Association of retinol and carotenoids content in diet and serum with risk for Colorectal cancer: a meta-analysis

doi:10.21203/rs.3.rs-1553815/v1

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Research Article

Association of retinol and carotenoids content in diet and serum with risk for Colorectal cancer: a meta-analysis

https://doi.org/10.21203/rs.3.rs-1553815/v1

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posted 20 Apr, 2022

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Background: Colorectal cancer (CRC) risk is linked to serum and dietary retinol and carotenoids, according to clinical and epidemiological research. However, the findings are not consistent. As a result, we did this meta-analysis to determine the link between them.

Methods: From 2000 through 2022, the PubMed, Web of Science, and Embase databases, as well as pertinent article references, were searched and filtered based on inclusion and exclusion criteria and literature quality ratings. High and low intake were used as controls, and OR (odds ratio) or RR (relative risk) and 95% confidence interval were extracted. The extracted data were plotted and analyzed using Stata12.0 software.

Results: A total of 22 relevant studies were included, including 18 studies related to diet and 4 studies related to serum. For high and low intake or concentration controls, the pooled OR was as follows: β-carotene (OR = 0.89, 95% CI: 0.78-1.03), α-carotene (OR = 0.87, 95% CI: 0.72 – 1.03), lycopene (OR = 0.93, 95% CI: 0.81 – 1.07), lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87 – 1.07), β-cryptoxanthin (OR = 0.70, 95% CI: 0.54 – 0.90), total carotenoids (OR = 0.97, 95% CI: 0.81-1.15), retinol (OR = 0.99, 95% CI: 0.89 – 1.10)，serum carotenoids (OR = 0.73, 95% CI: 0.58 – 0.93), serum retinol (OR = 0.62, 95% CI: 0.26 – 1.49). Subgroup analysis was performed according to tumor type, study type and sex.

Conclusions: Dietary intake of β-cryptoxanthin significantly reduced CRC risk and dietary β-carotene considerably decreased CRC risk in the male group. Alternatively, serum carotenoid concentrations were significantly inversely associated with CRC risk.

retinol

carotenoids

diet and serum

colorectal cancer

meta-analysis

In recent years, the incidence and mortality of malignant tumors have been increasing year by year, even exceeding other chronic diseases, becoming a veritable human health killer(1). Despite the fact that cancer efficacy has improved dramatically as a result of integrated therapies such as surgery, chemotherapy, radiation, targeted therapy, and immunotherapy, prognosis and early diagnosis remain poor, and the death rate remains high(2). Colorectal cancer (CRC) is the world's third most frequent disease and the second largest cause of cancer mortality, with a significant number of new cases and deaths every year (3).CRC has caused great burden and harm to the economy and society of the country(4). Economic development and changes in lifestyle and dietary choices have increased the prevalence and mortality of CRC in China in recent years, putting a strain on the health-care system (3, 5). The etiology of CRC is heavily influenced by environmental and genetic factors. Diet, history of benign adenomatous polyps and inflammatory bowel disease, age, diabetes, obesity, lack of physical activity, and a family history of CRC diet are all risk factors for CRC(6). Therefore, the prevention of CRC by changing dietary habits and lifestyle is an area that we should focus on.

Fruits and vegetables are among the daily foods required for good health since they include high levels of minerals, vitamins, carbs, proteins, dietary fiber, and different substances with nutritional medicinal value that can help prevent a variety of ailments(7). Many studies have indicated that eating fruits and vegetables helps prevent cancer, with vegetable-related protection being more substantial(8, 9).Vitamin A is an unsaturated hydrocarbon group that includes retinol and its derivatives such as retinaldehyde, retinoic acid, and retinyl ester(10). Cell development and differentiation, embryogenesis, reproduction, epithelial cell integrity, and immunological function are all regulated by vitamin A(11, 12). It also has antioxidant properties(13) and helps to reduce oxidative stress damage and inflammation (11, 14). Carotenoids are a good source of vitamin A and may be turned into it by the body(15). Carotenoids are natural pigments found in a wide range of fruits and vegetables, including lycopene, β-carotene, lutein, zeaxanthin, and β-cryptoxanthin(16). Carotenoids and retinoids share many biological actions, including antioxidant capabilities, suppression of malignant tumor development, and activation of apoptosis(17). Carotenoids can influence cell development, as well as gene expression and immunological responses(18, 19). Thus, retinol and carotenoids are indispensable in the human body. But retinol cannot be synthesized in the human body, and it must be obtained from the diet(20). As a result, research into the relationship between their consumption and human illnesses, including cancer, is required.

Over the last two decades, researchers have conducted substantial research on the link between nutrition and cancer. Epidemiological studies have found a link between food and cancer incidence and aggressiveness (21). A high intake of dietary carotenoids or vitamin A (retinol) has been linked to a decreased risk of colorectal cancer in several studies (22–25). Other studies, however, have shown no substantial link between their use and the risk of cancer onset(25–27). Surprisingly, there has been interest in the research of serum retinol and carotenoids, and some studies have shown that their levels in the blood are related to the risk of colon cancer. As a result, we completed our meta-analysis in time to incorporate the most recent relevant data, providing more credible scientific support for CRC prevention.

Search strategy for literature

Two writers (Xiaoyong Han and Rangyin Zhao) separately conducted a literature search for the association between retinol, carotene, and related derivatives and the risk of CRC in humans using the PubMed, Web of Science and Embase databases. The following keywords were used in the search: “retinol” or “carotenoids” or “carotene” or “β-carotene” or “cryptoxanthin” or “lycopene” or “lutein” or “zeaxanthin” combined with “Colorectal cancer” or “colon cancer” or “rectal cancer”. All relevant literature was searched from 2000 to 2022. In addition, we performed a manual search of the reference lists of reviews, meta-analyses, and other relevant publications to prevent potentially missed articles. The language of included articles was limited to English.

Inclusion and exclusion criteria

Studies were included according to the following criteria: (1) patients were diagnosed with colon or rectal cancer; (2) observational studies, including cohort or case-control studies; (3) The associations of interest are about the association of serum or dietary retinol or carotenoids with CRC risk, and there are comparisons of high and low content.; (4) relative risk (RR) or odds ratio (OR) with 95% confidence interval for cancer-containing. The following exclusion criteria were used: (1) reviews or conferences or abstracts or letters to the editor; (2) duplicate study populations; (3) animal studies; (4) other cancer studies; (5) lack of RR or OR data; (6) other vitamin supplement studies.

