The relationship between vitamin B6 and colonrectal cancer risk 維生素 B6 與大腸癌罹患風險之關係

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 1

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

4. Vitamin B6 One-carbon metabolism 4 DNA synthesis Folic acid Vitamin B6 Vitamin B12 DNA methylation MTHFR Vitamin B6 Vitamin B6 Detoxification Oxidation J.E. de Wit, 2011

5. 5 Dietary Vit.B6 CRC risk Plasma Vit.B Plasma Vit.B6 CRC ：colorectal cancer

6. Dietary vitamin B6 intake and the risk of colorectal cancer Theodoratou E, et al. Cancer Epidemiol Biomarkers Prev. 2008;17(1):171–82. 6

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.

8. 8 No-CRC n=2722, 16-79 yr CRC n=2028, 16-79 yr ≦55 yr Information question (lifestyle, cancer) Semiquantitative FFQ (150 foods) No-CRC n=1010 CRC n=1001 macronutrients, micronutrients DNA samples were accurately quantified by PicoGreen MTHFR, MTR, MTRR genotypes • Exclusions • death before ascertainment • too ill to participate • recurrent cases • unable to give informed consent ( learning difficulties or other Medical conditions.)

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

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

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. 18

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. 20 Physicians’ Health Study n=22071 1982 Randomized, double-blind, placebo-controlled tial (aspirin and β-carotene ) • Self-administered questionnaires • 12 or 18 m FFQ • Blood sample, n=14196 (1982-84) No-CRC, n=371 CRC, n=197 2000 Blood sample • PLP , Vit.B12, folate • Homocysteine , cysteine • TNF- α R2 , CRP , IL-6 • MTHFR C677T • 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

22. 顯著負相關 顯著正相關

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 25

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. 27 The multethnic cohort study n=≧215,000 • 26-page baseline questionnaire • FFQ • Blood sample, n=67594 (2001-06) 2006 CRC, n=224 No-CRC, n=411 Blood sample • PLP, Vit.B12, folate • MMA, homocysteine, cysteine • CRP • MTHFR C677T

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

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

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

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