Methionine and Vitamin B6 Intake and Risk of Pancreatic Cancer: A Prospective Study of Swedish Women and Men

doi:10.1053/j.gastro.2006.10.017

Gastroenterology

Volume 132, Issue 1, January 2007, Pages 113-118

https://doi.org/10.1053/j.gastro.2006.10.017 Get rights and content

Background & Aims: It has been hypothesized that dietary factors involved in methyl group metabolism, such as methionine, folate, and vitamin B₆, may modify cancer risk. We have previously reported an inverse association between folate intake and pancreatic cancer risk in a prospective population-based cohort of Swedish women and men. In the present study, we used data from this prospective study to examine whether methionine and vitamin B₆ intakes were associated with the incidence of exocrine pancreatic cancer. Methods: Our study population comprised 81,922 Swedish women and men, aged 45–83 years, who were free from cancer and completed a self-administered food-frequency questionnaire in 1997. We used Cox proportional hazards models to estimate rate ratios with 95% confidence intervals (CI), adjusted for age, sex, education, smoking, body mass index, diabetes, and intakes of total energy and dietary folate. Results: During a mean follow-up of 7.2 years, through June 2005, 147 incident cases of pancreatic cancer were diagnosed. Methionine intake was significantly inversely associated with risk of pancreatic cancer, whereas no significant association was observed for dietary or total vitamin B₆ intake. The multivariate rate ratios comparing the highest with the lowest quartile of methionine intake were 0.44 (95% CI, 0.26–0.73; P for trend = .0005) in women and men combined, 0.59 (95% CI, 0.28–1.21; P for trend = .07) in women, and 0.32 (95% CI, 0.15–0.65; P for trend = .002) in men. Conclusions: These findings suggest that higher methionine intake may reduce the risk of pancreatic cancer.

Section snippets

Study Population

The Swedish Mammography Cohort was established between 1987 and 1990, when all women born between 1914 and 1948 and residing in central Sweden (Västmanland and Uppsala counties) were mailed a questionnaire on diet, weight, height, and education. In the autumn of 1997, all living participants received a new questionnaire that was expanded to include about 350 items concerning diet and other lifestyle factors (including cigarette smoking), dietary supplement use, and medical history; 39,227 women

Results

As of June 30, 2005 (mean follow-up, 7.2 years), 147 participants (65 women and 82 men) had been diagnosed with exocrine pancreatic cancer. Compared with women and men in the lowest quartile of methionine intake, those in the highest quartile were more likely to have a history of diabetes and had a higher folate intake (Table 1). Those in the highest quartiles of dietary and total vitamin B₆ intakes were, on average, younger and more likely to have a postsecondary education, to be nonsmokers,

Discussion

In this prospective study of Swedish women and men, we observed an inverse dose-response relationship between methionine intake and risk of pancreatic cancer. Foods rich in methionine include fish, poultry, meat, legumes, and dairy products. No association was found between intake of vitamin B₆ and risk of pancreatic cancer.

Strengths of our study include its prospective and population-based design, high rates of follow-up, and detailed information on diet as well as potential risk factors for