Data extraction and quality evaluation

All included papers were examined and relevant data were retrieved independently by two researchers. Inclusion basic information included: name of first author, date of publication, country, type of study, vitamin type, cancer type, sample size of cases and controls, RR or OR and 95% CI for cancer, covariate correction. The disagreement between these two researchers was decided jointly by a third author. The quality of the included studies was assessed using the NOS scoring criteria (0 to 9 points), and those with a score > 6 were included in the meta-analysis.

Statistical Analysis

RRs or ORs with 95% confidence intervals were extracted from each study to assess the association of high retinol or carotenoid intake and low intake with cancer risk. The results generally combined in cohort studies are RR values, and the results generally combined in case-control studies are OR values. In order to better calculate and combine the results of studies, the difference between the two is negligible, and all the results are expressed as OR values. In addition, heterogeneity among studies was assessed by Q-test and I² statistic. Q test (P_Q) p value < 0.1 and I² > 50% indicated that there was significant statistical heterogeneity between studies, and the results were analyzed using a random-effects model. Otherwise, a fixed effects model was used. We used forest plots to present the meta-analysis results and used Begg's test as well as Begg's funnel plots to assess publication bias. In addition, by eliminating each study one by one, a sensitivity analysis was performed to check the stability of the results. Analyses were performed using Stata12.0 for Windows (Stata, College Station, TX, USA) and p < 0.05 was considered statistically significant.

3.1 Screening process for eligible literatures

The relevant literatures were searched in 3 main English databases according to the search strategy: PubMed (n = 235), Web of Science (n = 218), Embase (n = 173). After de-duplication (n = 376), the titles and abstracts of the remaining articles (n = 250) were examined and evaluated. 193 articles were rejected for purpose, article type (review, case study, or conference abstract), or irrelevant findings. 57 full-text articles were downloaded, of which 35 studies were rejected after initial analysis due to lack of important data or unsatisfactory quality of NOS scores. Finally, the meta-analysis comprised 22 papers that fully fulfilled the inclusion criteria and quality evaluation. Figure 1 depicts the search flow chart.

3.2 Characteristics of included research projects

Table 1 shows the main characteristics of the 22 included studies. Regarding dietary aspects, a total of five cohort studies were included, and 399,558 individuals were followed up for 5 to 15 years, eventually resulting in 6919 CRC patients. A total of 13 case-control studies involving 11,029 cases and 19,024 controls were included. With respect to serum, two cohort studies were included, with 32,428 participants and, ultimately, 272 patients with CRC. Two case-control studies involving 1073 cases and 1116 controls were included. Studies were published between 2000 and 2019. Eight studies were from European countries, eight from North American countries and six from Asian countries. The major nutrient species studied were carotenoids, lycopene, α-carotene, β-carotene, carotenoids, lutein/zeaxanthin, β-cryptoxanthin, and retinol. The included studies were adjusted for covariates, mainly including: gender, age, smoking, alcohol consumption, family history of CRC and physical activity. The NOS was scored from 6 to 8.

3.3 Association between dietary retinol and various carotenoids and Colorectal cancer risk

3.3.1 β-carotene

We combined a total of 20 sets of data from 11 studies. Comparing high and low intakes, dietary intake of β-carotene reduced the risk of CRC by 11% (OR = 0.89, 95% CI: 0.78-1.03 Figure2A)，but the association between the two was not significant( p_t =0.113), and due to significant heterogeneity (I² = 63.2%, p < 0.001), we used a random-effects model for pooled analysis. According to subgroup analysis by tumor type, it can be seen that there is no significant correlation between high intake and the risk of colon cancer (OR = 0.96, 95% CI: 0.84-1.09 Figure3A) and rectal cancer (OR = 1.06, 95% CI: 0.89-1.25 Figure3A). In the subgroup analysis by study type, both the cohort study (OR = 0.95, 95% CI: 0.85-1.07 Figure4A) and the case-control study (OR = 0.81, 95% CI: 0.63-1.05 Figure4A) showed a trend of β-carotene to reduce the risk of CRC, but none of them were significantly associated. Finally, according to gender subgroup analysis, β-carotene intake was not significantly associated with the risk of CRC in female (OR = 0.81, 95% CI: 0.97-1.19 Figure5A), but β-carotene intake was negatively associated with the risk of CRC in male (OR = 0.74, 95% CI: 0.55-0.99 Figure5A).

3.3.2 α-carotene

We combined a total of 10 sets of data from 5 studies. Comparing high and low intakes, dietary intake of α-carotene reduced the risk of CRC by 13% (OR = 0.87, 95% CI: 0.72 – 1.03 Figure2B), but the association between the two was not significant (p_t =0.110), and due to significant heterogeneity (I² = 55.3%, p =0.017), we used a random-effects model for pooled analysis. Subgroup analysis by tumor type showed that high intake was not significantly associated with the risk of colon cancer (OR = 0.96, 95% CI: 0.84-1.09 Figure3B) and rectal cancer (OR = 1.01, 95% CI: 0.76-1.35 Figure3B). In the subgroup analysis by study type, the cohort study (OR = 1.00, 95% CI: 0.86-1.16 Figure4B) showed no significant association between their intake and CRC, and the case-control study (OR = 0.69, 95% CI: 0.47-1.02 Figure4B) showed a trend, but no significant association, of their intake to reduce CRC. Finally, intake of α-carotene tended to reduce CRC in male (OR = 0.71, 95% CI: 0.42-1.22 Figure5B) and female (OR = 0.89, 95% CI: 0.61-1.30 Figure5B) according to gender subgroup analysis, but there was no significant association.

