|
1
|
Vo HVT, Kim N, Lee HJ. Vitamin Bs as Potent Anticancer Agents through MMP-2/9 Regulation. FRONT BIOSCI-LANDMRK 2025; 30:24072. [PMID: 39862072 DOI: 10.31083/fbl24072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 08/17/2024] [Accepted: 08/28/2024] [Indexed: 01/27/2025]
Abstract
In recent years, the role of coenzymes, particularly those from the vitamin B group in modulating the activity of metalloenzymes has garnered significant attention in cancer treatment strategies. Metalloenzymes play pivotal roles in various cellular processes, including DNA repair, cell signaling, and metabolism, making them promising targets for cancer therapy. This review explores the complex interplay between coenzymes, specifically vitamin Bs, and metalloenzymes in cancer pathogenesis and treatment. Vitamins are an indispensable part of daily life, essential for optimal health and well-being. Beyond their recognized roles as essential nutrients, vitamins have increasingly garnered attention for their multifaceted functions within the machinery of cellular processes. In particular, vitamin Bs have emerged as a pivotal regulator within this intricate network, exerting profound effects on the functionality of metalloenzymes. Their ability to modulate metalloenzymes involved in crucial cellular pathways implicated in cancer progression presents a compelling avenue for therapeutic intervention. Key findings indicate that vitamin Bs can influence the activity and expression of metalloenzymes, thereby affecting processes such as DNA repair and cell signaling, which are critical in cancer development and progression. Understanding the mechanisms by which these coenzymes regulate metalloenzymes holds great promise for developing novel anticancer strategies. This review summarizes current knowledge on the interactions between vitamin Bs and metalloenzymes, highlighting their potential as anticancer agents and paving the way for innovative, cell-targeted cancer treatments.
Collapse
Affiliation(s)
- Ha Vy Thi Vo
- Department of Chemistry Education, Kongju National University, 32588 Gongju, Chungcheongnam-do, Republic of Korea
| | - Namdoo Kim
- Department of Chemistry, Kongju National University, 32588 Gongju, Chungcheongnam-do, Republic of Korea
| | - Hyuck Jin Lee
- Department of Chemistry Education, Kongju National University, 32588 Gongju, Chungcheongnam-do, Republic of Korea
| |
Collapse
|
|
2
|
Lee SM, Seol A, Cho HW, Min KJ, Lee S, Hong JH, Song JY, Lee JK, Lee NW. Optimal Dietary Intake of Riboflavin Associated with Lower Risk of Cervical Cancer in Korea: Korean National Health and Nutrition Examination Survey 2010-2021. Life (Basel) 2024; 14:529. [PMID: 38672799 PMCID: PMC11051093 DOI: 10.3390/life14040529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/17/2024] [Accepted: 04/19/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea. METHODS The data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day. RESULTS Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer. CONCLUSIONS The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.
Collapse
Affiliation(s)
- Seon-Mi Lee
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 73 Koreadae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; (S.-M.L.)
| | - Aeran Seol
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 73 Koreadae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; (S.-M.L.)
| | - Hyun-Woong Cho
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea
| | - Kyung-Jin Min
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan-si 15355, Gyeonggi-do, Republic of Korea
| | - Sanghoon Lee
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 73 Koreadae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; (S.-M.L.)
| | - Jin-Hwa Hong
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea
| | - Jae-Yun Song
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 73 Koreadae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; (S.-M.L.)
| | - Jae-Kwan Lee
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea
| | - Nak-Woo Lee
- Department of Obstetrics and Gynecology, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan-si 15355, Gyeonggi-do, Republic of Korea
| |
Collapse
|
|
3
|
Aslanov H, Bayramov B, Reissfelder C, Abdullayeva S, Mammadova Z, Aliyev F, Keese M, Hajibabazade J, Yagublu V. MTHFR Gene C677T Polymorphism (rs1801133) and Susceptibility to Colorectal Polyps in an Azerbaijani Population. J Clin Med 2023; 13:219. [PMID: 38202226 PMCID: PMC10779477 DOI: 10.3390/jcm13010219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 12/26/2023] [Accepted: 12/27/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Understanding the relationships between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, colorectal polyps, and CRC risk can aid in advancing personalized medicine approaches in CRC prevention. The aim of the current study is to identify the association of C677T polymorphism of the MTHFR gene with the risk of colorectal polyps in the Azerbaijani population. METHODS This study included 125 patients with colon polyps and 155 healthy individuals as a control group. DNA was extracted from venous blood samples obtained from patients and healthy individuals, and the results were analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis. RESULTS Wild-type, heterozygote, and homozygous mutant were revealed within 69 (55.2%), 49 (39.2%), and 7 (5.6%) patients and within 100 (64.5%), 45 (29%), and 10 (6.5%) healthy controls, respectively. However, no significant statistical associations were observed between CT and TT genotypes, dominant (CC vs. CT + TT) and recessive (CC + CT vs. TT) models, and the mutant T allele and disease risk. There were also no significant differences between patients and controls regarding age, sex, smoking and alcohol use. CONCLUSION Our research did not reveal any significant association between the MTHFR C677T polymorphism and susceptibility to colorectal polyps in the Azerbaijan population.
Collapse
Affiliation(s)
- Hazi Aslanov
- Department of Surgery, Scientific Center of Surgery after academician M.A.Topchubashov, Baku AZ1122, Azerbaijan;
| | - Bayram Bayramov
- Laboratory of Human Genetics, Genetic Resources Institute of Ministry of Science and Education, Baku AZ1106, Azerbaijan; (B.B.); (Z.M.)
- Department of Natural Sciences, Western Caspian University, Baku AZ1001, Azerbaijan
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany;
| | - Shams Abdullayeva
- Department of Neurology, Westpfalz-Klinikum, 67655 Kaiserslautern, Germany;
| | - Zeynab Mammadova
- Laboratory of Human Genetics, Genetic Resources Institute of Ministry of Science and Education, Baku AZ1106, Azerbaijan; (B.B.); (Z.M.)
| | - Fikrat Aliyev
- Department of Pathomorphology, Scientific Center of Surgery after academician M.A.Topchubashov, Baku AZ1122, Azerbaijan;
| | - Michael Keese
- Department of Vascular Surgery, Theresienkrankenhaus, 68165 Mannheim, Germany;
| | - Javahir Hajibabazade
- Carver College of Medicine, University of Iowa, Bowen Science Building, 51 Newton, Road, Iowa City, IA 52242-1009, USA
| | - Vugar Yagublu
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany;
| |
Collapse
|
|
4
|
Sørensen HM, Rochfort KD, Maye S, MacLeod G, Loscher C, Brabazon D, Freeland B. Bioactive Ingredients from Dairy-Based Lactic Acid Bacterial Fermentations for Functional Food Production and Their Health Effects. Nutrients 2023; 15:4754. [PMID: 38004148 PMCID: PMC10675170 DOI: 10.3390/nu15224754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/27/2023] [Accepted: 11/04/2023] [Indexed: 11/26/2023] Open
Abstract
Lactic acid bacteria are traditionally applied in a variety of fermented food products, and they have the ability to produce a wide range of bioactive ingredients during fermentation, including vitamins, bacteriocins, bioactive peptides, and bioactive compounds. The bioactivity and health benefits associated with these ingredients have garnered interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union, as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.
Collapse
Affiliation(s)
- Helena Mylise Sørensen
- School of Biotechnology, Dublin City University, D09 DX63 Dublin, Ireland; (C.L.); (B.F.)
- I-Form, Advanced Manufacturing Research Centre, Dublin City University, D09 DX63 Dublin, Ireland;
| | - Keith D. Rochfort
- School of Nursing, Psychotherapy and Community Health, Dublin City University, D09 DX63 Dublin, Ireland;
| | - Susan Maye
- Dairygold Co-Operative Society Limited, Clonmel Road, Co. Cork, P67 DD36 Mitchelstown, Ireland; (S.M.); (G.M.)
| | - George MacLeod
- Dairygold Co-Operative Society Limited, Clonmel Road, Co. Cork, P67 DD36 Mitchelstown, Ireland; (S.M.); (G.M.)
| | - Christine Loscher
- School of Biotechnology, Dublin City University, D09 DX63 Dublin, Ireland; (C.L.); (B.F.)
| | - Dermot Brabazon
- I-Form, Advanced Manufacturing Research Centre, Dublin City University, D09 DX63 Dublin, Ireland;
| | - Brian Freeland
- School of Biotechnology, Dublin City University, D09 DX63 Dublin, Ireland; (C.L.); (B.F.)
