1 1 The relationship between vitamin B6 and colonrectal cancer risk 維生素 B6 與大腸癌罹患風險之關係 實習生：王培竹 指導營養師：林京美 營養師 報告日期： 2012/12/25

2 Vitamin B6 Vitamin B6 is a water-soluble vitamin present in the human body as pyridoxine, pyridoxal, and pyridoxamine RDI ： – 1.4 mg/d (♂) – 1.2 mg/d (♀) The main dietary sources ： – poultry, fish, and meat – whole grains, legumes, and nuts

3 Vitamin B6 Regulation ： – oxidative stress – immune system – carcinogenesis Low levels of vitamin B6 ： – cell proliferation ↑ – C-reactive protein ↑ – oxidative stress ↑ – nitric oxide synthesis ↑ – angiogenesis ↑ aberrations in DNA methylation imbalance in DNA precursors disruption in DNA repair

44 Vitamin B6  One-carbon metabolism Vitamin B6 Folic acid OxidationDetoxification DNA synthesis DNA methylation MTHFR Vitamin B12 J.E. de Wit, 2011

55 CRC risk Plasma Vit.B Dietary Vit.B6 Plasma Vit.B6 CRC ： colorectal cancer

66 Dietary vitamin B6 intake and the risk of colorectal cancer Theodoratou E, et al. Cancer Epidemiol Biomarkers Prev. 2008;17(1):171–82.

7 Background evaluate the effect of dietary and supplementary intake of vitamin B6 on CRC and to investigate whether vitamin B6 effects are modified by folate and alcohol intakes.

88 Exclusions death before ascertainment too ill to participate recurrent cases unable to give informed consent ( learning difficulties or other Medical conditions.) macronutrients, micronutrients CRC n=2028, yr No-CRC n=2722, yr Information question (lifestyle, cancer) Semiquantitative FFQ (150 foods) ≦ 55 yr MTHFR, MTR, MTRR genotypes DNA samples were accurately quantified by PicoGreen CRC n=1001 No-CRC n=1010

9

10 Approximately 20%-30% reduction in risk for those of high versus those of low intake Intakes of dietary and of total Vit.B6 showed a significant inverse, and dose-dependent effect on CRC risk in all models.

11 Vit.B6 (dietary and total) had a similar strong inverse association with both colon, rectal, proximal, and distal cancer.

12 Vit.B6 effect was stronger among females.

13 Vit.B6 effect was stronger among ≦ 55 years.

14 Vit.B6 inverse association was of similar strength when adjusting for folate.

15 None of the polymorphisms was significantly associated with CRC

16

17 Discussion Intakes of dietary vitamin B6 showed a significant, inverse, and dose-dependent effect on CRC risk. Intakes of Vitamin B6 supplement did not effect (associated) on CRC risk. The high dietary vitamin B6 intake from food and/or supplements had a lower CRC risk. Gene polymorphisms was not significantly associated with CRC. Folate and alcohol did not affect the relationship between vitamin B6 and CRC risk.

18 Prospective study of plasma vitamin B6 and risk of colorectal cancer in men Lee JE, et al. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1197–202.

19 Background evaluate the effect of plasma PLP on CRC and whether the association for plasma PLP was independent of plasma levels of one-carbon metabolites and markers of inflammation, including CRP, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6.

20 Exclusions myocardial infarction stroke transient ischemic attack cancer (except nonmelanoma skin cancer) renal or liver disease peptic ulcer gout used vitamin A supplements used β -carotene supplements No-CRC, n=371 Physicians ’ Health Study n=22071 PLP, Vit.B12, folate Homocysteine, cysteine TNF- α R2, CRP, IL-6 MTHFR C677T CRC, n=197 Randomized, double-blind, placebo-controlled tial (aspirin and β-carotene ) Self-administered questionnaires 12 or 18 m FFQ Blood sample, n=14196 ( ) Blood sample

21

22

23 A lower rick of colorectal cancer was observed mainly among participants in the two higher quartiles.

24 Discussion The significant inverse association between plasma PLP levels and CRC risk. MTHFR C677T, inflammatory markers, folate, alcohol, multivitamin, aspirin, beta carotene, and BMI did not affect the relationship between PLP and CRC risk.

25 Plasma levels of B vitamins and colorectal cancer risk: the multiethnic cohort study Le Marchand L, et al. Cancer Epidemiol Biomarkers Prev. 2009;18(8):2195–201

26 Background comprehensively investigate the relationships of plasma folate, pyridoxal-5′-phosphate (PLP, the active form of vitamin B6), vitamin B12, methylmalonic acid, homocysteine, and cysteine with colorectal cancer risk, accounting for suspected modifiers (alcohol intake, MTHFR C677T genotype, and plasma CRP) and potential confounders.

27 Blood sample PLP, Vit.B12, folate MMA, homocysteine, cysteine CRP MTHFR C677T The multethnic cohort study n= ≧ 215, page baseline questionnaire FFQ Blood sample, n=67594 ( ) No-CRC, n=411 CRC, n=

28 12% ＞ 10% 60% ＞ 54% 23% ＞ 11% 57% ＞ 52% ＞ ＞ ＞ ＜ ＜

29

30

31

32

33 Discussion The significant inverse association between plasma PLP levels and CRC risk. The higher plasma folate can reduce CRC risk. Vitamin B12, MMA, cysteine, homocysteine was not significantly associated with CRC risk. MTHFR C677T, CRP, alcohol did not significant affect the relationship between PLP and CRC risk.

34 CRC risk Plasma Vit.B Dietary Vit.B6 Plasma Vit.B6 ( - ) association with LPL and folate ( - ) association 34 ( - ) association

35 Summary Finding that higher vitamin B6 intake and plasma PLP levels are associated with a lower risk of colorectal cancer, which is associated with a lower risk of colorectal cancer independent of other one-carbon metabolites, inflammatory biomarkers, MTHFR C677T and alcohol. the significant inverse association between vitamin B6 levels and CRC risk

36