Plasma Riboflavin and Vitamin B-6, but Not Homocysteine, Folate, or Vitamin B-12, Are Inversely Associated with Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition-Varese Cohort.
One-carbon metabolism-important for DNA stability and integrity-may play a role in breast carcinogenesis. However, epidemiologic studies addressing this issue have yielded inconsistent results.



We prospectively investigated associations between breast cancer and plasma folate, riboflavin, vitamin B-6, vitamin B-12, and homocysteine in women recruited to the Varese (Italy) cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition) study.



We performed a nested case-control study on women aged 35-65 y at recruitment with a median body mass index of 25.3 kg/m(2) who gave blood samples in 1987-1992 and again in 1993-1998. Breast cancer cases identified by 31 December 2009 were individually matched to controls. RRs of breast cancer (and subtypes defined by hormone receptor status) with 95% CIs were estimated by unconditional logistic regression, controlling for matching factors and breast cancer risk factors.



After a median of 14.9 y, 276 breast cancer cases were identified and matched to 276 controls. Increasing plasma vitamin B-6 was associated with decreased risk of overall (RR: 0.78; 95% CI: 0.63, 0.96 for 1-SD increase), premenopausal (RR: 0.66; 95% CI: 0.48, 0.92 for 1-SD increase), estrogen receptor-positive (RR: 0.79; 95% CI: 0.63, 1.00 for 1-SD increase), and progesterone receptor-positive (RR: 0.72; 95% CI: 0.55, 0.95 for 1-SD increase) breast cancers. Increased plasma vitamin B-6 was also associated with decreased breast cancer risk in alcohol consumers (≥7 g/d) compared with consumption of <7 g/d or nonconsumption (RR: 0.71; 95% CI: 0.51, 0.99). High plasma riboflavin was associated with significantly lower risk in premenopausal women (RR: 0.45; 95% CI: 0.21, 0.94; highest compared with the lowest quartile, P trend = 0.021). Plasma homocysteine, folate, and vitamin B-12 were not associated with breast cancer risk.



High plasma vitamin B-6 and riboflavin may lower breast cancer risk, especially in premenopausal women. Additional research is necessary to further explore these associations.
Epidemiology and Prevention Unit and.
Claudia
C
Agnoli
Epidemiology and Prevention Unit and.
Sara
S
Grioni
Epidemiology and Prevention Unit and vittorio.krogh@istitutotumori.mi.it.
Vittorio
V
Krogh
Epidemiology and Prevention Unit and.
Valeria
V
Pala
Medical Sciences Department, University of Torino, Torino, Italy; and Human Genetics Foundation, Torino, Italy.
Alessandra
A
Allione
Medical Sciences Department, University of Torino, Torino, Italy; and Human Genetics Foundation, Torino, Italy.
Giuseppe
G
Matullo
Medical Sciences Department, University of Torino, Torino, Italy; and Human Genetics Foundation, Torino, Italy.
Cornelia
C
Di Gaetano
Lombardy Cancer Registry Unit, Foundation National Cancer Institute, Scientific Institute for Care and Treatment (IRCCS), Milan, Italy;
Giovanna
G
Tagliabue
Epidemiology and Prevention Unit and.
Samuele
S
Pedraglio
Epidemiology and Prevention Unit and.
Giulia
G
Garrone
Epidemiology and Prevention Unit and.
Ilaria
I
Cancarini
Epidemiology and Prevention Unit and.
Adalberto
A
Cavalleri
Epidemiology and Prevention Unit and.
Sabina
S
Sieri
D000328:Adult; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008875:Middle Aged; D009752:Nutritional Status; D017697:Premenopause / Q000097:blood; D011446:Prospective Studies; D012256:Riboflavin / Q000097:blood*; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000097:blood*; D025101:Vitamin B 6 / Q000097:blood*
D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12; D012256:Riboflavin
B vitamins; EPIC; breast cancer; homocysteine; nested case-control study