- I-Form, Advanced Manufacturing Research Centre, Dublin City University, D09 DX63 Dublin, Ireland;
| |
Collapse
|
|
5
|
Riboflavin Intake Inversely Associated with Cardiovascular-Disease Mortality and Interacting with Folate Intake: Findings from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Nutrients 2022; 14:nu14245345. [PMID: 36558504 PMCID: PMC9785396 DOI: 10.3390/nu14245345] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
The association between intakes of riboflavin and mortality has not been examined intensively in general populations. In this study, 10,480 adults in the 2005-2016 National Health and Nutrition Examination Survey (NHANES) were followed-up until 2019 for their vital status. Riboflavin and folate were assessed by two-day 24 h recall. The date and cause of death were obtained from the US Mortality Registry. The risks of all-cause mortality and cardiovascular disease (CVD) mortality were investigated using a Cox regression analysis. During a mean of 8.5 years follow-up, there were 1214 deaths registered (including 373 deaths from CVD and 302 from cancer). Compared to low level (quartile 1, Q1) of riboflavin intake, the hazard ratios (HRs) (95% confidence interval (CI)) for high level (quartile 4, Q4) were 0.53 (0.31-0.90) for CVD mortality and 0.62 (0.48-0.81) for all-cause mortality. The inverse association between riboflavin intake and CVD mortality was only significant among those with a high intake of folate (p for interaction 0.045). Those with a high folate intake (Q4) and low intake of riboflavin (Q1) had the highest risk of CVD mortality (HR 4.38, 95% CI 1.79-10.72), as compared with a high intake of both riboflavin and folate. In conclusion, riboflavin intake was inversely associated with all-cause mortality and CVD mortality, and the association was modified by folate intake.
Collapse
|
|
6
|
Screening and identification of potential prognostic biomarkers in bladder urothelial carcinoma: Evidence from bioinformatics analysis. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
|
|
7
|
The relationship between the index of nutritional quality and the risk of colorectal cancer and adenoma : a case-control study. Eur J Cancer Prev 2020; 29:222-228. [PMID: 32167962 DOI: 10.1097/cej.0000000000000550] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Colorectal cancer is one of the most common cancers in the world, whereas dietary factors are its most modifiable risk factors. The index of nutritional quality is considered as a general overview of the nutrient content of diet. The aim of this study is to determine the relationship between the index of nutritional quality and the risk of colorectal cancer and adenomas. METHODS Overall, 129 colorectal cancer and 130 colorectal adenoma cases and 240 healthy controls were studied in three major general hospitals in Tehran province, Iran. Index of nutritional quality scores were calculated based on information on the usual diet that was assessed by a valid and reliable Food Frequency Questionnaire. Multivariate logistic regression was used to estimate the relationship between the index of nutritional quality scores and the risk of colorectal cancer and adenoma. RESULTS After controlling for several confounding factors, the index of nutritional quality of calcium, vitamin C, riboflavin, folate and fiber were associated with decreased risk of colorectal cancer [ORcalcium: 0.21 (0.08-0.52), ORvitC: 0.16 (0.09-0.28), ORvitB2: 0.35 (0.18-0.65), ORfolate: 0.33 (0.16-0.65), ORfiber: 0.35 (0.21-0.58)]. Also, the inverse association were observed between risk of CRA and the index of nutritional quality of calcium, vitamin C, riboflavin, folate and fiber [OR calcium: 0.32 (0.14-0.74), ORvitC: 0.51 (0.34-0.73), ORvitB2: 0.48 (0.28-0.82), OR folate: 0.44 (0.23-0.81), OR fiber: 0.62 (0.42-0.92)]. CONCLUSION This study showed that individuals who have a healthier diet, high in calcium, vitamin C, riboflavin, folate and fiber and food groups like fruits, vegetables and whole-grain and less in sweets and red or process meats are at a lower risk of colorectal cancer and CRA than those with unhealthy and poor diet.
Collapse
|
|
8
|
Wang J, Wang Q, Luo Y, Gao T, Zhao Y, Pei R. In vitro selection of ssDNA aptamers that can specifically recognize and differentiate riboflavin and its derivative FAD. Talanta 2019; 204:424-430. [PMID: 31357315 DOI: 10.1016/j.talanta.2019.06.039] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/05/2019] [Accepted: 06/09/2019] [Indexed: 02/06/2023]
Abstract
It is very meaningful and useful to select specific aptamers with capacity to distinguish small structural analogues, but it is difficult to carry out by traditional affinity chromatography-SELEX (systematic evolution of ligands by exponential enrichment) based on immobilized target molecules. In this paper, as a proof of concept, we selected DNA aptamers that can specifically recognize and differentiate riboflavin and its derivative flavin adenine dinucleotide (FAD) by a modified method. Here, the random DNA library was indirectly immobilized on streptavidin functional agarose beads by hybridization with its biotinylated short complementary strand, and the specific affinity between aptamers and its target would induce the aptamers to release from beads. Binding specificity can be tailored by performing an additional negative SELEX with the structure analogue of target. After about 10 rounds of selection, 6 aptamers for riboflavin and 2 aptamers for FAD with good affinities were isolated, and their dissociation constants (Kds) were all at low micromolar level. Moreover, as expected, most of these aptamers show high affinity and excellent selectivity for target molecules, almost no binding to structure analogues and purines, indicating this simple method could be used to select specific aptamers to distinguish small molecular targets with similar structures.
Collapse
Affiliation(s)
- Jine Wang
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Qinglin Wang
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Yu Luo
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Tian Gao
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Yuewu Zhao
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Renjun Pei
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| |
Collapse
|
|
9
|
Genetic impact of methylenetetrahydrofolate reductase (MTHFR) polymorphism on the susceptibility to colorectal polyps: a meta-analysis. BMC MEDICAL GENETICS 2019; 20:94. [PMID: 31146742 PMCID: PMC6543585 DOI: 10.1186/s12881-019-0822-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 05/09/2019] [Indexed: 12/31/2022]
Abstract
Background There are several studies with inconsistent conclusions regarding the association between the rs1801133 and rs1801131 polymorphisms within the MTHFR (methylenetetrahydrofolate reductase) gene and colorectal polyp risk. This discrepancy led us to assess the genetic impact of the two polymorphisms on the susceptibility to colorectal polyps. Methods A meta-analysis was carried out for quantitative synthesis. According to the inclusion/exclusion criteria, we retrieved, screened and selected all published articles related to colorectal polyps and the MTHFR rs1801133 and rs1801131 polymorphisms. The P value of association test, RRs (risk ratios) and 95% CIs (confidence intervals) were mainly produced. Results A total of twenty-three case-control studies were included from twenty-two eligible articles. Pooling the results of both rs1801133 and rs1801131 polymorphisms in the overall population suggested a nonsignificant association between colorectal polyp cases and controls, in that all P values in the test of association were larger than 0.05. Nevertheless, pooling results in the “UK” subgroup of rs1801131, comprising five studies (1257 cases/1407 controls), indicated an elevated risk in colorectal polyp cases in comparison with controls, under the genetic models of CC vs. AA (P = 0.032, RR = 1.27, 95% CIs = 1.02, 1.57) and CC vs. AA+AC (P = 0.036, RR = 1.27, 95% CIs = 1.02, 1.60). Conclusion The C/C genotype of MTHFR rs1801131 is more likely to be a genetic risk factor for colorectal polyps in the UK region, although this finding should be verified with a larger sample size. Electronic supplementary material The online version of this article (10.1186/s12881-019-0822-y) contains supplementary material, which is available to authorized users.
Collapse
|
|
10
|
Zhao P, Hou J, Wu H, Zhong M. Analysis of genetic polymorphism of methylenetetrahydrofolate reductase in a large ethnic Hakka population in southern China. Medicine (Baltimore) 2018; 97:e13332. [PMID: 30557982 PMCID: PMC6320045 DOI: 10.1097/md.0000000000013332] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Methylenetetrahydrofolate reductase (MTHFR) catalyzes conversion of methylene tetrahydrofolate to methylte trahydrofolate. MTHFR C677T polymorphism has been regarded as a risk factor for various vascular diseases. Our study aimed to investigate the distribution frequencies of this polymorphism among Hakka population living in southern China. We retrospectively recruited 5102 unrelated Chinese Hakka subjects. MTHFR C677T polymorphism was tested using the polymerase chain reaction (PCR) and DNA sequencing. A total of 2358 males and 2744 females (aged from 10 years to 101 years) were included in this study. In total, 2835 (55.63%) subjects were homozygous for the C allele (CC), 1939 (38.00%) subjects were heterozygous (CT), and 325 (6.37%) subjects were homozygous for the T allele (TT). The allelic frequency of mutant T was 25.37% with 325 individual homozygous for this defective allele resulting in a frequency of about 6.37% for the TT genotype. According to the study results, the overall frequency of MTHFR C677T genotypes did not differ significantly among the gender and age groups. Our study showed the prevalence of MTHFR C677T polymorphism in a large ethnic Hakka population living in southern China. It would be important implications for the primary prevention of various vascular diseases.