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Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (−0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results.
Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.
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Two other case–control studies observed that the use of B6 was adversely related to head and neck cancer [19,20]. Additionally, a variety of similar studies reported protective associations between vitamin B6 intake and the risk of breast, ovarian, endometrial, esophageal, colorectal, prostate, pancreatic, and bladder cancer [10–14,21–25]. Notably, these studies only analyzed B6 from food sources, the level of which was often relatively low.
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Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.
Dietary Intake of Homocysteine Metabolism-Related B-Vitamins and the Risk of Stroke: A Dose-Response Meta-Analysis of Prospective Studies
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Observational studies regarding the putative associations between dietary intake of homocysteine metabolism-related B-vitamins (vitamin B-6, folate, and vitamin B-12) and stroke risk have yielded inconsistent results. Thus, we conducted a systematic meta-analysis of prospective studies in order to examine the relation between the dietary (from diet and supplements) intake of these B-vitamins and the risk of stroke. PubMed and Web of Science were searched for relevant articles published through to 25 February, 2020, and RR of stroke in relation to dietary intake of vitamin B-6, folate, and vitamin B-12 were pooled using a random-effects model. Eleven publications of 12 prospective studies comprising 389,938 participants and 10,749 cases were included in the final analysis. We found that dietary intake of vitamin B-6 and folate were associated with a reduced risk of stroke, and this inverse association remained significant in studies with >10 y of follow-up periods and among participants without a pre-existing stroke event. A dose-response analysis revealed a linear inverse association between folate and vitamin B-6 intake and the risk of stroke, with a pooled RR of 0.94 (95% CI: 0.90–0.98) and 0.94 (95% CI: 0.89–0.99) for each 100 μg/d increment in folate intake and 0.5 mg/d increment in vitamin B-6 intake, respectively. In contrast, we found no significant association between dietary vitamin B-12 intake and the risk of stroke, with an RR of 1.01 (95% CI: 0.97–1.06) per 3 μg/d increase. In conclusion, our findings suggest that increased intake of vitamin B-6 and folate is associated with a reduced risk of stroke, supporting the notion that increasing habitual folate and vitamin B-6 intake may provide a small but beneficial effect with respect to stroke.
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Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common determinant of serum homocysteine and folate status that is associated with increased risk for many cancers. This MTHFR deficiency in pancreatic cancer (PC) pathogenesis has been attributed to genetic polymorphism of MTHFR 677C>T and 1298A>C, but the evidence is still unclear. We conducted a meta-analysis of studies evaluating the effect of these polymorphisms on PC. We searched databases such as PubMed, Embase, and Google Scholar to retrieve studies that investigated MTHFR 677C>T and 1298A>C polymorphism for PC risk. For MTHFR 677C>T analysis, a total of eight publications with 1680 cases and 2520 controls were included; and for MTHFR 1298A>C analysis, six studies with 1421 cases and 1641 controls were included. Genotypes retrieved were subjected to meta-analysis using a random- or fixed-effects model with odds ratios and 95% confidence intervals as effect measures. Our met-analysis in all genetic models showed that MTHFR polymorphisms were not associated with the risk for PC. MTHFR polymorphisms revealed significant heterogeneity between studies for MTHFR 677C>T (P = .003) but not for 1298A>C (P = .495). Furthermore, there was no evidence for publication bias for these polymorphisms. Because the distribution of MTHFR genetic polymorphism differs among ethnic groups, the results of this meta-analysis cannot be extrapolated to patients belonging to any other ethnic group.
The association of fasting plasma sulfur-containing compounds with BMI, serum lipids and apolipoproteins
2012, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
Our data raises the possibility that increased sulfur amino acid availability may also be harmful. This supports reports from large studies showing increased acute coronary events [35] and diabetes [44] in subjects with higher methionine intake. Further, we recently observed profound effects of dietary cysteine on the key lipid enzyme stearoyl-coenzyme A desaturase and fatty acid profile in a rat model [45].
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Citation Excerpt :
Serum methionine was previously reported to be inversely associated with lung cancer; in that study, the effects were consistent across sex and years of follow-up.29 Dietary methionine intake based on food questionnaires was inversely associated with pancreatic cancer risk in a Swedish cohort study.30 The ATBC7 and the US Health Professional and Nurses’ Health cohort9 reported a null association between methionine intake and pancreatic cancer risk.
Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5′-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case–control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992–2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (±1 year), date (±1 year) and time (±3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ⩽5, 5–10, 10–15 (reference), 15–20, and >20 nmol/L were 1.58 (95% CI = 0.72–3.46), 1.39 (0.93–2.08), 1.0 (reference), 0.79 (0.52–1.21), and 1.34 (0.89–2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00–1.38) but not in women (OR = 0.91, 95% CI = 0.78–1.07; p for heterogeneity <0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

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: Supported by research grants from the Swedish Cancer Foundation and the Swedish Research Council/Longitudinal Studies.

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Clinical–liver, pancreas, and biliary tractMethionine and Vitamin B6 Intake and Risk of Pancreatic Cancer: A Prospective Study of Swedish Women and Men

Section snippets

Study Population

Results

Discussion

J Nutr

J Nutr

Biochem Biophys Res Commun

Am J Clin Nutr

Am J Clin Nutr

J Nutr

J Nutr

J Nutr

Am J Clin Nutr

Am J Clin Nutr

Cancer Lett

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men

J Natl Cancer Inst

Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers

J Natl Cancer Inst

Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers

Am J Epidemiol

A prospective study of folate intake and the risk of pancreatic cancer in men and women

Am J Epidemiol

A case-control study of diet and cancer of the pancreas

Am J Epidemiol

Clinical–liver, pancreas, and biliary tract
Methionine and Vitamin B₆ Intake and Risk of Pancreatic Cancer: A Prospective Study of Swedish Women and Men