Association of dietary intake of n-3 polyunsaturated fatty acids with breast cancer risk in pre- and postmenopausal Chinese women.

OBJECTIVE: This study aimed to evaluate the associations between breast cancer risk and intake of n-3 polyunsaturated fatty acids (PUFAs) and/or n-3 PUFA subclasses in Chinese women, and determine whether these associations varied with menopausal status or clinical characteristics. METHODS: A hospital-based case-control study including 1,589 cases and 1,621 age-frequency-matched controls was conducted. Dietary data were assessed by a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals were obtained using multiple unconditional logistic regression models after controlling for potential confounders. RESULTS: Higher intake of marine n-3 PUFAs and total n-3 PUFAs was associated with lower risk of breast cancer, with adjusted OR quartile 4 v.1 (95% confidence intervals) of 0.68 (0.55-0.84) and 0.56 (0.42-0.75), respectively. Dietary a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid were also inversely associated with breast cancer risk, with adjusted ORs (95% confidence intervals) of 0.51 (0.38-0.70), 0.68 (0.55-0.84), 0.68 (0.55-0.85), and 0.76 (0.61-0.94), respectively. In stratified analyses, these inverse associations between risk and dietary n-3 PUFAs were more evident among premenopausal women and women with ER+, PR+ and ER+PR+ tumors. A decreased risk of breast cancer was significantly associated with increasing n-3 PUFA intake in obese/overweight women, but not in women of normal weight. There was a significant interaction between linoleic acid and marine n-3 PUFAs. CONCLUSIONS: High intake of n-3 PUFAs and n-3 PUFA subtypes was associated with a lower risk of breast cancer, especially among premenopausal women and women with ER+ and/or PR+ subtype breast cancer.

Iron intake with the risk of breast cancer among Chinese women: a case-control study.

OBJECTIVE: The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women. DESIGN: Case-control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk. SETTING: A case-control study of women at three major hospitals in Guangzhou, China. PARTICIPANTS: From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited. RESULTS: In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer. CONCLUSION: Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.

Serum isoflavones and lignans and odds of breast cancer in pre- and postmenopausal Chinese women.

OBJECTIVE: Isoflavones and lignans are phytoestrogens present in plant-based foods, which have a potential preventive effect on breast carcinogenesis. The effects of phytoestrogens on breast cancer may differ according to the hormonal environment. This case-control study aimed to investigate the association between serum phytoestrogens and odds of breast cancer among Chinese pre- and postmenopausal women. METHODS: A total of 792 cases and 813 age-matched controls were included. Serum isoflavone (daidzein, genistein, glycitein, equol, and formononetin) and lignan (enterodiol and enterolactone) concentrations were measured using a liquid chromatography-tandem mass spectrometry method. RESULTS: Significant inverse associations were found between serum total soy isoflavone precursors, daidzein, genistein, formononetin, total lignans, enterodiol, enterolactone, and the odds of breast cancer in premenopausal but not postmenopausal women. For premenopausal women, the adjusted odds ratios (95% confidence intervals) for the highest versus the lowest serum concentration groups were 0.60 (0.41-0.87) for total soy isoflavones precursors, 0.64 (0.44-0.93) for daidzein, 0.62 (0.43-0.90) for genistein, 0.49 (0.35-0.68) for formononetin, 0.38 (0.25-0.57) for total lignans, 0.49 (0.33-0.73) for enterodiol, and 0.49 (0.33-0.74) for enterolactone. However, the interaction between serum phytoestrogens and menopausal status on odds of breast cancer was statistically significant only for daidzein. No significant association was found between serum equol or gycitein and the odds of breast cancer among either pre- or postmenopausal women. CONCLUSIONS: Higher levels of certain serum isoflavones and lignans were associated with reduced odds of breast cancer in premenopausal women, but the interaction was statistically significant only for daidzein.

Associations between serum concentration of flavonoids and breast cancer risk among Chinese women.