Collapse
Affiliation(s)
- Pingsen Zhao
- Clinical Core Laboratory
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University
- Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases
- Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, P. R. China
| | - Jingyuan Hou
- Clinical Core Laboratory
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University
- Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases
- Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, P. R. China
| | - Hesen Wu
- Clinical Core Laboratory
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University
- Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases
- Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, P. R. China
| | - Miaocai Zhong
- Clinical Core Laboratory
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University
- Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases
- Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, P. R. China
| |
Collapse
|
|
11
|
Riboflavin in Human Health: A Review of Current Evidences. ADVANCES IN FOOD AND NUTRITION RESEARCH 2018; 83:57-81. [PMID: 29477226 DOI: 10.1016/bs.afnr.2017.11.002] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Riboflavin is a water-soluble vitamin, which was initially isolated from milk. There are two coenzyme forms of riboflavin, flavin mononucleotide and flavin adenine dinucleotide, in which riboflavin plays important roles in the enzymatic reactions. Riboflavin is found in a wide variety of animal and plant foods. Meat and dairy products are the major contributors of riboflavin dietary intake. In this chapter, the latest evidence on the relationship between riboflavin status and specific health risks will be reviewed. Also, some of the mechanisms by which riboflavin exerts its roles will be discussed. The evidence accrued suggests that riboflavin is an antioxidant nutrient which may prevent lipid peroxidation and reperfusion oxidative injury. Moreover, riboflavin deficiency may increase the risk of some cancers. Riboflavin may also exert a neuroprotective effects in some neurological disorders (e.g., Parkinson disease, migraine, and multiple sclerosis) through its role in some pathways that are hypothesized to be impaired in neurological disorders such as antioxidation, myelin formation, mitochondrial function, and iron metabolism.
Collapse
|
|
12
|
Moazzen S, Dolatkhah R, Tabrizi JS, Shaarbafi J, Alizadeh BZ, de Bock GH, Dastgiri S. Folic acid intake and folate status and colorectal cancer risk: A systematic review and meta-analysis. Clin Nutr 2017; 37:1926-1934. [PMID: 29132834 DOI: 10.1016/j.clnu.2017.10.010] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 10/12/2017] [Accepted: 10/14/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS To evaluate the controversies among the studies assessing the association between folic acid intake or folate status and colorectal cancer risk. METHODS PubMed, Cochrane library and references of related articles were searched from January 2000 to September 2016. Studies on folic acid intake or folate status and colorectal cancer or adenoma risk were included. Full text review was conducted for potentially eligible studies. Quality assessment was performed. Random-effects meta-analysis was used to estimate risk ratio and 95% Confidence Intervals. Analysis was conducted by Comprehensive Meta-Analysis software. RESULTS Folic acid supplement intake showed no significant effect on colorectal cancer risk in meta-analysis of randomized controlled trials, RR: 1.07 (95% CI: 0.86-1.43). The effect on risk was not significant in cohort studies either; RR = 0.96 (95% CI: 0.76-1.21). However, there was significant reduced colorectal cancer risk in total folate intake in cohort studies; 0.71 (95% CI: 0.59-0.86). Odds Ratio was also significantly reduced in case control studies; 0.77 (95% CI: 0.62-0.95). Nevertheless once folate status was measured as Red Blood Cell folate content, no significant effect on colorectal cancer risk was observed; 1.05 (95% CI: 0.85-1.30). CONCLUSION The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies. Findings of present study highlight the importance of individualized folic acid supplement intake given the fact that the beneficiary effects of long term folic acid supplementation is not confirmed.
Collapse
Affiliation(s)
- Sara Moazzen
- Health Service Management Research Center, Tabriz University of Medical Sciences, Tabriz 51666114731, Iran; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands.
| | - Roya Dolatkhah
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz 51666114731, Iran.
| | - Jafar Sadegh Tabrizi
- Health Service Management Research Center, Tabriz University of Medical Sciences, Tabriz 51666114731, Iran.
| | | | - Behrooz Z Alizadeh
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands; The Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz 51666114731, Iran.
| | - Geertruida H de Bock
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands.
| | - Saeed Dastgiri
- School of Medicine, Health Service Management Research Center, Tabriz University of Medical Sciences, Tabriz 51666114731, Iran.
| |
Collapse
|
|
13
|
Yoon YS, Jung S, Zhang X, Ogino S, Giovannucci EL, Cho E. Vitamin B2 intake and colorectal cancer risk; results from the Nurses' Health Study and the Health Professionals Follow-Up Study cohort. Int J Cancer 2017; 139:996-1008. [PMID: 27081929 DOI: 10.1002/ijc.30141] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Accepted: 04/01/2016] [Indexed: 12/30/2022]
Abstract
Vitamin B2 serves as a cofactor to enhance one-carbon metabolism, maintain mucous membranes, and has been implicated in lowering colorectal cancer (CRC) risk. However, few prospective studies have examined the association between vitamin B2 intake and CRC. In this study, we estimated the associations between vitamin B2 intake and CRC risk using the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) cohorts. Vitamin B2 intake was measured by a validated food frequency questionnaire every 4 years. Among 100,033 women in the NHS and 44,007 men in the HPFS we documented a total of 3,037 incident CRC cases (2,093 women and 944 men) during 24-26 years of follow-up until 2010. Intakes of total (from food and supplements), dietary (from food only), and supplemental vitamin B2 were inversely related to CRC risk in age-adjusted analysis in NHS. However, the association was attenuated and no longer statistically significant in multivariate analysis (p-trend ≥0.08). The pooled multivariate relative risks (95% confidence interval) comparing individuals in the extreme quintiles of intakes were 0.93 (0.81-1.06) for total vitamin B2, 0.89 (0.61-1.28) for dietary vitamin B2 and 0.94 (0.81-1.08) for supplemental vitamin B2. These associations of total vitamin B2 intake were similar for risk of CRC with varying lag-time periods (0-4, 4-8, 8-12 or 12-16 years), for risk of CRC subtypes by tumor location, and across strata of intake of folate or alcohol. Our prospective data do not support a beneficial role of vitamin B2 intake in lowering incidence of CRC.
Collapse
Affiliation(s)
- Yeong Sook Yoon
- Departments of Nutrition and Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Department of Family Medicine, Inje University Ilsan Paik Hospital, Goyang-Si, Gyeonggi-Do, Korea
| | - Seungyoun Jung
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine and Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA
| | - Shuji Ogino
- Departments of Nutrition and Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Department of Medicine and Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA.,Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Edward L Giovannucci
- Departments of Nutrition and Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Department of Medicine and Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA
| | - Eunyoung Cho
- Channing Division of Network Medicine, Department of Medicine and Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA.,Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, RI.,Department of Epidemiology, Brown University School of Public Health, Providence, RI
| |
Collapse
|
|
14
|
Masri OA, Chalhoub JM, Sharara AI. Role of vitamins in gastrointestinal diseases. World J Gastroenterol 2015; 21:5191-5209. [PMID: 25954093 PMCID: PMC4419060 DOI: 10.3748/wjg.v21.i17.5191] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 02/23/2015] [Accepted: 03/31/2015] [Indexed: 02/06/2023] Open
Abstract
A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available.
Collapse
|
|
15
|
Song M, Garrett WS, Chan AT. Nutrients, foods, and colorectal cancer prevention. Gastroenterology 2015; 148:1244-60.e16. [PMID: 25575572 PMCID: PMC4409470 DOI: 10.1053/j.gastro.2014.12.035] [Citation(s) in RCA: 456] [Impact Index Per Article: 45.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 11/26/2014] [Accepted: 12/01/2014] [Indexed: 02/07/2023]
Abstract
Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence.
Collapse
Affiliation(s)
- Mingyang Song
- Department of Nutrition, Harvard School of Public Health, Boston, MA,Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | - Wendy S. Garrett
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA,Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA,Department of Medicine, Harvard Medical School, Boston, MA,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
| | - Andrew T. Chan
- Department of Medicine, Harvard Medical School, Boston, MA,Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| |
Collapse
|
|
16
|
Xu L, Sun N, Zhou L, Chen X, Wang J, Wang Q, Wang K, Zhang J, Pei R. A label-free fluorescence assay for potassium ions using riboflavin as a G-quadruplex ligand. Analyst 2015; 140:3352-5. [DOI: 10.1039/c5an00242g] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A label-free fluorescence K+assay was developed using riboflavin, a new G-quadruplex ligand, and a G-quadruplex sequence (PW17).
