Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B&lt;sub&gt;12&lt;/sub&gt;

Ebbing, Marta; Bønaa, Kaare Harald; Nygård, Ottar; Arnesen, Egil; Ueland, Per Magne; Nordrehaug, Jan Erik; Rasmussen, Knut; Njølstad, Inger; Refsum, Helga; Nilsen, Dennis W.T.; Tverdal, Aage; Meyer, Klaus; Vollset, Stein Emil

doi:10.1001/jama.2009.1622

Cited by 372 publications

(302 citation statements)

References 36 publications

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“…Genetic analyses focussed on MTHFR, MTR and MTRR because single-nucleotide polymorphisms (SNPs) in these genes have been shown to affect enzyme activity, and there is most evidence for a potential role in cancer development (Ebbing et al, 2009). We included the most frequently studied SNPs (MTHFR: A1298C, rs1801131 and C677T, rs1801133; MTR: A2756G, rs1805087 and MTRR: A66G, rs18011394) and selected other SNPs for study using the TAMAL online tag SNP selection tool (Hemminger et al, 2006), using default parameters with the TAGGER method of selection from the Caucasian HapMap population.…”

Section: Methodsmentioning

confidence: 99%

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer

et al. 2011

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Background/Objective: Folates are essential for DNA synthesis and methylation, and thus may have a role in carcinogenesis. Limited evidence suggests folate-containing foods might protect against some cancers and may partially mitigate the increased risk of breast cancer associated with alcohol intake, but there is little information regarding ovarian cancer. Our aim was to evaluate the role of folate and related micronutrients, polymorphisms in key folate-metabolising genes and environmental factors in ovarian carcinogenesis. Subjects/Methods: Participants in the Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires. DNA samples (1638 cases, 1278 controls) were genotyped for 49 tag single-nucleotide polymorphisms (SNPs) in the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) genes. Logistic regression models were used to generate adjusted odds ratios and 95% confidence intervals. Results: We saw no overall association between the intake of folate, B vitamins or other methyl donors and ovarian cancer risk, although increasing folate from foods was associated with reduced risk among current smokers (P trend ¼ 0.03) and folic acid intake was associated with borderline significant increased risks among women who consumed X1 standard alcoholic drinks/ day (odds ratio (OR) ¼ 1.64; 95% confidence interval (CI) 1.05-2.54, P trend ¼ 0.05). Two SNPs (rs7365052, rs7526063) showed borderline significant inverse associations with ovarian cancer risk; both had very low minor allele frequencies. There was little evidence for interaction between genotype and micronutrient intake or for variation between different histological subtypes of ovarian cancer. Conclusions: Our data provide little evidence to support a protective role for folate in ovarian carcinogenesis but suggest further evaluation of the joint effects of folic acid and alcohol is warranted.

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Section: Methodsmentioning

confidence: 99%

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer

et al. 2011

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“…One of the key dietary factors in this regard is folate, a vitamin that is given in large quantities to pregnant women (to reduce the risk of neural tube defects) and as supplemental content within the U.S. food supply as well. Folate supplementation has come under fire recently, with some studies raising safety concerns by showing an association with an increased incidence of and/or mortality from various cancers (18). Furthermore, laboratory research has linked high levels of folate with accelerated age-related DNA methylation (19), leading one to wonder whether diet could have had an influence on the constitutional methylation as reported by Wong et al (3).…”

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confidence: 99%

Time to Think Outside the (Genetic) Box

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Garber

2011

Cancer Prevention Research

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Many patients develop cancers that have clinical features of inherited syndromes (e.g., young age of onset and unique pathology) but lack mutations in the genes characteristic of the disease. In this issue of the journal, Wong et al. report that somatic epigenetic inactivation could explain some such cases in the setting of BRCA1-associated breast cancer. Here, we discuss the implications of this work in terms of the etiology, risk, and potential prevention of cancer. Cancer Prev Res; 4(1); 6-8. Ó2011 AACR.Identification of high-risk populations is a research priority in cancer prevention. Genetic predisposition to cancer development is an obvious marker for risk, and several interventions have been shown to reduce cancer mortality in this group of patients. It remains puzzling, however, that despite more than 2 decades of research into mutations in the genes most commonly responsible for inherited cancer, such mutations are not found in a large number of cases that share clinical criteria for having inherited cancer (young age at onset, specific pathology, etc.; ref. 1). For many years, this absence of mutations was easy to explain away-our knowledge of cancer genetics was thought to be fragmentary, and these puzzling cases were assumed to carry mutations in genes yet to be identified. However, large-scale sequencing efforts in major human malignancies such as colorectal cancer (2) have not uncovered previously unknown high-frequency mutations. We are left, therefore, with the somewhat unsatisfying hypothesis that rare mutations in multiple genes or a combination of alterations in several genes that act collectively underlie the many cases of inherited cancer with no known cancerassociated mutation.In this issue of the journal, Wong et al. (3) present data supporting an alternative concept: that is, constitutional epigenetic defects can account for a significant proportion of cancers with the clinical/pathologic features but not the characteristic mutations of inherited cancers. This study was conducted in 255 female breast cancer patients without an identified germline BRCA1 (or BRCA2) mutation and 169 age-matched female controls. The breast cancers in the cases were required to share certain features of inherited BRCA1-associated disease [onset at a young patient age (<40 years), and aggressive pathology). The patients were assessed for 9 tumor pathology features deemed to be characteristic of cancers in BRCA1 mutation carriers and then were divided into 3 groups, as follows: 5 or more characteristic features (group 1), 4 features (group 2), and 3 or fewer features (group 3). Thirty-one percent of the patients with the most BRCA1-like tumors (group 1) had detectable BRCA1 methylation in peripheral bloodderived DNA, and the cancers themselves had high levels of BRCA1 methylation. The frequency of peripheral blood BRCA1 methylation was much lower (5%) in patients whose cancers had fewer BRCA1 features (group 3), and the non-BRCA1-like cancers themselves had low levels of BRCA1 methylation. There was an ...

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“…31 Yajnik et al 32 reported that children whose mothers had high folate and low vitamin B12 levels during pregnancy had the highest risk of insulin-resistance, compared with those whose mothers who only had low B12 or high folate (but both of those groups had higher levels than did those whose mothers had normal B12 and folate). Increased folate levels have also been associated with increased lung cancer risk 33 ; reduced natural killer cell cytotoxicity 34 ; and, in the presence of concomitant low B12, anemia and cognitive impairment in the elderly. 35 It has been suggested that there may be increased risk for certain cancers in the presence of high folate levels, although there is no clear evidence confirming these observations.…”

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confidence: 99%

Policy statement on folic acid and neural tube defects

Toriello

2011

Genetics in Medicine

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Disclaimer: ACMG standards and guidelines are designed primarily as an educational resource for medical geneticists and other healthcare providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticists should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines.

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Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B<sub>12</sub>

Cited by 372 publications

References 36 publications

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer

Time to Think Outside the (Genetic) Box

Policy statement on folic acid and neural tube defects

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