3.3.3 Lycopene

Seven studies were included to combine a total of 13 sets of data. High lycopene (OR = 0.93, 95% CI: 0.81 – 1.07 Figure2C) intake slightly, but not significantly (p_t =0.329), reduced CRC risk. Due to significant heterogeneity (I² = 65.6%, p =0.000), pooling was performed with a random-effects model. Subgroup analysis was performed according to tumor type, study type and gender. Colon cancer (OR = 0.97, 95% CI: 0.85 – 1.10 Figure3C), rectal cancer (OR = 1.11, 95% CI: 0.89 – 1.38 Figure3C), cohort study (OR = 1.04, 95% CI: 0.92 – 1.18 Figure4C), case-control study (OR = 0.82, 95% CI: 0.64 – 1.06 Figure4C), male (OR = 0.88, 95% CI: 0.65 – 1.18 Figure5C), female (OR = 0.96, 95% CI: 0.59 – 1.58 Figure5C). In subgroup analyses, case-control studies showed that lycopene intake was associated with a nonsignificant reduction in CRC risk. There was also a risk reduction effect in women, although it was not significant.

3.3.4 Lutein/Zeaxanthin

Six studies were included and a total of 12 sets of data were combined. There was no significant (p_t =0.508) association between high lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87 – 1.07 Figure2D) intake and CRC risk. No significant heterogeneity was found (I² = 10.6%, p =0.341), which was summarized using a fixed-effect model. Subgroup analysis was performed according to tumor type, study type and gender. Colon cancer (OR = 0.96, 95% CI: 0.84 – 1.09 Figure3D), rectal cancer (OR = 1.09, 95% CI: 0.86 – 1.39 Figure3D), cohort study (OR = 1.04, 95% CI: 0.90 – 1.21 Figure4D), case-control study (OR = 0.89, 95% CI: 0.76 – 1.04 Figure4D), male (OR = 0.89, 95% CI: 0.75 – 1.06 Figure5D), female (OR = 1.08, 95% CI: 0.88 – 1.32 Figure5D). In subgroup analysis, case-control studies showed that lutein/zeaxanthin intake was associated with a non-significant reduction in CRC risk. The risk reduction effect was also present in female, but was not significant.

3.3.5 β-cryptoxanthin

Eight studies were included and a total of 18 sets of data were combined. High β-cryptoxanthin (OR = 0.70, 95% CI: 0.54 – 0.90 Figure2E) intake was able to significantly (p_t =0.005) reduce CRC risk by 30%. High heterogeneity was found (I² = 85.4%, p =0.000), which was combined using the random-effects model. Subgroup analysis was performed according to tumor type, study type, and gender. Colon cancer (OR = 0.95, 95% CI: 0.85 – 1.06 Figure3E), rectal cancer (OR = 0.87, 95% CI: 0.71 – 1.06 Figure3E), cohort study (OR = 0.92, 95% CI: 0.83– 1.03 Figure4E), case-control study (OR = 0.36, 95% CI: 0.19 – 0.72 Figure4E), male (OR = 0.52, 95% CI: 0.30 – 0.89 Figure5E), female (OR = 0.65, 95% CI: 0.43 – 0.98 Figure5E). In subgroup analysis, β-cryptoxanthin intake significantly reduced the risk of CRC, both in male and female.

3.3.6 Total carotenoids

Eight studies were included and a total of 19 sets of data were combined. There was no significant (p_t =0.717) association between high carotenoids (OR = 0.97, 95% CI: 0.81-1.15 Figure2F) intake and CRC risk. There was significant heterogeneity (I² = 69.2%, p =0.000), which was combined using the random-effects model. Subgroup analysis was performed according to tumor type, study type and gender. Colon cancer (OR = 1.05, 95% CI: 0.92 – 1.20 Figure3F), rectal cancer (OR = 1.01, 95% CI: 0.81 – 1.26 Figure3F), cohort study (OR = 1.08, 95% CI: 0.94 – 1.25 Figure4F), case-control study (OR = 0.87, 95% CI: 0.70 – 1.08 Figure4F), male (OR = 1.08, 95% CI: 0.91 – 1.27 Figure5F), female (OR = 1.00, 95% CI: 0.80 – 1.25 Figure5F). No association was found between high carotenoids intake and the risk of CRC in any Subgroup group.

3.3.7 Retinol

Seven studies were included and a total of 15 sets of data were combined. There was no significant (p_t = 0.850) association between high retinol (OR = 0.99, 95% CI: 0.89 – 1.10 Figure2G) intake and CRC risk. There was no significant heterogeneity (I² = 34.5%, p =0.092), and fixed effect model was used for combination. Subgroup analysis was performed according to tumor type, study type and gender. Colon cancer (OR = 1.05, 95% CI: 0.86 – 1.27 Figure3G), rectal cancer (OR = 0.99, 95% CI: 0.89 – 1.11 Figure3G), cohort study (OR = 0.92, 95% CI: 0.60 – 1.43 Figure4G), case-control study (OR = 0.99, 95% CI: 0.89 – 1.11 Figure4G), male (OR = 1.30, 95% CI: 1.02 – 1.66 Figure5G), female (OR =0.79, 95% CI: 0.61 – 1.01 Figure6G). Retinol appeared to play a protective role in women, reducing CRC risk by 21%, although there was no significant association.

3.4 Association of serum retinol and carotenoid levels with Colorectal cancer risk

With regard to serum carotenoids, three studies were included and a total of 11 sets of data were combined. Serum total carotenoids (OR = 0.73, 95% CI: 0.58 – 0.93 Figure6A) were significantly (p_t = 0.01) negatively associated with CRC risk. The results showed significant heterogeneity (I² = 67.5%, p =0.001), which was combined using the random-effects model. The subgroup analysis was performed according to the type of nutrients. Serum α-carotene (OR = 0.61, 95% CI: 0.37 – 0.99 Figure6B) was significantly inversely associated with CRC risk. However, the serum content of β-carotene (OR = 0.83, 95% CI: 0.64 – 1.08 Figure6B), Lycopene (OR = 0.58, 95% CI: 0.22 – 1.54 Figure6B), and β-Cryptoxanthin (OR = 0.69, 95% CI: 0.28 – 1.69 Figure6B), although negatively correlated with CRC risk, was not significant. There was no correlation between serum Lutein/Zeaxanthin (OR = 0.99, 95% CI: 0.63 – 1.56 Figure6B) content and CRC risk.

With regard to serum retinol, three studies were included and a total of four sets of data were combined. High serum retinol (OR = 0.62, 95% CI: 0.26 – 1.49 Figure6C) was inversely associated with CRC risk, but the association was not significant (p_t = 0.284). The results showed significant heterogeneity (I² = 90.8%, p =0.000), and random effects model was used for combination. Subgroup analysis were also performed according to study type. Cohort studies (OR = 1.22, 95% CI: 0.80 – 1.86 Figure6D) showed no association between serum retinol and CRC risk, but case-control studies (OR = 0.29, 95% CI: 0.16 – 0.54 Figure6D) showed a significant inverse association between serum retinol and CRC risk.