Collapse
Affiliation(s)
- Lijun Xu
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Na Sun
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Lu Zhou
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Xing Chen
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Jine Wang
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Qinglin Wang
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Kewei Wang
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| | - Jianye Zhang
- School of Chemistry and Molecular Engineering
- Zhengzhou University
- Zhengzhou 450001
- P. R. China
| | - Renjun Pei
- Key Laboratory of Nano-Bio Interface
- Division of Nanobiomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
| |
Collapse
|
|
17
|
Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study. Cancer Causes Control 2014; 25:1119-29. [DOI: 10.1007/s10552-014-0412-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Accepted: 06/02/2014] [Indexed: 12/30/2022]
|
|
18
|
Chen FP, Lin CC, Chen TH, Tsai MC, Huang YC. Higher plasma homocysteine is associated with increased risk of developing colorectal polyps. Nutr Cancer 2013; 65:195-201. [PMID: 23441607 DOI: 10.1080/01635581.2013.756532] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Colorectal adenomas are considered to be precursors of colorectal cancer. B-vitamins (i.e., folate, vitamin B(6) and B(12)) are involved in homocysteine metabolism and play an important role as coenzymes in 1-carbon metabolism, which is thought to have a critical role in the progression of colorectal polyps. The purpose of this study was to examine the effects of B-vitamins and homocysteine on the risk of developing colorectal polyps. Forty-eight participants with colorectal polyps [29 adenomatous polyps (AP), 19 hyperplastic polyps (HP)], and 96 age- and sex-matched healthy controls were recruited. Fasting blood was drawn from each participant to measure hematological parameters, plasma pyridoxal 5'-phosphate (PLP), serum folate and vitamin B(12), and plasma homocysteine. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy controls. There was no significant difference in serum folate and vitamin B(12) and plasma PLP among the 3 groups. B-vitamins had no significant effect on the risk of colorectal polyps. However, participants with higher plasma homocysteine [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.13, 3.08) level exhibited significantly increased risk of colorectal polyps after adjusting for potential confounders. Plasma homocysteine was a strong predictor of the risk of colorectal polyps in participants with adequate B-vitamins status.
Collapse
Affiliation(s)
- Fang-Pei Chen
- School of Nutrition, Chung Shan Medical University, Taichung, Taiwan
| | | | | | | | | |
Collapse
|
|
19
|
Bassett JK, Severi G, Hodge AM, Baglietto L, Hopper JL, English DR, Giles GG. Dietary Intake of B Vitamins and Methionine and Colorectal Cancer Risk. Nutr Cancer 2013; 65:659-67. [DOI: 10.1080/01635581.2013.789114] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
20
|
Pabalan N, Jarjanazi H, Ozcelik H. A meta-analysis of the C1420T polymorphism in cytosolic serine hydroxymethyltransferase (SHMT1) among Caucasian colorectal cancer populations. Int J Colorectal Dis 2013; 28:925-32. [PMID: 23322534 DOI: 10.1007/s00384-013-1639-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/02/2013] [Indexed: 02/04/2023]
Abstract
PURPOSE Inconsistency of reported associations between the C1420T polymorphism in the cytosolic serine hydroxymethyltransferase (SHMT1) gene and colorectal cancer (CRC) prompted us to undertake a meta-analysis. METHODS We conducted searches of published literature in MEDLINE through PubMed up to April 2012. Individual data on 5,043 cases and 6,311 controls from 15 published case-control studies were evaluated. Meta-analyses were performed on the compiled dataset. RESULTS In the overall analysis, association was lacking between the C1420T polymorphism and CRC risk (odds ratio [OR] 0.96-1.04, p = 0.47-0.77), materially unchanged when reanalyzed without the Hardy-Weinberg equilibrium-deviating studies (OR 1.03-1.09, p = 0.22-0.55) or subjected to outlier treatment (OR 0.89-0.99, p = 0.10-0.8). In the ethnic subgroups, Europeans were susceptible (OR 1.11-1.17, p = 0.13-0.48) and Americans, slightly protected (OR 0.86-0.87, p = 0.49-0.61). The increased risk effects, however, became null following outlier treatment (OR 0.95-1.06). Test for interaction between decreased risk associations in the low-folate subgroup (OR 0.60-0.85, p = 0.009-0.03) with the susceptible effects in the high-folate category (OR 1.14-1.22, p = 0.19-0.32) was significant (p interaction = 0.004). CONCLUSIONS Overall summary estimates imply no associations but suggest geography-specific effects of the SHMT1 polymorphism that render Europeans susceptible, but not Americans. Folate status appears to show an inverse association of this polymorphism with CRC.
Collapse
Affiliation(s)
- Noel Pabalan
- Center for Research and Development, Angeles University Foundation, Angeles City 2009, Philippines
| | | | | |
Collapse
|
|
21
|
Aili A, Hasim A, Kelimu A, Guo X, Mamtimin B, Abudula A, Upur H. Association of the plasma and tissue riboflavin levels with C20orf54 expression in cervical lesions and its relationship to HPV16 infection. PLoS One 2013; 8:e79937. [PMID: 24260322 PMCID: PMC3832395 DOI: 10.1371/journal.pone.0079937] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Accepted: 09/26/2013] [Indexed: 12/14/2022] Open
Abstract
Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of which modulating riboflavin absorption, and it is also related with HPV infection.
Collapse
Affiliation(s)
- Aixingzi Aili
- Department of Gynecology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Ayshamgul Hasim
- Department of Pathology of the Medical University of Xinjiang, Urumqi, Xinjiang, China
| | - Alimujiang Kelimu
- Department of Neurosurgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Xia Guo
- Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Batur Mamtimin
- Pharmaceutical College of Xinjiang Medical University, Urumqi, Xinjiang, China
| | | | - Halmurat Upur
- Xinjiang Medical University, Urumqi, Xinjiang, China
- * E-mail:
| |
Collapse
|
|
22
|
Williams EA, Welfare M, Spiers A, Hill MH, Bal W, Gibney ER, Duckworth Y, Powers HJ, Mathers JC. Systemic folate status, rectal mucosal folate concentration and dietary intake in patients at differential risk of bowel cancer (The FAB2 Study). Eur J Nutr 2012; 52:1801-10. [PMID: 23271614 DOI: 10.1007/s00394-012-0483-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 12/09/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND/OBJECTIVES Folate has been strongly implicated in the aetiology of colorectal cancer. However, the relationship between dietary folate intake, rectal mucosal folate status and colorectal cancer risk is uncertain. The study aimed to estimate nutrient intakes and measure systemic folate status and rectal mucosal folate concentration in people at differential risk of developing colorectal cancer. METHODS Two hundred and twenty-eight individuals were recruited from gastroenterology clinics and subdivided into three patient groups: untreated colorectal cancer (n = 43), adenomatous polyps (n = 90) or normal bowel (n = 95). Biopsies from macroscopically normal rectal mucosa and blood were collected and used for the measurement of rectal mucosal 5-methyltetrahydrofolate (5-MeTHF) and systemic markers of folate status, respectively. Nutrient intake was estimated using a validated food frequency questionnaire. RESULTS Dietary intake variables, plasma 5-MeTHF and red cell folate and plasma homocysteine concentrations were similar in all three subject groups and 95% CI fell within normal range for each variable. Rectal mucosal 5-MeTHF concentration was higher in the normal mucosa of adenomatous polyp patients than in normal subjects (P = 0.055). Rectal mucosal 5-MeTHF was associated significantly with plasma folate (P < 0.001, r = 0.294), red cell folate (P = 0.014, r = 0.305), plasma homocysteine (P = 0.017, r = -0.163) and dietary folate intake (P = 0.036, r = 0.152). CONCLUSIONS This study demonstrates adequate folate status of patients attending gastroenterology clinics for the investigation of bowel symptoms, with no significant difference in dietary intakes or systemic folate status indices according to diagnosis. Rectal mucosal 5-MeTHF concentrations were elevated in adenomatous polyp patients, but failed to reach significance. Further studies are required to determine the biological significance of this observation.
Collapse
Affiliation(s)
- Elizabeth A Williams
- Human Nutrition Unit, Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Sheffield, Sheffield, S10 2RX, UK,
| | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Jung AY, Botma A, Lute C, Blom HJ, Ueland PM, Kvalheim G, Midttun Ø, Nagengast F, Steegenga W, Kampman E. Plasma B vitamins and LINE-1 DNA methylation in leukocytes of patients with a history of colorectal adenomas. Mol Nutr Food Res 2012; 57:698-708. [PMID: 23132835 DOI: 10.1002/mnfr.201200069] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 07/23/2012] [Accepted: 09/10/2012] [Indexed: 12/21/2022]
Abstract
SCOPE Low concentrations of folate, other B vitamins, and methionine are associated with colorectal cancer risk, possibly by changing DNA methylation patterns. Here, we examine whether plasma concentrations of B vitamins and methionine are associated with methylation of long interspersed nuclear element-1 (LINE-1) among those at high risk of colorectal cancer, i.e. patients with at least one histologically confirmed colorectal adenoma (CRA) in their life. METHODS AND RESULTS We used LINE-1 bisulfite pyrosequencing to measure global DNA methylation levels in leukocytes of 281 CRA patients. Multivariable linear regression was used to assess associations between plasma B vitamin concentrations and LINE-1 methylation levels. Plasma folate was inversely associated with LINE-1 methylation in CRA patients, while plasma methionine was positively associated with LINE-1 methylation. CONCLUSION This study does not provide evidence that in CRA patients, plasma folate concentrations are positively related to LINE-1 methylation in leukocytes but does suggest a direct association between plasma methionine and LINE-1 methylation in leukocytes.
