A case-control study was conducted from July 2010 to April 2019, in Guangzhou, China. A total of 2502 eligible cases were recruited along with 2538 age-  and sex-matched controls. Dietary data derived from a validated food frequency questionnaire were used to calculate the energy-adjusted DII (E-DII) scores. Odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer risk were estimated using unconditional logistic regression models. In this study, E-DII scores ranged from −5.96 (the most anti-inflammatory score) to +6.01 (the most pro-inflammatory score). A positive association was found between the E-DII and colorectal cancer risk, with the OR = 1.40  for the highest E-DII quartile compared with the lowest quartile after adjusting for potential confounders. When stratified based on cancer subsite, sex, body mass index, and smoking status, significant associations were not observed in women or underweight individuals. Results from this study confirmed that a higher E-DII score was associated with an increased risk of colorectal cancer in a Chinese population.Diet may modulate chronic inflammation. The aim of this study is to investigate whether the dietary inflammatory index (DII Colorectal cancer is a common cancer around the world, with 1.8 million new cases estimated to have occurred worldwide in 2018 . It is aDietary factors may modulate chronic inflammation ,8. For e®) is a literature-derived, population-based scoring system that was developed to quantify the inflammatory potential of overall diet in diverse populations [The dietary inflammatory index  and sex. There are two control groups in this case-control study. The first control group was selected from patients who visited the first affiliated hospital of Sun Yat-sen University during the same period, with ear-nose-throat diseases, eye disorders, facial paralysis, orthopedic conditions, degenerate joint diseases, and varicose veins. A total of 1533 hospital-derived controls were invited in this study and 1357 were successfully interviewed, yielding a response rate of 88.51%. The second group of 1181 community-derived controls was recruited in Guangzhou and Shenzhen via referrals, invitation, and advertisements.The study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The protocols and procedures of this study were approved by the Ethical Committee of School of Public Health, Sun Yat-sen University. All participants in this study signed the informed consent form before the interview.2). All subjects were categorized into three groups based on BMI range of Chinese population: underweight (BMI < 18.5 kg/m2), normal weight (18.5 kg/m2 ≤ BMI < 24 kg/m2), overweight/obese (BMI ≥ 24 kg/m2) [A face-to-face interview was conducted by trained researchers using standardized questionnaires to collect data on socio-demographic characteristics, lifestyle factors , first-degree relatives with cancer, history of diabetes mellitus and inflammatory diseases , body height and weight. For women, information on menopausal status also was obtained. In this study, subjects were classified as nonsmokers and ever smokers (including regular smokers and former smokers). A regular smoker is defined as someone smoking at least 1 cigarette per day for more than 6 consecutive months, while former smokers are defined as those who reported being regular smokers in the past, but not having smoked in the past six months. Passive smoking is defined as being exposed to the tobacco smoke of others for at least 5 min per day during the previous 5 years. Regular drinkers are defined as subjects who drank alcohol at least once per week in the past year. Physical activity consisted of two parts: occupational activity and household and leisure-time activity. Occupational activity was grouped into nonworking, sedentary, light occupation, moderate occupation and heavy activity occupation according to labor intensity. Household and leisure-time activity is classified as follows: (a) light physical activity; (b) moderate physical activity; (c) vigorous physical activity . Informa4 kg/m2) .A reproducible and validated food frequency questionnaire (FFQ) was used to assess the participants’ daily consumption of various foods . DetaileDietary data derived from the FFQ were used to calculate the energy-adjusted dietary inflammatory index (E-DII) scores. The development of the DII has been described in detail elsewhere . In shorFor this study, the following 34 food items were used for calculating E-DII scores: carbohydrate, protein, total fat, fiber, saturated fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), n-3 PUFA, n-6 PUFA, cholesterol, thiamin, riboflavin, niacin, folic acid, vitamin B6, vitamin B12, vitamin A, vitamin C, vitamin D, vitamin E, β-carotene, iron, magnesium, selenium, zinc, flavan-3-ol, flavone, flavonols, flavonones, anthocyanidins, isoflavones, garlic, onion, and pepper.® 22.0. Differences between cases and controls were assessed using the Student’s t test or the Wilcoxon rank-sum test for continuous variables, and the χ2-test for categorical variables. The Kruskal–Wallis test for continuous variables was used to examine intakes of 34 food parameters according to quartile of the E-DII score. The E-DII was analyzed both as a continuous variable and a categorical variable; i.e., as quartiles based on the distribution in controls [All analyses were performed using SPSScontrols . The lowOf the 2502 cases, 1425 were men while 1077 were women; 1565 were diagnosed with colon cancer and 937 were diagnosed with rectal cancer. The socio-demographic characteristics of the subjects are shown in In this study, E-DII scores ranged from −5.96 (the most anti-inflammatory score) to +6.01 (the most pro-inflammatory score), and cases had a higher mean E-DII score (−0.50) compared with controls (−0.78). The distribution of 34 food parameters across quartiles of the E-DII among control subjects is presented in Ptrend < 0.01). Subgroup analysis by cancer site showed that diet-related inflammation is associated with increased colorectal cancer risk in both colon and rectal cancer, with adjusted ORs for the highest quartile compared with the lowest were 1.32  for colon cancer, 1.53  for rectal cancer, respectively.As shown in Q4 vs. Q1 1.74; 95% CI 1.35, 2.24; Ptrend < 0.01). In women, a marginally significant positive association was found . However, the interaction between the E-DII and sex in the risk of colorectal cancer was non-significant (Pinteraction = 0.52). When stratified based on BMI, higher E-DII scores were associated with increased colorectal cancer risk among normal weight and overweight and obese participants. Adjusted ORs for the highest quartile of the E-DII score relative to the lowest were 1.32  for persons with normal weight and 1.49  for persons with overweight or obesity; no statistically significant result was found in underweight people  (Pinteraction = 0.03). The results of stratified analysis by smoking status were similar to the main analysis in all study subjects. A stronger positive association was found between the E-DII score and colorectal cancer risk among ever smokers and non-smokers, with adjusted OR of 1.74  and 1.34 , respectively, comparing the highest with the lowest quartile. There was no statistically significant interaction between the E-DII and smoking status (Pinteraction = 0.25)  .This large case-control study focused on the relationship between E-DII score and colorectal cancer risk. The results showed that a more pro-inflammatory diet, as reflected by a higher E-DII score, was associated with an increased risk of colorectal cancer. These findings persisted after adjusting for various confounding factors. Chronic inflammation might be causally linked to the development of carcinogenesis through complicated molecular pathways ,3. PreviQ5 vs. Q1 1.16; 95% CI 0.97, 1.69). The present study provides evidence regarding the association between a higher E-DII score and an increased risk of colorectal cancer in a Chinese population. In concordance with this result, previous epidemiologic studies observed significant positive association between the DII and colorectal cancer risk ,31,32,33There are several mechanistic explanations for the role of diet-related inflammation in colorectal carcinogenesis. First, the pro-inflammatory potential of diet may contribute to insulin resistance by increasing chronic inflammation , which cThere are differences between colon and rectal cancer in etiology and pathologic characteristics, as well as genetic abnormalities . In the Q4 vs. Q1 1.44; 95% CI 1.29, 1.61 for men; and ORQ4 vs. Q1 1.12; 95% CI 0.95, 1.31 for women) [In the present study, the positive association between the E-DII and colorectal cancer risk was restricted to men. In women, we observed a similar tendency toward increased risk with higher E-DII scores, but results did not achieve statistical significance; perhaps due to reduced power because of smaller sample size. The National Institutes of Health-American Association of Retired Persons Diet and Health Study also found a statistically increased risk of colorectal cancer with a higher DII score in men, but not in women (ORr women) . The difr women) . Based or women) ,51.Stratified analysis based on BMI status showed that the positive association of the E-DII score with colorectal cancer risk was stronger in overweight and obese individuals as compared to normal-weight individuals, suggesting that the association may be reinforcing obesity-related inflammation. One of the possible mechanisms for the relationship between obesity, inflammation, and colorectal cancer risk can be explained by the release of inflammatory factors by adipose tissue-derived cell types, including macrophages and adipocytes . ObesitySmoking is associated with a wide range of alterations in inflammatory marker levels and smoking-induced inflammation may be a critical mechanism in cancer development . In the The present study has several strengths. This is the first epidemiologic study to investigate the association between the inflammatory potential of diet and colorectal cancer risk in China, which has different dietary patterns and high colorectal cancer incidence. The sample size was relatively large relative to other case-control studies. Generally, study participants did not know the inflammatory potential of different foods, and the hypothesis of our research also was not revealed to all study subjects, thereby minimizing information bias. Moreover, several potential confounders, including socio-demographic characteristics and lifestyle factors, were adjusted when assessing the association between the E-DII and colorectal cancer risk.This study also has some limitations. First, selection bias is potential limitation in case-control studies. All cases were recruited from Sun Yat-sen University Cancer Center, the biggest cancer center in Southern China. However, the clinical characteristics of colorectal cancer patients in this center were similar to those of patients from other large hospitals in Guangdong province  or in maIn conclusion, a higher E-DII score was associated with an increased risk of colorectal cancer among Chinese population, suggesting a potential role of diet-related inflammation in colorectal carcinogenesis. Results from this important study in a unique Chinese population add to the impressive list of others that previously examined the role of diet-related inflammation in colorectal carcinogenesis and are now part of the established literature on the subject.