worldwide. Evidence from epidemiological studies shows that the incidence rate of CRC among elders with age ≥ 50 years is gradually decreased, whereas the rate continuously rise in adults with age