Collapse
Affiliation(s)
- Audrey Y Jung
- Department of Epidemiology, Biostatistics, and HTA, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Kim J, Cho YA, Kim DH, Lee BH, Hwang DY, Jeong J, Lee HJ, Matsuo K, Tajima K, Ahn YO. Dietary intake of folate and alcohol, MTHFR C677T polymorphism, and colorectal cancer risk in Korea. Am J Clin Nutr 2012; 95:405-12. [PMID: 22218157 DOI: 10.3945/ajcn.111.020255] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The incidence of colorectal cancer (CRC) is increasing sharply in Korea, and evidence has suggested the role of dietary methyl supply and related polymorphisms on colorectal carcinogenesis. OBJECTIVE We investigated the association between folate and alcohol intake, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and CRC risk in Koreans. DESIGN A total of 787 cases and 656 controls were recruited from 2 university hospitals. Multiple logistic regression models were used to estimate ORs and corresponding 95% CIs. RESULTS MTHFR 677T homozygotes were at a lower risk of CRC (OR: 0.60; 95% CI: 0.46, 0.78 for TT compared with CC/CT). High folate intake was associated with reduced CRC risk (OR: 0.64; 95% CI: 0.49, 0.84 for high compared with low intake), and high alcohol consumption was associated with increased risk of CRC (OR: 1.76; 95% CI: 1.26, 2.46 for high compared with low intake). When data were stratified by the amount of dietary methyl (combined intake of folate and alcohol), those with low-methyl diets had higher risk of CRC (OR: 2.32; 95% CI: 1.18, 4.56) than did those with high-methyl diets among CC/CT carriers, whereas the amount of dietary methyl did not affect the CRC risk among carriers with the TT homozygous variant. This association was stronger in patients with colon cancer than in patients with rectal cancer. CONCLUSION We found that the effect of dietary methyl supply on colorectal carcinogenesis may differ according to MTHFR C677T genotype and the subsite of origin in a Korean population.
Collapse
Affiliation(s)
- Jeongseon Kim
- Cancer Epidemiology Branch, National Cancer Center, Goyang, South Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Ibiebele TI, Hughes MC, Pandeya N, Zhao Z, Montgomery G, Hayward N, Green AC, Whiteman DC, Webb PM. High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr 2011; 141:274-83. [PMID: 21178085 PMCID: PMC3021447 DOI: 10.3945/jn.110.131235] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.
Collapse
|
|
26
|
Levine AJ, Lee W, Figueiredo JC, Conti DV, Vandenberg DJ, Davis BD, Edlund CK, Henning SM, Heber D, Stern MC, Haile RW. Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study. Cancer Causes Control 2011; 22:541-52. [PMID: 21274745 PMCID: PMC3059778 DOI: 10.1007/s10552-011-9726-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2010] [Accepted: 01/06/2011] [Indexed: 12/22/2022]
Abstract
Background Folate-associated one-carbon metabolism (FOCM) is an important pathway in colorectal neoplasia risk but data on genetic variation in this pathway are largely limited to studies of single SNPs in selected genes. Methods We used a comprehensive tagSNP approach to study the association between genetic variation in 11 genes in the FOCM pathway and risk of incident distal colorectal adenomas in a sigmoidoscopy-based case–control study. We included 655 cases (one or more adenomas) and 695 controls (no adenomas) recruited from one of two Kaiser Permanente clinics between 1991 and 1995. We assessed a total of 159 tagSNPs selected using Haploview Tagger as well as selected non-synonymous SNPs. We used unconditional logistic regression to model the association between SNPs and risk of distal adenomas, assuming a log-additive model. Results Five SNPs in the SLC19A1 (RFC1) gene: rs1051266 (G80A), rs283895, rs2236484, rs12482346, and rs2838958 were associated with adenoma risk after correction for multiple testing (all corrected p values ≤0.043). The non-synonymous SLC19A1 SNP G80A interacted significantly with the MTHFRC677T genotype (interaction p value = 0.018). Conclusion Our data suggest that genetic variation in SLC19A1 may modify the risk of distal colorectal adenoma. Electronic supplementary material The online version of this article (doi:10.1007/s10552-011-9726-7) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- A Joan Levine
- Department of Preventive Medicine, Genetic Epidemiology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Abstract
Genetic factors clearly play a role in carcinogenesis, but migrant studies provide unequivocal evidence that environmental factors are critical in defining cancer risk. Therefore, one may expect that the lower availability of substrate for biochemical reactions leads to more genetic changes in enzyme function; for example, most studies have indicated the variant MTHFR genotype 677TT is related to biomarkers, such as homocysteine concentrations or global DNA methylation particularly in a low folate diet. The modification of a phenotype related to a genotype, particularly by dietary habits, could support the notion that some of inconsistencies in findings from molecular epidemiologic studies could be due to differences in the populations studied and unaccounted underlying characteristics mediating the relationship between genetic polymorphisms and the actual phenotypes. Given the evidence that diet can modify cancer risk, gene-diet interactions in cancer etiology would be anticipated. However, much of the evidence in this area comes from observational epidemiology, which limits the causal inference. Thus, the investigation of these interactions is essential to gain a full understanding of the impact of genetic variation on health outcomes. This report reviews current approaches to gene-diet interactions in epidemiological studies. Characteristics of gene and dietary factors are divided into four categories: one carbon metabolism-related gene polymorphisms and dietary factors including folate, vitamin B group and methionines; oxidative stress-related gene polymorphisms and antioxidant nutrients including vegetable and fruit intake; carcinogen-metabolizing gene polymorphisms and meat intake including heterocyclic amins and polycyclic aromatic hydrocarbon; and other gene-diet interactive effect on cancer.
Collapse
Affiliation(s)
- Sang-Ah Lee
- Department of Preventive Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
| |
Collapse
|
|
28
|
Wu X, Li D, Liu Z, Wan X, Wu Y, Jiang C, Qian Q. Vascular endothelial growth factor 1498C/T, 936C/T polymorphisms associated with increased risk of colorectal adenoma: a Chinese case-control study. Mol Biol Rep 2010; 38:1949-55. [PMID: 20857215 DOI: 10.1007/s11033-010-0316-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2010] [Accepted: 09/03/2010] [Indexed: 12/25/2022]
Abstract
Single nucleotide polymorphisms in vascular endothelial growth factor gene VEGF, 1498C/T and 936 C/T are associated with colorectal cancer. We sought to determine whether such genetic variability in VEGF contributes to susceptibility of colorectal adenoma (CRA), a presumably precancerous state of colorectal cancer. In this research, two aforementioned polymorphisms were investigated for CRA susceptibility in a Chinese case-control study. The epidemiological risk factors were collected through questionnaire. The plasma VEGF levels were measured via enzyme-linked immunosorbent assay (ELISA). The Taqman-Probe assay was used to determine genotypes in 224 CRA patients and 200 CRA-free controls. The clinicopathological data of each sample were collected for further correlation analysis. According to data analysis males, cigarette smokers, patients who carry metabolic syndrome or familial antecedent of adenomas were significantly associated with CRA risk. Plasma VEGF levels of CRA patients were higher than those of controls (P = 0.003). This difference is independent of genotypes. The carriers with 936CT and CT+TT had higher risk of CRA in comparison with controls (CT vs. CC, OR 2.00, 95% CI 1.23-3.25, P = 0.006; CT+TT vs. CC, OR 2.04, 95% CI 1.28-3.26, P = 0.003). 936-T allele was associated with increased risk of CRA (OR 1.91, 95% CI 1.25-2.91, P = 0.003). Both CRA and control show no difference in the genotype of 1498C/T and the allele frequency of C-/T-. CRA patients with haplotype 1498T+936T presented significantly higher risk than those with wild-type 1498T+936C. Moreover, patients carrying 936CT+TT and 936-T allele demonstrated a tendency for villous adenoma. CRA patients have elevated plasma VEGF levels. The VEGF 936C/T polymorphism and 1498T+936T haplotype were found to be associated with increased CRA susceptibility.
Collapse
Affiliation(s)
- Xianglei Wu
- Department of Colorectal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei, China
| | | | | | | | | | | | | |
Collapse
|
|
29
|
Promthet SS, Pientong C, Ekalaksananan T, Wiangnon S, Poomphakwaen K, Songserm N, Chopjitt P, Moore MA, Tokudome S. Risk factors for colon cancer in Northeastern Thailand: interaction of MTHFR codon 677 and 1298 genotypes with environmental factors. J Epidemiol 2010; 20:329-38. [PMID: 20551579 PMCID: PMC3900794 DOI: 10.2188/jea.je20090140] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colon cancer risk and possible interactions with environmental factors in a population from northeastern Thailand. METHODS This hospital-based case-control study was conducted during 2002-2006; 130 colon cancer cases and 130 age- and sex-matched controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction with restriction fragment length polymorphism techniques. Associations between variables of interest and colon cancer were assessed using conditional logistic regression. RESULTS Increased risk of colon cancer was associated with alcohol consumption and bowel habits. Alcohol drinkers who consumed < or = 0.50 or >0.50 units of alcohol per day had elevated risks (OR(adj) = 3.5; 95% CI: 1.19-10.25 and OR(adj) = 1.71; 95% CI: 0.74-3.96, respectively). The risk was also higher in subjects with frequent constipation (11.69; 2.18-62.79) and occasional constipation (3.43; 1.72-6.82). An interaction was observed between the MTHFR C677T polymorphism and freshwater fish consumption on colon cancer risk (P value for interaction = 0.031). Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively). CONCLUSIONS In a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were also observed.