3.5 Publication bias and Sensitivity analysis

Due to the reduction in serological studies included, bias testing and sensitivity analysis were not necessary. Therefore, we performed bias test and sensitivity analysis on the combined results of dietary retinol and carotenoids. We used Begg's test as well as Begg's funnel plot to assess publication bias. Begg's test results (Figure7): β-carotene (Pr > | z |=0.417), α-carotene (Pr > | z |=0.721), lycopene (Pr > | z |=0.464), β-Cryptoxanthin (Pr > | z |=0.075), Lutein/Zeaxanthin (Pr > | z |=0.304), Carotenoids (Pr > | z |=0.234), retinol (Pr > | z |=0.692). The results of bias test showed that all funnel plots were symmetrical and (Pr > | z | > 0.05), indicating that no significant publication bias was found in the combined results. Sensitivity analysis (Figure8) of the results was performed and the pooled OR varied in a limited range without significant change after removing each study, indicating that our results were stable. From this, it can be seen that the relevant conclusions we draw are stable and reliable.

Although vitamin A (retinol) and carotenoids are widely present in a variety of vegetables and fruits, many people still lack the intake of these nutrients. Therefore, the impact of retinol and carotenoid intake on CRC risk has important public health implications. We included a total of 22 studies that pooled clinical studies on dietary and serum retinol and carotenoids and CRC risk. Subgroup analysis was performed according to tumor type, study category and sex.

The results showed that dietary β-carotene intake was weakly but not significantly negatively correlated with CRC risk, but β-carotene could significantly lower CRC risk in the male population, showing a protective and preventive effect. The consumption of β-carotene lowered the risk of CRC, however the link was not statistically significant. A high lycopene consumption lowered CRC risk marginally but not dramatically. There was no link seen between high lutein/zeaxanthin consumption and CRC risk. β-cryptoxanthin intake dramatically lowered the risk of CRC in both men and women. There was no link found between high carotenoid consumption and CRC risk. High retinol consumption had no significant connection with CRC risk, although it appeared to be protective in women, lowering CRC risk by 21%. In summary, high β-cryptoxanthin intake can significantly reduce CRC risk, and β-carotene, α-carotene, and lycopene have the potential to lower the risk of CRC, but there is uncertainty and it must be continued to be explored. β-carotene has a preventive effect on CRC in men and retinol seems to have a preventive effect in women, and this difference has caused us to have new ideas for making adjustments to meals by gender.

Our study surprised us by the finding that a high intake of β-cryptoxanthin (OR = 0.70, 95% CI: 0.54–0.90) was able to significantly reduce CRC risk. β-cryptoxanthin is one of the six primary carotenoids. It is mostly present in citrus fruits, although it is also found in corn, peas, and other yellow animal products (16, 28). β-cryptoxanthin has been demonstrated in animal experiments to have preventative and inhibitory effects on a number of malignancies, including colon cancer (29), gastric cancer (30), lung cancer (31–33), bladder cancer (34),and liver cancer (35) through a variety of molecular mechanisms. It has been demonstrated that β-cryptoxanthin in combination with oxaliplatin dramatically increased the apoptosis of colon cancer cells in vitro and in vivo, indicating anti-tumor and therapeutic actions on CRC (29). From this point of view, although there are few studies on β-cryptoxanthin, it may have a role in preventing and inhibiting tumors in a variety of cancers, especially CRC. The conclusions about β-cryptoxanthin in this meta-analysis should be paid attention to, and strengthening the study of β-cryptoxanthin may bring fruitful results.

In addition to focusing on the risk of dietary retinol and carotenoids on CRC, we also focused on serological aspects of the study. A significant inverse association was found between serum carotenoid concentrations and CRC risk. Serum β-carotene was shown to have a substantial negative relationship with CRC risk. Other carotenoids, while adversely associated, were not significant. Case-control studies have found a substantial negative link between serum retinol and CRC risk, while cohort studies have found no significant relationship, hence the relationship between serum retinol and CRC remains unknown and must be confirmed by large prospective investigations. Most previous studies have focused on dietary carotenoids, but in recent years attention has gradually shifted to serum carotenoids, possibly due to the development of serum detection techniques and more stable and accurate quantitative assessment of serum. Serum carotenoids are widely studied, in addition to CRC (36, 37), but also associated with the risk of breast cancer(38), lung cancer(39), prostate cancer(40, 41)and hepatocellular carcinoma(42), which can be used as a key research direction in the future. If the relationship between serum carotenoids and various cancers can be clearly understood, routine admission examination can be performed in high-risk cancer population to preliminarily evaluate and screen related tumors, which has certain application prospects in clinical practice.

We will further explore the mechanisms underlying the prevention and suppression of CRC by carotenoids. β-carotene has been found in animal studies to have anti-colon cancer properties through modulating M2 macrophages and activated fibroblasts(43). By regulating K-ras, PKB, and beta-catenin, dietary lutein can decrease colon carcinogenesis caused by p-dimethylhydrazine in rats(44). Carotenoids isolated from Chlorella ellipsoidea and Chlorella vulgaris have also been shown in cell tests to have antiproliferative and anticancer effects on human colon cancer cells(45). B-carotene has been demonstrated to decrease colon cancer cell development by reducing COX-2 production and down-regulating colon cancer cell homeostasis(46). A growing number of experimental investigations have also proven the mechanism and significance of carotenoids in anti-colorectal cancer.

