|Year : 2015 | Volume
| Issue : 2 | Page : 459-463
Differences of polyunsaturated fatty acid in patients with colorectal cancer and healthy people
Siping Wang, Jie Xie, Hong Li, Kai Yang
Department of Special Service, Chinese PLA General Hospital, Beijing, China
|Date of Web Publication||7-Jul-2015|
Department of Special Service, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing - 100853
Source of Support: None, Conflict of Interest: None
Objective: This study aims to compare the difference of polyunsaturated fatty acid (PUFA) between patients with colorectal cancer and healthy people and analyze the effect of PUFA on colorectal cancer by testing serum of PUFA.
Materials and Methods: One hundred and fifty-six healthy people and 79 patients with colorectal cancer were randomly chosen in Beijing, China. PUFA level was measured in two groups. According to different stages, sizes, degree of differentiation, lymph node metastases from patients with colorectal cancer, we compared metabolize situation of PUFA.
Results: Total omega-6 PUFA level was higher in healthy people group than that in colorectal cancer group (25.77 ± 3.21 vs. 26.86 ± 1.65, P = 0.0125); moreover, arachidonic acid (AA) level was also higher in healthy people group than that in colorectal cancer group (5.02 ± 1.32 vs. 6.08 ± 1.26, P = 0.0344); total omega-3 PUFA level was lower in colorectal cancer group than that in healthy people group; furthermore, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was also lower in colorectal cancer group than that in healthy people group. AA and total omega-6 were significant differences between less than 5 cm of tumor size and more than 5 cm of tumor size (13.11 ± 2.91 vs. 14.44 ± 1.81, P < 0.05; 27.02 ± 4.54 vs. 28.76 ± 3.08, P < 0.05).
Conclusion: PUFA level was significant difference between healthy people and colorectal cancer patients in the Chinese population. Tumor size probably had influence on the metabolism of PUFA.
Keywords: Colorectal cancer, docosahexaenoic acid, eicosapentaenoic acid, polyunsaturated fatty acid
|How to cite this article:|
Wang S, Xie J, Li H, Yang K. Differences of polyunsaturated fatty acid in patients with colorectal cancer and healthy people. J Can Res Ther 2015;11:459-63
| > Introduction|| |
Colorectal cancer is one of the most common malignant tumor. Diet factor and nutritional disorder also play important roles in tumorigenesis and tumor development. Recently, polyunsaturated fatty acid (PUFA) is more and more paid attention by clinical researchers. ,, PUFAs are necessary fatty acids in our bodies, which classify two categories: Omega-3 PUFA that includes α-linolenic acid (ALA, C18:3), eicosapentaenoic acid (EPA, C20:5), and docosahexaenoic acid (DHA, C22:6), and omega-6PUFA that includes linoleic acid (LA, C18:2), arachidonoic acid (AA, C20:4), dihomoglinolenic acid (DGLA, C20:3), docosapentaenoic acid (DPA, C22:5). Each component of these two categories are usually converted under rate-limiting enzyme. , Some studies suggested that omega-3 PUFA and metabolites are benefit on prevention of cardiovascular and cerebrovascular diseases, inhibition of inflammation and tumor, but effects of omega-6 PUFA are totally reversed. ,,,, We had investigated PUFA levels of 156 healthy crowd  and found that people's omega-3 levels were lower than international normal levels, but omega-6 levels were high than international normal levels. This indicated that Chinese had disorder of fatty acid nutrition. Here, we compared and analyzed differences of PUFA level between 79 patients with colorectal cancer and healthy people.
| > Materials and Methods|| |
Seventy-nine patients (42 males, 37 females, and 24-75 years old) with colorectal cancer were chosen randomly to perform prevalence study from 2013 to 2013 in our hospital. Then, we randomly chose 253 healthy people through physical examinations from January 2011 to May 2012 in *** Hospital, which included 102 males and 54 females, aged from 27 to 77 years. This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of *** Hospital. Written informed consent was obtained from all participants.