Collapse
|
|
30
|
Taioli E, Garza MA, Ahn YO, Bishop DT, Bost J, Budai B, Chen K, Gemignani F, Keku T, Lima CSP, Le Marchand L, Matsuo K, Moreno V, Plaschke J, Pufulete M, Thomas SB, Toffoli G, Wolf CR, Moore CG, Little J. Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. Am J Epidemiol 2009; 170:1207-21. [PMID: 19846566 DOI: 10.1093/aje/kwp275] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.
Collapse
Affiliation(s)
- E Taioli
- SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Figueiredo JC, Levine AJ, Grau MV, Midttun O, Ueland PM, Ahnen DJ, Barry EL, Tsang S, Munroe D, Ali I, Haile RW, Sandler RS, Baron JA. Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation. Cancer Epidemiol Biomarkers Prev 2008; 17:2136-45. [PMID: 18708408 DOI: 10.1158/1055-9965.epi-07-2895] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas. METHODS The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association. RESULTS We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all adenomas. CONCLUSION Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.
Collapse
Affiliation(s)
- Jane C Figueiredo
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Harlyne J Norris Cancer Research Tower, 1450 Biggy Street Room 1509B, Los Angeles CA 90033, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
de Vogel S, Dindore V, van Engeland M, Goldbohm RA, van den Brandt PA, Weijenberg MP. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008; 138:2372-8. [PMID: 19022960 DOI: 10.3945/jn.108.091157] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Adequate intake of folate, methionine, riboflavin, and vitamin B-6 may prevent aberrant DNA methylation and thereby protect against colorectal cancer (CRC). However, previous epidemiological studies investigating associations between dietary intakes of these nutrients and CRC have been inconsistent. We investigated the associations between intakes of folate, methionine, riboflavin, and vitamin B-6 and CRC risk, accounting for the sublocalization of the tumor. Within the Netherlands Cohort Study on diet and cancer (n = 120,852), 2349 cases and 4168 subcohort members were available for data analyses from a follow-up period of 13.3 y after baseline. Gender-specific adjusted incidence rate ratios (RR) were calculated over quintiles of dietary intake in case-cohort analyses. Folate intake was not associated with CRC risk in either men or women. However, methionine was associated with decreased risk of proximal colon cancer among men (RR = 0.57 for highest vs. lowest quintile of intake; P-trend = 0.03) and rectal cancer among women (highest vs. lowest quintile; RR = 0.45; P-trend = 0.05). Riboflavin tended to be associated with decreased proximal colon cancer risk among women (RR = 0.61; P-trend = 0.07). Conversely, there was a strong positive association between vitamin B-6 and rectal cancer among women (RR = 3.57; P-trend = 0.01). Our findings suggest that relatively high methionine intake may protect against proximal colon cancer in men and rectal cancer in women but that folate may not have a protective effect. This is the 2nd prospective cohort study in which vitamin B-6 intake was associated with increased risk of rectal tumors in women, which might suggest that this vitamin enhances rectal cancer in women.
Collapse
Affiliation(s)
- Stefan de Vogel
- Departments of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
| | | | | | | | | | | |
Collapse
|
|
33
|
Levine AJ, Wallace K, Tsang S, Haile RW, Saibil F, Ahnen D, Cole BF, Barry EL, Munroe DJ, Ali IU, Ueland P, Baron JA. MTHFR genotype and colorectal adenoma recurrence: data from a double-blind placebo-controlled clinical trial. Cancer Epidemiol Biomarkers Prev 2008; 17:2409-15. [PMID: 18768511 DOI: 10.1158/1055-9965.epi-07-2670] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. We assessed the association between two common MTHFR variants, 677C>T and 1298A>C, and adenoma recurrence in the context of a randomized double- blind clinical trial of aspirin use and folate supplementation. We used generalized linear regression to estimate risk ratios and 95% confidence intervals (95% CI) for recurrence, adjusting for age, sex, clinical center, follow-up time, and treatment status. Neither MTHFR polymorphism was associated with overall or advanced adenoma recurrence. Compared with those with two wild-type alleles, the relative risk for advanced adenoma was 0.75 (95% CI, 0.36-1.55) for the MTHFR 677 TT genotype and 1.16 (95% CI, 0.58-2.33) for the MTHFR 1298 CC genotype. The effect of folate supplementation on recurrence risk did not differ by genotype. Our findings indicate that the MTHFR genotype does not change adenoma risk in a manner similar to its effect on colorectal cancer, and does not modify the effect of folate supplementation on metachronous adenoma risk.
Collapse
Affiliation(s)
- A Joan Levine
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Pot GK, Geelen A, van Heijningen EMB, Siezen CL, van Kranen HJ, Kampman E. Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with colorectal adenoma risk: An endoscopy-based case-control study. Int J Cancer 2008; 123:1974-7. [DOI: 10.1002/ijc.23729] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
|
|
35
|
Abstract
Although folic acid has been investigated for its potential to inhibit carcinogenesis, few epidemiologic studies have assessed the effects of intake of thiamin, riboflavin, and niacin, which may reduce cancer risk by acting as cofactors in folate metabolism or by other mechanisms. Using data from a large cohort of Canadian women, we examined the association of dietary intake of these nutrients, as well as intake of folate, methionine, and alcohol, with cancers of the breast, endometrium, ovary, colorectum, and lung ascertained during an average of 16.4 years of follow-up. After exclusions, the following numbers of incident cases were available for analysis: breast, n=2491; endometrium, n=426; ovary, n=264; colorectum, n=617; and lung, n=358. Cox proportional hazard models were used to estimate risk of each cancer with individual nutrients and to explore possible effect modification by combinations of nutrients on cancer risk. Few significant associations of intake of individual B vitamins with the five cancers were observed. Alcohol consumption showed a modest positive association with breast cancer risk but not with risk of the other cancers. There was no evidence of effect modification among the nutrients. This large study provides little support for an association of dietary intake thiamin, riboflavin, niacin, folate, or methionine with five major cancers in women.
Collapse
|
|
36
|
Liu Z, Choi SW, Crott JW, Smith DE, Mason JB. Multiple B-vitamin inadequacy amplifies alterations induced by folate depletion in p53 expression and its downstream effector MDM2. Int J Cancer 2008; 123:519-25. [PMID: 18498130 DOI: 10.1002/ijc.23599] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Folate is required for biological methylation and nucleotide synthesis, aberrations of which are thought to be the mechanisms that enhance colorectal carcinogenesis produced by folate inadequacy. These functions of folate also depend on the availability of other B-vitamins that participate in "one-carbon metabolism," including B2, B6 and B12. Our study therefore investigated whether combined dietary restriction of these vitamins amplifies aberrations in the epigenetic and genetic integrity of the p53 gene that is induced by folate depletion alone. Ninety-six mice were group pair-fed diets with different combinations of B-vitamin depletion over 10 weeks. DNA and RNA were extracted from epithelial cells isolated from the colon. Within the hypermutable region of p53 (exons 5-8), DNA strand breaks were induced within exons 6 and 8 by folate combined with B2, B6 and B12 restriction (p < 0.05); such effects were not significantly induced by mild folate depletion alone. Similarly, a minor degree of hypomethylation of exon 6 produced by isolated folate depletion was significantly amplified (p < or = 0.05) by simultaneous depletion of all 4 B-vitamins. Furthermore, the expression of p53 and MDM2 were significantly decreased (p < or = 0.05) by the combined depletion state but not by folate depletion alone. These data indicate that inadequacies of other 1-carbon vitamins may amplify aberrations of the p53 gene induced by folate depletion alone, implying that concurrent inadequacies in several of these vitamins may have added tumorigenic potential beyond that observed with isolated folate depletion.