There have also been several earlier meta-analyses investigating the relationship between carotene and CRC. Mannisto et al performed a meta-analysis of cohort studies on dietary carotenoids and CRC risk in 2006, and discovered no link between any carotenoids and CRC risk(47). Conclusion may be caused by several limitations. On the one hand, we believe that the relevant studies it includes are somewhat old and not suitable for the dietary pattern of modern humans. On the other hand, the studies it included were Caucasian studies in Europe and North America with certain geographical limitations; At the time, communication technology was limited, which easily led to a loss due to follow-up bias. Wang et al. performed a meta-analysis of observational data on lycopene consumption and CRC risk in 2016(48). The data indicate that lycopene consumption is not related with an increased risk of CRC, which is consistent with our findings. In 2016, Panic et al performed a meta-analysis of dietary carotenoid consumption and CRC risk, which found no significant link between dietary carotenoid intake and CRC(49).The reason for the inconsistency with our findings is that on the one hand we updated and added several new studies, on the other hand our study was performed in strict accordance with the quality assessment rules and removed several unqualified studies, and his study included these low-quality articles, which may affect the results. Third, we also conducted a gender subgroup analysis that may derive the effect of gender differences, and his study did not consider gender differences. Our findings are not consistent with the above the meta-analyses, but our study is highly credible.

We found clear heterogeneity in the entire summary results for retinol and carotenoids and CRC risk. Heterogeneity is typical in meta-analysis, and determining the source of the heterogeneity is an important step. First, where the heterogeneity of the data was considerable, we utilized a random-effects model to combine effect sizes. Second, we conducted a subgroup analysis by tumor type, research type, and gender. Most studies' heterogeneity was greatly decreased after subgroup analysis. Third, we conducted a sensitivity analysis to exclude the one that had the biggest influence on the research outcomes, hence lowering heterogeneity. In addition, there may be many factors that can increase heterogeneity, such as differences in race, region, dietary structure, ideology, and degree of economic development. As a result, the conclusions drawn should be treated with caution.

Our meta-analysis provides a number of advantages. First, for the first time, we not only evaluated the association between dietary carotenoids and retinol and CRC risk, but also performed serological aspects. Furthermore, each of the six major groups of carotenoids was thoroughly examined. Second, because this study included a large number of cases and participants, more reliable estimations of the connection between retinol and carotenoid consumption and CRC risk may be obtained. Third, there was no evidence of significant publication bias in our meta-analysis. Fourth, we conducted a detailed subgroup analysis according to tumor type, study type, and gender. Fifth, the results of our included studies were all adjusted for covariates. Sixth, we included studies from the last 20 years, avoiding that old dietary patterns influence the accuracy of study conclusions.

Our study has several limitations. First, we only included English articles, which may cause selection bias. Second, there is a large heterogeneity in the findings, although the sources of heterogeneity have been explored. Third, study results were not analyzed by region and race. Fourth, the specific doses of retinol and carotenoids were not stated, and no dose-response meta-analysis was performed. Fifth, detection and transformation tools for retinol and carotenoids contained in ingested foods are not described. Sixth, although all results were adjusted for covariates, it is possible that there are other factors that affect the accuracy of the results.

Dietary β-carotene considerably decreased CRC risk in the male population, and dietary β-cryptoxanthin significantly reduced CRC risk. Alternatively, serum carotenoid concentrations were significantly inversely related to CRC risk. From this, it can be seen that carotenoids have some benefits in preventing CRC, especially β-carotene and β-cryptoxanthin. However, because of these limitations and the heterogeneity of this meta-analysis, large prospective studies with adequate sample size, well-controlled confounders, and long follow-up are warranted. In this process, the toxicity caused by high-dose retinol and carotenoids should be considered.

Acknowledgments

We would like to thank the researchers and study participants for their contributions.

Author Contributions

Xiaoyong Han and Rangyin Zhao conceived the study; Guangming Zhang and Yajun Jiao performed the literature search; Da Wang and Yongfeng Wang extracted the required data; Xiaoyong Han performed the statistical analyses; Xiaoyong Han and Rangyin Zhao wrote a draft; Hui Cai and Kehu Yang reviewed the paper. All authors viewed and gave permission to publish this manuscript.

Funding

This work was supported by grants from the Central to guide local scientific and Technological Development(ZYYDDFFZZJ-1), Gansu Provincial Youth Science and Technology Fund Program (21JR7RA642), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(21GSSYC-2), Gansu Provincial Science and Technology Fund Program (18JR3RA052), Lanzhou talent innovation and Entrepreneurship Project (2016-RC-56), Gansu Provincial Hospital project(2019-206), Gansu Provincial Hospital project(ZX-62000001-2021-302)..

Data Availability Statement

The data presented in this study are available in the inserted articles.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing financial interests.