Two milliliter intravenous blood sample of each patient was extracted in the morning pre-operatavely for the determination after the anticoagulation. The determination method of fatty acid composition was referred to the international standards:  (1) Fatty acid extraction: The centrifuged red blood cell (RBC) (<50 μl) was placed in a mortar, then added the liquid nitrogen for the rapid homogenization. Then, the thoroughly homogenized RBC was transferred into the methylated glass tube (CNW 18-700 transparent threaded autosampler vial, 15 ml), and 1 ml n-hexane and 1 ml 14% boron trifluoride methanol reagent were added. After exhausted O 2 with N 2 , the methylated glass tube was sealed, the mixture was then heated to 100°C and continued for 1 h. After the tube cooled to room temperature, 1 ml water was added in. The methyl ester was then extracted in upper phase of n-hexane. Then, the sample was centrifuged at 1500 r/min for 1 min (with the centrifugal radius as 20 cm), the upper hexane layer was then shifted into a 1.5 ml vial (10-09-1196 Pupeng Technology) and blew dry with nitrogen. Moreover, 200 μl n-hexane was used to redissolve the dried sample, which was then shifted into a trace tube (06-09-0865 0.1 ml Pupeng Technology), and sealed after N 2 replaced O 2 . In this study, n-hexane and 14% boron trifluoride methanol reagents were purchased from Beijing Zebio Technology CO., Ltd. (2) Gas chromatographic analysis: The sealed vial was placed into a gas chromatograph analyzer (GC-2010 Plus ***, Japan) for the sample analysis. The target fatty acids were LA (C18: 2), LA (C18: 3), AA (C20: 4), DGLA (C20: 3), EPA (C20: 5), DPA (C22: 5), and DHA (C22: 6), etc., The level of each fatty acid composition was represented by the area ratio of the corresponding peak area to the total fatty acids (%).
Statistical analysis was performed by Statistical Package for the Social Sciences (SPSS) 13.3 software and all results were represented as mean ± standard deviation (SD), and calculated omega-3 index, total omega-3, and total omega-6 levels. Rank sum test and t-test were both used to analyze results, the frequency data were performed the Chi-square test, and P < 0.05 was considered as significant statistical difference.
| > Results|| |
Cases of healthy people were 156, including 102 males and 54 females and mean ages were 48.42 ± 9.2, cases of patients with colorectal cancer were 79, including 42 males and 37 females and mean ages were 49 ± 8.56. Ages and sex were both no significant difference between two groups; moreover, we tested some basic physical signs, such as smoking history, body mass index (BMI), blood pressure (BP), total cholesterol (TC), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL); finally, we found that all were no significant difference between two groups.
Colorectal cancer that all patients suffered from belonged to adenocarcinoma, according to TNM staging, stage I-IV were included 35, 35, 44, 44, respectively. Moreover, 40 cases had lymph node metastasis, 39 cases were low differentiation (grade III, poorly differentiated), 40 high differentiation (grade I and II, well-differentiated and moderately differentiated), and tumor sizes of 41 cases were less than 5 cm [Table 1].
PUFAs mainly included LA, DGLA, AA, ALA, EPA, and DHA, omega-3 index represented ratio of omega-3 in total PUFA. All components were tested whether their results were normal distribution and then results belonging to normal distribution were tested by t-test or results were tested by rank sum test. Our results showed that DGLA, AA, and total omega-6 were all significant differences between healthy group and colorectal cancer group; in addition, ALA, EPA, DHA, total omega-3, and omega-3 index were also significant differences between two groups [Table 2].
There was no significant statistical difference in the major PUFA content among different colorectal cancer groups, such as gender, age, tumor sites (rectum or colon), TNM staging, tumor differentiation and lymph node metastasis. While AA of omega-6 series and DHA of omega-3 series, when the tumors were more than and/or equal to 5cm and less than 5cm, exhibited significant difference (P > 0.05), and the omega-3 index also exhibited significant statistical difference (P> 0.05) [Table 3] and [Table 4].