Collapse
Affiliation(s)
- Zhenhua Liu
- Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
| | | | | | | | | |
Collapse
|
|
37
|
Effect of Coenzyme Q10, Riboflavin and Niacin on Tamoxifen treated postmenopausal breast cancer women with special reference to blood chemistry profiles. Breast Cancer Res Treat 2008; 114:377-84. [DOI: 10.1007/s10549-008-0012-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2008] [Accepted: 04/04/2008] [Indexed: 10/22/2022]
|
|
38
|
Tijhuis MJ, Visker MHPW, Aarts JMMJG, Laan W, de Boer SY, Kok FJ, Kampman E. NQO1 and NFE2L2 polymorphisms, fruit and vegetable intake and smoking and the risk of colorectal adenomas in an endoscopy-based population. Int J Cancer 2008; 122:1842-8. [PMID: 18074351 DOI: 10.1002/ijc.23246] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
UNLABELLED Both environment and genetics contribute to the pathogenesis and prevention of colorectal neoplasia. NAD(P)H quinone oxidoreductase (NQO1) is a detoxification enzyme that is polymorphic and inducible. We investigated interactions between lifestyle factors and polymorphisms in NQO1 and its key regulatory transcription factor NFE2L2 in colorectal adenoma risk. The NQO1 c.609C>T and g.-718A>G and NFE2L2 g.-650C>A, g.-684G>A and g.-686A>G polymorphisms were determined among 740 Dutch adenoma cases and 698 endoscopy-based controls. Dietary intake was assessed by food frequency questionnaire, other lifestyle information by questionnaire. The NQO1 609CT genotype was associated with a higher adenoma risk (OR 1.27, 95% CI 1.00-1.62) compared with the 609CC genotype, whereas the 609TT genotype was not (OR 1.03, 95% CI 0.56-1.88). The higher risk with the NQO1 609CT-genotype was seen among smokers (OR 1.96, 95% CI 1.40-2.76), but not among nonsmokers (OR 0.91, 95% CI 0.62-1.35; interaction p = 0.030). Fruit and vegetable consumption did not protect smokers from adenomas and did not interact with the NQO1 609C>T polymorphism or the NFE2L2 polymorphisms. A higher adenoma risk seen with high fruit and vegetable consumption among NQO1 -718GG genotypes was absent among -718GA genotypes (interaction p = 0.071). Gene-gene interactions were observed between the NQO1 609C>T and NFE2L2 -686A>G polymorphisms (interaction p = 0.056) and between the NQO1 -718 G>A and NFE2L2 -650C>A polymorphisms (interaction p = 0.013). IN CONCLUSION the NQO1 609CT genotype is associated with increased adenoma risk among smokers, which is not diminished by high fruit and vegetable consumption. The observed gene-gene interactions may point to a role for NFE2L2 polymorphisms in NQO1-related adenoma formation.
Collapse
Affiliation(s)
- Mariken J Tijhuis
- Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
| | | | | | | | | | | | | |
Collapse
|
|
39
|
Murphy G, Sansbury LB, Cross AJ, Stolzenberg-Solomon R, Laiyemo A, Albert PS, Wang Z, Schatzkin A, Lehman T, Kalidindi A, Modali R, Lanza E. Folate and MTHFR: risk of adenoma recurrence in the Polyp Prevention Trial. Cancer Causes Control 2008; 19:751-8. [PMID: 18322814 DOI: 10.1007/s10552-008-9137-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2007] [Accepted: 02/15/2008] [Indexed: 11/26/2022]
Abstract
BACKGROUND Low dietary folate intake has been associated with colorectal cancer risk and adenoma recurrence. A C/T transition at position 677 in the gene encoding methlylenetetrahydrofolate reductase (MTHFR C677T) has been reported to interact with folate intake to modulate colorectal adenoma recurrence or cancer risk. METHODS We investigated the association between MTHFR, total folate, and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. We compared 625 individuals with any adenoma recurrence after 4 years (266 individuals with multiple (> or =2) recurrent adenomas and 101 individuals with advanced adenoma recurrence) to 978 individuals with no adenoma recurrence. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. We also investigated effect modification of the MTHFR genotype associations by total folate intake. RESULTS In general, no statistically significant associations were found between quartile of folate intake (dietary or total) and adenoma recurrence. The MTHFR CT genotype was associated with a significantly increased risk of multiple adenoma recurrence (OR: 1.34, 95% CI: 1.00, 1.81). No significant interaction was noted for total folate and MTHFR genotype, though an increased risk of recurrence noted for the MTHFR CT genotype was statistically significant only for those individuals with below median intake of total folate. CONCLUSION We report that the MTHFR 677 CT genotype was associated with increased risk of adenoma recurrence (specifically multiple adenoma recurrence) 4 years after polypectomy.
Collapse
Affiliation(s)
- Gwen Murphy
- Cancer Prevention Fellowship Program, Office of Preventive Oncology, Bethesda, MD, USA.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Botteri E, Iodice S, Raimondi S, Maisonneuve P, Lowenfels AB. Cigarette smoking and adenomatous polyps: a meta-analysis. Gastroenterology 2008; 134:388-95. [PMID: 18242207 DOI: 10.1053/j.gastro.2007.11.007] [Citation(s) in RCA: 222] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2007] [Accepted: 10/25/2007] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Through the past 2 decades, a consistent association between cigarette smoking and colorectal adenomatous polyps, recognized precursor lesions of colorectal cancer, has been shown. We performed a meta-analysis to provide a quantitative pooled risk estimate of the association, focusing on the different characteristics of the study populations, study designs, and clinical feature of the polyps. METHODS We performed a comprehensive literature search of studies linking cigarette smoking and adenomas. We used random effects models to evaluate pooled relative risks and performed dose-response, heterogeneity, publication bias, and sensitivity analyses. RESULTS Forty-two independent observational studies were included in the analysis. The pooled risk estimates for current, former, and ever smokers in comparison with never smokers were 2.14 (95% confidence interval [CI], 1.86-2.46), 1.47 (95% CI, 1.29-1.67), and 1.82 (95% CI, 1.65-2.00), respectively. The association was stronger for high-risk adenomas than for low-risk adenomas. Studies in which all controls underwent full colonoscopy showed a higher risk compared with studies in which some or all controls underwent partial colon examination. CONCLUSIONS This meta-analysis provides strong evidence of the detrimental effect of cigarette smoking on the development of adenomatous polyps. Smoking is important for both formation and aggressiveness of adenomas.
Collapse
Affiliation(s)
- Edoardo Botteri
- Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
| | | | | | | | | |
Collapse
|
|
41
|
Powers HJ, Hill MH, Welfare M, Spiers A, Bal W, Russell J, Duckworth Y, Gibney E, Williams EA, Mathers JC. Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study). Cancer Epidemiol Biomarkers Prev 2008; 16:2128-35. [PMID: 17932361 DOI: 10.1158/1055-9965.epi-07-0208] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Epidemiologic data suggest that increasing folate intake may protect against colorectal cancer. Riboflavin may interact with folate to modulate the effect. A double-blind randomized placebo-controlled intervention study (the FAB2 Study) was carried out in healthy controls and patients with colorectal polyps (adenomatous and hyperplastic) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk (DNA methylation and DNA damage; to be reported elsewhere). Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase, MTHFR C677T, and were randomized to receive 400 microg of folic acid, 1,200 microg of folic acid, or 400 microg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks. Blood samples and colon biopsy samples were collected for the measurement of biomarkers of folate and riboflavin status. Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate, and a marked increase in RBC and plasma, with a dose-response. Measures of riboflavin status improved in response to riboflavin supplementation. Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps. The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients. Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma, but with a suggestion of an upper limit.
Collapse
Affiliation(s)
- Hilary J Powers
- Human Nutrition Unit, Section of Oncology, University of Sheffield, UK.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Dhonukshe-Rutten RAM, de Vries JHM, de Bree A, van der Put N, van Staveren WA, de Groot LCPGM. Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. Eur J Clin Nutr 2007; 63:18-30. [PMID: 17851461 DOI: 10.1038/sj.ejcn.1602897] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND/OBJECTIVES Folate and vitamin B12 have been suggested to play a role in chronic diseases like cardiovascular diseases. The objectives are to give an overview of the actual intake and status of folate and vitamin B12 in general populations in Europe, and to evaluate these in view of the current vitamin recommendations and the homocysteine concentration. METHODS Searches in Medline with 'folic acid', 'folate' and 'vitamin B12', 'B12' or 'cobalamin' as key words were combined with the names of the European countries. Populations between 18 and 65 years were included. RESULTS Sixty-three articles reporting on studies from 15 European countries were selected. Low folate intakes were observed in Norway, Sweden, Denmark and the Netherlands. Low intakes of vitamin B12 were not common and only seen in one small Greek study. In the countries with a low intake of folate, the recommended levels were generally not achieved, which was also reflected in the folate status. Vitamin B12 intake was not strongly associated with the vitamin B12 status, which can explain why in the Netherlands and Germany the vitamin B12 status was inadequate, despite sufficient intake levels. In countries with a low folate intake in particular, the Hcy concentration was higher than ideal. CONCLUSIONS Populations from the Nordic countries, the Netherlands, Germany and Greece may need to improve their intakes of folic acid, B12 or both to either meet the recommendations or to optimize their statuses. This could be achieved via a food-based approach, food fortification or supplements.