Bray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer. 2021;127(16):3029-30.
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
Doubeni CA, Major JM, Laiyemo AO, Schootman M, Zauber AG, Hollenbeck AR, et al. Contribution of behavioral risk factors and obesity to socioeconomic differences in colorectal cancer incidence. Journal of the National Cancer Institute. 2012;104(18):1353-62.
Zhou J, Zheng R, Zhang S, Zeng H, Wang S, Chen R, et al. Colorectal cancer burden and trends: Comparison between China and major burden countries in the world. Chin J Cancer Res. 2021;33(1):1-10.
Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467-80.
Sharma S, Katoch V, Kumar S, Chatterjee S. Functional relationship of vegetable colors and bioactive compounds: Implications in human health. J Nutr Biochem. 2021;92:108615.
Negri E, La Vecchia C, Franceschi S, D'Avanzo B, Parazzini F. Vegetable and fruit consumption and cancer risk. Int J Cancer. 1991;48(3):350-4.
Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003;78(3 Suppl):559s-69s.
Li C, Imai M, Matsuura T, Hasegawa S, Yamasaki M, Takahashi N. Inhibitory Effects of Retinol Are Greater than Retinoic Acid on the Growth and Adhesion of Human Refractory Cancer Cells. Biol Pharm Bull. 2016;39(4):636-40.
Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of Vitamin A in the Immune System. J Clin Med. 2018;7(9).
Clagett-Dame M, Knutson D. Vitamin A in reproduction and development. Nutrients. 2011;3(4):385-428.
Dao DQ, Ngo TC, Thong NM, Nam PC. Is Vitamin A an Antioxidant or a Pro-oxidant? J Phys Chem B. 2017;121(40):9348-57.
Siddikuzzaman, Grace VM. Antioxidant potential of all-trans retinoic acid (ATRA) and enhanced activity of liposome encapsulated ATRA against inflammation and tumor-directed angiogenesis. Immunopharmacol Immunotoxicol. 2013;35(1):164-73.
Zhang X, Dai B, Zhang B, Wang Z. Vitamin A and risk of cervical cancer: a meta-analysis. Gynecol Oncol. 2012;124(2):366-73.
Maiani G, Castón MJ, Catasta G, Toti E, Cambrodón IG, Bysted A, et al. Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Mol Nutr Food Res. 2009;53 Suppl 2:S194-218.
Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and disease. Nutrients. 2014;6(2):466-88.
Tanaka T, Shnimizu M, Moriwaki H. Cancer chemoprevention by carotenoids. Molecules. 2012;17(3):3202-42.
Saini RK, Keum YS, Daglia M, Rengasamy KR. Dietary carotenoids in cancer chemoprevention and chemotherapy: A review of emerging evidence. Pharmacol Res. 2020;157:104830.
Bushue N, Wan YJ. Retinoid pathway and cancer therapeutics. Adv Drug Deliv Rev. 2010;62(13):1285-98.
Rowles JL, 3rd, Erdman JW, Jr. Carotenoids and their role in cancer prevention. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(11):158613.
Leenders M, Leufkens AM, Siersema PD, van Duijnhoven FJ, Vrieling A, Hulshof PJ, et al. Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2014;135(12):2930-9.
Murtaugh MA, Ma KN, Benson J, Curtin K, Caan B, Slattery ML. Antioxidants, carotenoids, and risk of rectal cancer. Am J Epidemiol. 2004;159(1):32-41.
Rosato V, Bosetti C, Levi F, Polesel J, Zucchetto A, Negri E, et al. Risk factors for young-onset colorectal cancer. Cancer Causes Control. 2013;24(2):335-41.
Shin A, Li H, Shu XO, Yang G, Gao YT, Zheng W. Dietary intake of calcium, fiber and other micronutrients in relation to colorectal cancer risk: Results from the Shanghai Women's Health Study. Int J Cancer. 2006;119(12):2938-42.
Park SY, Nomura AM, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN. Carotenoid intake and colorectal cancer risk: the multiethnic cohort study. J Epidemiol. 2009;19(2):63-71.
Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, Tjønneland A. Micronutrient intake and risk of colon and rectal cancer in a Danish cohort. Cancer Epidemiol. 2010;34(1):40-6.
Granado F, Olmedilla B, Blanco I, Rojas-Hidalgo E. Major fruit and vegetable contributors to the main serum carotenoids in the Spanish diet. European journal of clinical nutrition. 1996;50(4):246-50.
San Millán C, Soldevilla B, Martín P, Gil-Calderón B, Compte M, Pérez-Sacristán B, et al. β-Cryptoxanthin Synergistically Enhances the Antitumoral Activity of Oxaliplatin through ΔNP73 Negative Regulation in Colon Cancer. Clin Cancer Res. 2015;21(19):4398-409.
Gao M, Dang F, Deng C. β-Cryptoxanthin induced anti-proliferation and apoptosis by G0/G1 arrest and AMPK signal inactivation in gastric cancer. Eur J Pharmacol. 2019;859:172528.
Iskandar AR, Liu C, Smith DE, Hu KQ, Choi SW, Ausman LM, et al. β-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice. Cancer Prev Res (Phila). 2013;6(4):309-20.
Liu C, Bronson RT, Russell RM, Wang XD. β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets. Cancer Prev Res (Phila). 2011;4(8):1255-66.
Iskandar AR, Miao B, Li X, Hu KQ, Liu C, Wang XD. β-Cryptoxanthin Reduced Lung Tumor Multiplicity and Inhibited Lung Cancer Cell Motility by Downregulating Nicotinic Acetylcholine Receptor α7 Signaling. Cancer Prev Res (Phila). 2016;9(11):875-86.
Miyazawa K, Miyamoto S, Suzuki R, Yasui Y, Ikeda R, Kohno H, et al. Dietary beta-cryptoxanthin inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Oncol Rep. 2007;17(2):297-304.
Lim JY, Liu C, Hu KQ, Smith DE, Wu D, Lamon-Fava S, et al. Xanthophyll β-Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet-Promoted Hepatocellular Carcinoma Progression in Mice. Mol Nutr Food Res. 2020;64(3):e1900949.
Huang J, Lu MS, Fang YJ, Xu M, Huang WQ, Pan ZZ, et al. Serum carotenoids and colorectal cancer risk: A case-control study in Guangdong, China. Mol Nutr Food Res. 2017;61(10).
Guertin KA, Li XS, Graubard BI, Albanes D, Weinstein SJ, Goedert JJ, et al. Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study. Cancer Epidemiol Biomarkers Prev. 2017;26(6):945-52.
Yan B, Lu MS, Wang L, Mo XF, Luo WP, Du YF, et al. Specific serum carotenoids are inversely associated with breast cancer risk among Chinese women: a case-control study. Br J Nutr. 2016;115(1):129-37.
Asbaghi S, Saedisomeolia A, Hosseini M, Honarvar NM, Khosravi A, Azargashb E. Dietary Intake and Serum Level of Carotenoids in Lung Cancer Patients: A Case-Control Study. Nutr Cancer. 2015;67(6):893-8.
Kristal AR, Till C, Platz EA, Song X, King IB, Neuhouser ML, et al. Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev. 2011;20(4):638-46.
Beilby J, Ambrosini GL, Rossi E, de Klerk NH, Musk AW. Serum levels of folate, lycopene, β-carotene, retinol and vitamin E and prostate cancer risk. European journal of clinical nutrition. 2010;64(10):1235-8.
Lai GY, Weinstein SJ, Albanes D, Taylor PR, Virtamo J, McGlynn KA, et al. Association of serum α-tocopherol, β-carotene, and retinol with liver cancer incidence and chronic liver disease mortality. Br J Cancer. 2014;111(11):2163-71.
Lee NY, Kim Y, Kim YS, Shin JH, Rubin LP, Kim Y. β-Carotene exerts anti-colon cancer effects by regulating M2 macrophages and activated fibroblasts. J Nutr Biochem. 2020;82:108402.
Reynoso-Camacho R, González-Jasso E, Ferriz-Martínez R, Villalón-Corona B, Loarca-Piña GF, Salgado LM, et al. Dietary supplementation of lutein reduces colon carcinogenesis in DMH-treated rats by modulating K-ras, PKB, and β-catenin proteins. Nutr Cancer. 2011;63(1):39-45.
Cha KH, Koo SY, Lee DU. Antiproliferative effects of carotenoids extracted from Chlorella ellipsoidea and Chlorella vulgaris on human colon cancer cells. J Agric Food Chem. 2008;56(22):10521-6.
Palozza P, Serini S, Maggiano N, Tringali G, Navarra P, Ranelletti FO, et al. beta-Carotene downregulates the steady-state and heregulin-alpha-induced COX-2 pathways in colon cancer cells. J Nutr. 2005;135(1):129-36.
Männistö S, Yaun SS, Hunter DJ, Spiegelman D, Adami HO, Albanes D, et al. Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies. Am J Epidemiol. 2007;165(3):246-55.
Wang X, Yang HH, Liu Y, Zhou Q, Chen ZH. Lycopene Consumption and Risk of Colorectal Cancer: A Meta-Analysis of Observational Studies. Nutr Cancer. 2016;68(7):1083-96.
Panic N, Nedovic D, Pastorino R, Boccia S, Leoncini E. Carotenoid intake from natural sources and colorectal cancer: a systematic review and meta-analysis of epidemiological studies. Eur J Cancer Prev. 2017;26(1):27-37.
Williams CD, Satia JA, Adair LS, Stevens J, Galanko J, Keku TO, et al. Antioxidant and DNA methylation-related nutrients and risk of distal colorectal cancer. Cancer Causes Control. 2010;21(8):1171-81.
Slattery ML, Benson J, Curtin K, Ma KN, Schaeffer D, Potter JD. Carotenoids and colon cancer. Am J Clin Nutr. 2000;71(2):575-82.
Terry P, Jain M, Miller AB, Howe GR, Rohan TE. Dietary carotenoid intake and colorectal cancer risk. Nutr Cancer. 2002;42(2):167-72.
Nkondjock A, Ghadirian P. Dietary carotenoids and risk of colon cancer: case-control study. Int J Cancer. 2004;110(1):110-6.
Wang Z, Joshi AM, Ohnaka K, Morita M, Toyomura K, Kono S, et al. Dietary intakes of retinol, carotenes, vitamin C, and vitamin E and colorectal cancer risk: the Fukuoka colorectal cancer study. Nutr Cancer. 2012;64(6):798-805.
Negri E, La Vecchia C, Franceschi S. Relations between vegetable, fruit and micronutrient intake. Implications for odds ratios in a case-control study. European journal of clinical nutrition. 2002;56(2):166-70.
Levi F, Pasche C, Lucchini F, La Vecchia C. Selected micronutrients and colorectal cancer. a case-control study from the canton of Vaud, Switzerland. Eur J Cancer. 2000;36(16):2115-9.
Lu MS, Fang YJ, Chen YM, Luo WP, Pan ZZ, Zhong X, et al. Higher intake of carotenoid is associated with a lower risk of colorectal cancer in Chinese adults: a case-control study. Eur J Nutr. 2015;54(4):619-28.
Paiva I, Amaral T, Barros H. Influence of individually estimated portion size on the assessment of nutritional risk in colorectal cancer in Portugal. J Hum Nutr Diet. 2004;17(6):529-36.
Key TJ, Appleby PN, Masset G, Brunner EJ, Cade JE, Greenwood DC, et al. Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium. Int J Cancer. 2012;131(3):E320-5.
Cook NR, Le IM, Manson JE, Buring JE, Hennekens CH. Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States). Cancer Causes Control. 2000;11(7):617-26.
Wakai K, Hirose K, Matsuo K, Ito H, Kuriki K, Suzuki T, et al. Dietary risk factors for colon and rectal cancers: a comparative case-control study. J Epidemiol. 2006;16(3):125-35.
Kabat GC, Kim MY, Sarto GE, Shikany JM, Rohan TE. Repeated measurements of serum carotenoid, retinol and tocopherol levels in relation to colorectal cancer risk in the Women's Health Initiative. European journal of clinical nutrition. 2012;66(5):549-54.
Luo H, Fang YJ, Lu MS, Pan ZZ, Huang J, Chen YM, et al. Dietary and serum vitamins A and E and colorectal cancer risk in Chinese population: a case-control study. Eur J Cancer Prev. 2019;28(4):268-77.
Malila N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L. Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. European journal of clinical nutrition. 2002;56(7):615-21.

