Plasma B‐vitamin and one‐carbon metabolites and risk of breast cancer before and after folic acid fortification in the United States

• Published in: International journal of cancer 2019-04, Vol.144 (8), p.1929-1940
• Main Authors: Houghton, Serena C., Eliassen, A. Heather, Zhang, Shumin M., Selhub, Jacob, Rosner, Bernard A., Willett, Walter C., Hankinson, Susan E.
• Format: Article
• Language: English
• Subjects: Adult; Blood; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - epidemiology; Cancer; Carbon - metabolism; Case-Control Studies; Cysteine; Cysteine - blood; Dipeptides - blood; Female; Folic acid; Folic Acid - administration & dosage; Folic Acid - blood; folic acid fortification; Follow-Up Studies; Health risk assessment; Health risks; Homocysteine; Homocysteine - blood; Humans; Incidence; Invasiveness; Medical personnel; Medical research; Metabolites; Middle Aged; molecular subtypes; plasma B‐vitamins; plasma Folate; Prospective Studies; Pyridoxal Phosphate - blood; Risk factors; United States - epidemiology; Vitamin B; Vitamin B 12 - blood; Vitamins
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.31934

Prior epidemiologic findings for plasma folate and B‐vitamins and breast cancer risk are inconsistent and have not assessed the influence of folic acid fortification. Therefore, we examined the associations of plasma folate, B12, pyridoxal 5′‐phosphate (PLP), homocysteine, cysteine and cysteinylglycine with breast cancer risk, before and after fortification. We conducted a nested case–control study within the prospective Nurses’ Health Study. In 1989–1990 (pre‐fortification), 32,826 women donated a blood sample and 18,743 donated an additional blood sample in 2000–2001 (post‐fortification). Between the first blood collection and 2006, 1874 incident breast cancer cases with at least one blood sample and 367 with two were 1:1 matched to controls. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) adjusting for breast cancer risk factors. Overall, higher plasma folate, B12, PLP, homocysteine, cysteine and cysteinylglycine levels were not associated with breast cancer risk. Associations did not vary by in situ/invasive, hormone receptor status, or tumor molecular subtype. Additionally, associations were null before and after fortification. For example, the RR (95% CI) for the highest versus lowest tertile of 1990 (pre‐fortification) plasma folate with 1990–2000 follow‐up was 0.93 (0.75–1.16) and for the 2000 plasma folate (post‐fortification) with 2000–2006 follow‐up the RR (95% CI) was 1.17 (0.79–1.74). Plasma folate, B12, PLP, homocysteine, cysteine and cysteinylglycine were not significantly associated with breast cancer overall, before and after fortification, or with specific tumor molecular subtypes. However, long term associations (>8 years) after the implementation of fortification could not be examined. What's new? With concerns of increased cancer risk, there has been discussion as to whether countries should implement folic acid fortification programs. However, few prospective studies have examined plasma folate and other B‐vitamins levels and breast cancer risk among populations whose food is fortified with folic acid. This study examines the association of plasma folate and other B‐vitamins on breast cancer risk, prior to and after mandatory folic acid fortification of grain products in the U.S. Plasma folate, B12, PLP, homocysteine, cysteine, and cysteinylglycine were not significantly associated with breast cancer overall, before and after fortification, or with specific tumor molecular sub