Collapse
|
|
43
|
Pellis L, Dommels Y, Venema D, Polanen AV, Lips E, Baykus H, Kok F, Kampman E, Keijer J. High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Br J Nutr 2007; 99:703-8. [PMID: 17868486 DOI: 10.1017/s0007114507824147] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12and other micronutrients involved in the folate–methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.
Collapse
Affiliation(s)
- Linette Pellis
- RIKILT-Institute of Food Safety, PO Box 230, 6700 AE Wageningen, The Netherlands
| | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
van den Donk M, Pellis L, Crott JW, van Engeland M, Friederich P, Nagengast FM, van Bergeijk JD, de Boer SY, Mason JB, Kok FJ, Keijer J, Kampman E. Folic acid and vitamin B-12 supplementation does not favorably influence uracil incorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas. J Nutr 2007; 137:2114-20. [PMID: 17709451 DOI: 10.1093/jn/137.9.2114] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. The uracil concentration of DNA increased in the treated group (5.37 fmol/microg DNA, P = 0.02), whereas it did not change in the placebo group (P = 0.42). The change from baseline of 4.01 fmol uracil/microg DNA tended to differ between the groups (P = 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67; P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.
Collapse
Affiliation(s)
- Maureen van den Donk
- Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, The Netherlands
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Abstract
As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate "intake" or exposure to a specific food or bioactive component, that assess one or more specific biological "effects" that are linked to cancer, and that effectively predict individual "susceptibility" as a function of nutrient-nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics.
Collapse
Affiliation(s)
- Cindy D Davis
- Nutritional Science Research Group, National Cancer Institute, Rockville, MD 20892, USA.
| | | |
Collapse
|
|
46
|
van den Donk M, Visker MHPW, Harryvan JL, Kok FJ, Kampman E. Dietary intake of B-vitamins, polymorphisms in thymidylate synthase and serine hydroxymethyltransferase 1, and colorectal adenoma risk: A Dutch case-control study. Cancer Lett 2007; 250:146-53. [PMID: 17113224 DOI: 10.1016/j.canlet.2006.10.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2006] [Revised: 10/02/2006] [Accepted: 10/09/2006] [Indexed: 11/28/2022]
Abstract
Thymidylate synthase and serine hydroxymethyltransferase are involved in folate metabolism. In a case-control study, including 768 cases and 709 controls, we investigated the associations between colorectal adenomas and TS tandem repeat and SHMT1 C1420T polymorphisms, and the interplay with B-vitamins. The polymorphisms were not associated with adenomas, but there was a borderline significant interaction between TS genotype and vitamin B6: the association between vitamin B6 and adenomas seemed positive in TS 3R/3R individuals, but inverse in TS 2R/2R individuals. This study does not provide evidence for a role of SHMT1 genotype in adenoma occurrence. Future research has to indicate whether the TS-B6 interplay is a real effect or a chance finding.
Collapse
Affiliation(s)
- Maureen van den Donk
- Division of Human Nutrition, Wageningen University, P.O. Box 8129, NL-6700 EV Wageningen, The Netherlands
| | | | | | | | | |
Collapse
|
|
47
|
Premkumar VG, Yuvaraj S, Vijayasarathy K, Gangadaran SGD, Sachdanandam P. Effect of coenzyme Q10, riboflavin and niacin on serum CEA and CA 15-3 levels in breast cancer patients undergoing tamoxifen therapy. Biol Pharm Bull 2007; 30:367-70. [PMID: 17268082 DOI: 10.1248/bpb.30.367] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In breast cancer patients, it is not the primary tumour, but its metastases at distant sites that are the main cause of death. Circulating breast cancer tumour markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) are reliable indicators of impending relapse, in which an increasing tumour marker level is associated with a very likelihood of developing recurrence. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of 100 mg coenzyme Q10 (CoQ10), 10 mg riboflavin and 50 mg niacin (CoRN) one dosage per day along with 10 mg tamoxifen (TAM) twice a day. Serum CEA and CA 15-3 levels were elevated in untreated breast cancer patients (group II) and their tumour marker levels significantly reduced upon tamoxifen therapy for more than 1 year (group III). Group III patients supplemented with CoRN for 45 d (group IV) and 90 d (group V) along with tamoxifen significantly reduced CEA and CA 15-3 levels. This study suggests supplementing CoRN to breast cancer patients along with tamoxifen reduces the serum tumour marker level and thereby reduce the risk of cancer recurrence and metastases.
Collapse
Affiliation(s)
- Vummidi Giridhar Premkumar
- Department of Medical Biochemistry, Dr. ALMP-GIBMS, University of Madras, Taramani Campus, and Department of Medical Oncology, Government Royapettah Hospital, Tamilnadu, India
| | | | | | | | | |
Collapse
|
|
48
|
van den Donk M, van Engeland M, Pellis L, Witteman BJM, Kok FJ, Keijer J, Kampman E. Dietary folate intake in combination with MTHFR C677T genotype and promoter methylation of tumor suppressor and DNA repair genes in sporadic colorectal adenomas. Cancer Epidemiol Biomarkers Prev 2007; 16:327-33. [PMID: 17301267 DOI: 10.1158/1055-9965.epi-06-0810] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Methylation of the promoter region of tumor suppressor genes is increasingly recognized to play a role in cancer development through silencing of gene transcription. We examined the associations between dietary folate intake, MTHFR C677T genotype, and promoter methylation of six tumor suppressor and DNA repair genes. Patients with colorectal adenoma (n = 149) and controls (n = 286) with folate intake in the upper or lower tertile with the CC or TT genotype were selected from a case-control study. Methylation-specific PCRs were conducted on colorectal adenoma specimens. The percentages of promoter methylation ranged from 15.7% to 64.2%. In case-case comparisons, folate was inversely associated with promoter methylation, especially among TT homozygotes. Case-control comparisons suggested that folate was not associated with the occurrence of adenomas with promoter methylation, and increased the risk of unmethylated adenomas, especially in TT homozygotes. The interactions between folate and MTHFR genotype were most pronounced for O(6)-MGMT: compared with CC homozygotes with low folate intake, the adjusted odds ratios (95% confidence interval) of having a methylated O(6)-MGMT promoter were 3.39 (0.82-13.93) for TT homozygotes with low folate intake and 0.37 (0.11-1.29) for TT homozygotes with high folate intake (P interaction = 0.02); the odds ratios for the occurrence of adenomas without methylation were 0.57 (0.16-2.11) for TT homozygotes with low folate intake and 3.37 (1.17-9.68) for TT homozygotes with high folate intake (P interaction = 0.03). In conclusion, folate intake seems to be inversely associated with promoter methylation in colorectal adenomas in case-case comparisons, and was positively associated with the occurrence of adenomas without promoter methylation in case-control comparisons, especially for TT homozygotes.
Collapse
Affiliation(s)
- Maureen van den Donk
- Division of Human Nutrition, Wageningen University, P.O. Box 8129, NL-6700 EV Wageningen, the Netherlands
| | | | | | | | | | | | | |
Collapse
|
|
49
|
|
|
50
|
Martínez ME, Thompson P, Jacobs ET, Giovannucci E, Jiang R, Klimecki W, Alberts DS. Dietary factors and biomarkers involved in the methylenetetrahydrofolate reductase genotype-colorectal adenoma pathway. Gastroenterology 2006; 131:1706-16. [PMID: 17087956 DOI: 10.1053/j.gastro.2006.09.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2006] [Accepted: 08/17/2006] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate homeostasis and metabolism. We assessed 2 polymorphisms in the MTHFR gene (C677T and A1298C) in relation to colorectal adenoma recurrence and conducted analyses to investigate their joint effects with plasma and dietary markers of folate status. METHODS We prospectively analyzed data from 1598 individuals genotyped for the C677T polymorphism and 1583 with data on A1298C. RESULTS Among nonusers of multivitamin supplements, compared with wild-type carriage, higher odds of recurrence were observed for those with the 677 TT variant (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.04-2.63) and a nonsignificant increase was observed among those with the 1298 CC variant (OR, 1.50; 95% CI, 0.93-2.40). Diplotype analyses among nonusers of multivitamins showed that individuals who carry the MTHFR 677TT_1298AA or 677CC_1298CC combination were significantly more likely to have a recurrence compared with those with the double wild-type (OR, 2.05 for TT_AA and 1.85 for CC_CC). Higher odds of recurrence were observed among participants with low folate intake or plasma folate and the 677 TT or 1298 CC variants compared with those with lower levels and the wild-type or heterozygous genotypes. Stronger associations were shown for the combination of high homocysteine and the 677 TT variant (OR, 2.29; 95% CI, 1.00-5.26) but not the 1298 CC variant (OR, 1.09; 95% CI, 0.39-3.01). CONCLUSIONS We propose that the effect of the MTHFR genotypes on increasing risk of adenoma recurrence in the presence of a low folate status is through their increase in homocysteine concentrations, which in turn could result in DNA hypomethylation via pathways involving S-adenosylhomocysteine.
Collapse
|