Table 1

Characteristics of included studies.

Author Year Country	type of Cancer	type of study	sample size	Diet/ Serum	Nutrient Type	adjustment for covariates.	NOS score
Roswall(27) 2010 Denmark	Colon and rectal cancer	Cohort study	56332/748	Diet	β -carotene	Education, alcohol consumption, consumption of red and processed meat, smoking status	7
Maureen(23) 2004 USA	rectal cancer	Case-control study	952/1205	Diet	Lycopene, β -carotene，Lutein	Age, body mass index, physical activity, energy intake, dietary fiber, dietary calcium, and smoking status	7
Dawn(50) 2010 USA	Colorectal Cancer	Case-control study	945/959	Diet	β -carotene	Age, gender, education, smoking status, BMI, physical activity, family history, history of alcohol use	6
Park(26) 2009 USA	Colon and rectal cancer	Cohort study	191004/2378	Diet	Lycopene, α-carotene, β-carotene, Carotenoids，β-cryptoxanthin，Lutein	Gender, age, family history of colorectal cancer, history of intestinal polyps, number of pack-years smoked, body mass index	8
Slattery(51) 2000 USA	Colon cancer	Case-control study	1993/2410	Diet	Lycopene, α-carotene, β-carotene，β-cryptoxanthin，Lutein，Zeaxanthin	Age, gender, smoking, alcohol consumption, BMI and long term strenuous physical activity	7
Leenders(22) 2014 Europe	Colon and rectal cancer	Case-control study	1399/1399	Diet	Lycopene, α-carotene, β-carotene, Carotenoids, Retinol	Smoking, alcohol consumption, BMI, physical activity, consumption level	7
Terry(52) 2015 Canada	Colon and rectal cancer	Cohort study	56837/5681	Diet	Lycopene, α-carotene, β-carotene, Carotenoids	Smoking status, relative body mass (body mass index), total fat intake, energy, alcohol, and folic acid, or menopausal status	7
Andre(53) 2004 Canada	Colon cancer	Case-control study	402/688	Diet	Lycopene, α-carotene, β-carotene, Carotenoids，Lutein/ Zeaxanthin，β-Cryptoxanthin	Age, history of CC in first-degree relatives, marital status, gender, physical activity, fiber and folate consumption, and total energy intake	7
Wang(54) 2014 Japan	Colon and rectal cancer	Case-control study	816/815	Diet	Lycopene, Carotenoids	Age, residence, family history of colorectal cancer, smoking, alcohol consumption, BMI, type of work, physical activity	6
Negri(55) 2002 Italy	Colorectal Cancer	Case-control study	1953/4154	Diet	Lycopene, Carotenoids, Retinol	Sociodemographic characteristics, smoking, physical activity, anthropometric measurements at different ages, family history of cancer	7
Levi(56) 2000 Switzerland	Colorectal Cancer	Case-control study	223/491	Diet	Carotenoids, Retinol	Age, sex, education, smoking, alcohol, body mass index, physical activity, and total energy and fiber intake	7
Lu(57) 2015 China	Colorectal Cancer	Case-control study	845/845	Diet	Lycopene, α-carotene, β-carotene, Carotenoids，Lutein/Zeaxanthin，β-Cryptoxanthin	Education, marital status, occupation, income, family history of cancer, smoking status, passive smoking, alcohol consumption, occupational activities, family and leisure activities, BMI	7