|Table 3: Comparisons of PUFA in TNM staging, tumor differentiation, tumor size, lymph node metastasis|
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|Table 4: Comparisons of PUFA in TNM staging, tumor differentiation, tumor size, lymph node metastasis (continues)|
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| > Discussion|| |
As we know, essential fatty acids must be obtained from food, and economic condition and eating habits decide people's fatty acids levels. In our studies, we reported that many healthy people have nutritional disorder of fatty acids, which presented a lack of omega-3 PUFA, low index omega-3, and disorder of omega-6/omega-3 in our country.  But there are few reports about how PUFA levels are in patients with colorectal cancer. Therefore, we analyzed 79 colorectal cancer patients and observed their PUFA levels; according to our results, we found that there was significant difference between colorectal cancer patients and healthy people. Our study showed that total omega-6 level and AA level were both lower in patients with colorectal cancer than that in healthy people. There results could be explained, LA is a PUFA used in the biosynthesis of AA and is abundant in many vegetable oils. The first step in the metabolism of LA is performed by omega-6 desaturase, which converts LA into gamma-linolenic acid (GLA) and then GLA is converted to DGLA, which in turn is converted to AA. AA is an important inflammatory mediator and is produced a series of cytokines that cause proliferation of enterocytes, such as TAX2, PGE2, PGI2, and LTB4 by COX- 2 and LOX. ,, In our country, healthy people have higher omega-6 PUFA and patients with colorectal cancer have lower omega-6 PUFA. May be omega-6 is lost in patients. Our colleagues have reported that total omega-6 PUFA and LA levels were lower in colorectal cancer specimens than those in normal tissues,  which indicated that omega-6 PUFA was consumed in the process of development of tumorigeness and excessive cytokines were generated to change internal microenvironment to promote tumorigeness; thus, omega-6 PUFA, especially AA was considered as an important fatty acids that cells became malignant. Lack of omega-3 is a common phenomenon in present, especially for colorectal cancer patients, whose omega-3 index was 3.84 ± 1.33%. ,, Our results showed that total omega-3 and omega-3 index were both lower in colorectal cancer patients group than that in healthy people group (5.02 ± 1.32 vs. 6.08 ± 1.26, P = 0.0344; 3.84 ± 1.33 vs. 4.25 ± 1.16, P = 0.0268); furthermore, EPA and DHA were both lower in colorectal cancer patients group than that in healthy people (0.31 ± 0.27 vs. 0.39 ± 0.24, P = 0.0039; 3.53 ± 1.22 vs. 3.85 ± 1.00, P = 0.0448). These results further suggested that omega-3 was lack in colorectal cancer patients. , Maybe it is closely correlation with diet structure in society. Therefore, it is necessary to eat deep-sea fish that is abundant in omega-3 or related products contained omega-3. ,,
Recently, there is considerable support from preclinical studies that individual omega-3 PUFAs, or fish oil mixtures, have chemopreventative efficacy against colorectal cancer; Cockbain AJ and his colleague  have demonstrated that oral EPA treatment leads to incorporation of EPA into colorectal cancer tissue, is associated with possible reduced tumor vascularity, and has systemic anti-inflammatory activity. Remarkably, limited preoperative EPA exposure may prolong overall survival (OS) and disease free survival (DFS). Our results indicated that EPA was lower in colorectal cancer patients group than that in healthy people.
Why was low omega-3 level related to colorectal cancer? EPA is a major component of omega-3 and replaces AA as substrate of COX-2 to produce PGE3. Some studies have demonstrated that PGE2 promoted formation of colorectal cancer and inhibited proliferation of tumor cells and cancer cell liver metastasis. ,, Moreover, some reports found that EPA could reduce crypt cell proliferation and increase apoptosis in normal colonic mucosa. , We concluded that omega-3 PUFA possibly played anti-tumor role through three ways as follows: , Regulating the COX activity, changing liquidity of cell membranes and receptor function of cell membranes, and increasing cell antioxidant ability.
Here, we analyzed whether some factors had influenced on PUFA to patients with colorectal cancer, such as sex, age, part, TNM stage, differentiation, and lymph node metastases. Our results showed that there was no significant difference among their factors, except that AA, omega-5, total omega-3, and omega-3 were obvious difference between tumor size less than 5 cm and more than 5 cm (13.11 ± 2.91 vs. 14.44 ± 1.81, P> 0.05; 27.02 ± 4.54 vs. 28.76 ± 3.08, P> 0.05; 4.69 ± 1.43 vs. 5.57 ± 2.59, P> 0.05; 3.52 ± 1.39 vs. 4.20 ± 1.22, P> 0.05). These results suggested that tumor size was probably related to PUFA consumption.  However, few cases were studied, and we should study more research to prove them.
In conclusion, our results indicated that omega-6 and omega-3 levels were lower in colorectal cancer patients than those in healthy people in Beijing, China, and tumor size probably affected fatty acid metabolism. Thus, we must improve structure of diet nutrition positively and replenish omega-3 PUFA intake and reduce omega-6 PUFA intake so as to prevent from colorectal cancer.
| > Acknowledgements|| |
Thia study was supported by Grants from development fund of capital clinical application (Z101102050210004)
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[Table 1], [Table 2], [Table 3], [Table 4]