Table 1

Con.

Author Year Country	type of Cancer	type of study	sample size	Diet/ Serum	Nutrient Type	adjustment for covariates.	NOS score
Paiva(58) 2004 Portugal	Colorectal Cancer	Case-control study	100/211	Diet	Carotenoids	Age, sex, marital status, work physical activity, family history of cancer, body mass index, fiber, carotene, vitamin C, and total energy	7
Valentina(24) 2013 Switzerland	Colorectal Cancer	Case-control study	329/1361	Diet	β-carotene	Age, gender, family history, alcohol use, education, physical activity	6
Timothy(59) 2012 UK	Colorectal Cancer	Case-control study	565/1951	Diet	β-carotene	Height, weight, energy intake, alcohol intake, dietary fiber, smoking, alcohol consumption, physical activity, education, social class	7
Nancy(60) 2000 USA	Colon and rectal cancer	Cohort study	22071/267	Diet	β-carotene	Age, education, marital status, occupation, income, family history of cancer, smoking status, passive smoking, alcohol consumption, occupational activity, BMI	7
Wakai(61) 2006 Japan	Colon and rectal cancer	Case-control study	507/2535	Diet	Carotenoids, Retinol	Sex, age, family history, smoking, alcohol use, physical activity, energy intake	7
Shin(25) 2006 China	Colon and rectal cancer	Cohort study	73314/283	Diet	Carotenoids, Retinol	Age, menopausal status, education, smoking, alcohol consumption, physical activity, family history of colorectal cancer, use of vitamin supplements, and total energy intake	8
Kabat(62) 2012 USA	Colorectal Cancer	Cohort study	5477/88	serum	Lycopene,α-carotene, β-carotene, Lutein+ Zeaxanthin，β-Cryptoxanthin, Retinol	Age, body mass index, waist circumference, alcohol intake, physical activity, family history of colorectal cancer, ethnicity	8
Huang(36) 2017 China	Colorectal Cancer	Case-control study	538/564	serum	Lycopene,α-carotene, β-carotene,，Lutein/ Zeaxanthin，β-Cryptoxanthin	Living conditions, educational level, occupation, income, study, alcohol consumption, family history of colorectal cancer, physical activity	7
Luo(63) 2019 China	Colon and rectal cancer	Case-control study	535/552	serum	Retinol	Age, sex, residence, educational level, marital status, income, family and leisure activities, passive smoking, alcohol consumption, adult height and BMI	6
Malila(64) 2002 Finland	Colorectal Cancer	Cohort study	26951/184	serum	Retinol, β-carotene	Age, body mass index (BMI), number of cigarettes smoked per day, occupational and leisure time physical activity, serum cholesterol concentration, alcohol intake	8

Table 2

Meta-results on intake of various nutrients and colorectal cancer risk

						Heterogeneity
Nutrient Type	studies(n)	OR	95%CI	P value	Model	Chi²	I²	P Value
β-carotene	20	0.89	0.78-1.03	0.113	random	51.61	63.2%	0.000
α-carotene	10	0.87	0.72-1.03	0.110	random	20.14	55.3%	0.017
Lycopene	13	0.93	0.81-1.07	0.329	random	34.83	65.6%	0.000
Lutein/Zeaxanthin	12	0.96	0.87-1.07	0.508	fix	12.31	10.6%	0.341
β-Cryptoxanthin	18	0.70	0.54-0.90	0.005	random	116.71	85.4%	0.000
Carotenoids	19	0.97	0.81-1.15	0.717	random	58.44	69.2%	0.000
Retinol	15	0.99	0.89-1.10	0.850	fix	21.37	34.5%	0.092
Carotenoids (serum)	11	0.73	0.58-0.93	0.010	random	30.79	67.5%	0.001
Retinol (serum)	4	0.62	0.26-1.49	0.284	random	30.51	90.8%	0.000

No competing interests reported.

TableS1.xlsx
Supplementary Materials: Table S1: We uploaded the data sheets of the included studies in the attachment section.

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Association of retinol and carotenoids content in diet and serum with risk for Colorectal cancer: a meta-analysis

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Abstract

Figures

1 Introduction

2 Materials And Methods

Search strategy for literature

Inclusion and exclusion criteria

Data extraction and quality evaluation

Statistical Analysis

3 Results

3.1 Screening process for eligible literatures

3.2 Characteristics of included research projects

3.3 Association between dietary retinol and various carotenoids and Colorectal cancer risk

3.3.1 β-carotene

3.3.2 α-carotene

3.3.3 Lycopene

3.3.4 Lutein/Zeaxanthin

3.3.5 β-cryptoxanthin

3.3.6 Total carotenoids

3.3.7 Retinol

3.4 Association of serum retinol and carotenoid levels with Colorectal cancer risk

3.5 Publication bias and Sensitivity analysis

4 Discussion

5 Conclusion

Declarations

Acknowledgments

Author Contributions

Funding

Data Availability Statement

Ethics approval and consent to participate

Consent for publication

Competing interests

References

Tables

Competing Interests

Supplementary Files

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