PURPOSE: In vitro and in vivo studies suggested that flavonols, flavones, flavanones and flavan-3-ols have preventive effects on breast carcinogenesis. Epidemiological evidence about the associations between these flavonoid biomarkers and breast cancer risk is limited. This study aimed to investigate the association between serum concentration of these flavonoids and breast cancer risk among Chinese women. METHODS: This hospital-based case-control study recruited 792 breast cancer cases and 813 age frequency-matched (5-year interval) controls who provided eligible blood samples in Guangdong Province, China. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure flavonoids. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI). RESULTS: Higher concentrations of serum flavonols, isorhamnetin, kaempferol, flavanones and naringenin were significantly associated with lower breast cancer risk, with adjusted ORs (95% CIs) for the highest versus the lowest group of 0.66 (0.49-0.89) for flavonols, 0.52 (0.38-0.70) for isorhamnetin, 0.60 (0.45-0.80) for kaempferol, 0.65 (0.49-0.87) for flavanones and 0.45 (0.34-0.60) for naringenin, respectively. Significant positive associations were observed between serum flavan-3-ols, epigallocatechin, epigallocatechin-3-gallate and breast cancer risk. No significant associations were observed for serum quercetin, flavones, apigenin, luteolin, hesperetin, catechin, epicatechin and epicatechin-3-gallate with overall breast cancer risk. CONCLUSIONS: This study suggested that serum flavonols and flavanones were inversely associated with breast cancer risk and serum flavan-3-ols were positively associated with breast cancer risk. Serum flavones were not associated with overall breast cancer risk. These findings warrant further confirmation in prospective studies.

Intake of total cruciferous vegetable and its contents of glucosinolates and isothiocyanates, glutathione S-transferases polymorphisms and breast cancer risk: a case-control study in China.

Cruciferous vegetables contain high levels of glucosinolates (GSL) and isothiocyanates (ITC). ITC are known to induce glutathione S-transferases (GST) and thus exert their anticarcinogenic effects. This study explored the combined effects of cruciferous vegetable, GSL and ITC intake and GST polymorphisms on breast cancer risk. A total of 737 breast cancer cases and 756 controls were recruited into this case-control study. OR and 95 % CI were assessed by multivariable logistic regression. Higher cruciferous vegetable, GSL and ITC intakes were inversely associated with breast cancer risk, with adjusted OR of 0·48 (95 % CI 0·35, 0·65), 0·54 (95 % CI 0·40, 0·74) and 0·62 (95 % CI 0·45, 0·84), respectively. Compared with women carrying the GSTP1 rs1695 wild AA genotype and high cruciferous vegetable, GSL or ITC intake, carriers of the AA genotype with low cruciferous vegetable, GSL and ITC intake had greater risk of breast cancer, with adjusted OR of 1·43 (95 % CI 1·01, 1·87), 1·34 (95 % CI 1·02, 1·75) and 1·37 (95 % CI 1·05, 1·80), respectively. Persons with the GSTM1-null genotype and lower intake of cruciferous vegetables, GSL and ITC had higher risk of breast cancer than those with the GSTM1-present genotype and higher intake, with OR of 1·42 (95 % CI 1·04, 1·95), 1·43 (95 % CI 1·05, 1·96) and 1·45 (95 % CI 1·06, 1·98), respectively. Among women possessing the GSTT1-present genotype, low intake of cruciferous vegetables, GSL or ITC was associated with higher risk of breast cancer. But these interactions were non-significant. This study indicated that there were no significant interactions between cruciferous vegetable, GSL or ITC intake and GST polymorphisms on breast cancer risk.

Association between flavonoids, flavonoid subclasses intake and breast cancer risk: a case-control study in China.

Anti-tumor effect of dietary flavonoids has been sustained by laboratory experiments, but epidemiological studies with breast cancer risk remained inconsistent and insufficient. This study aimed to investigate the associations between total and subclasses of flavonoid and breast cancer risk among Chinese population. This case-control study recruited 1522 eligible breast cancer cases and 1547 frequency-matched control subjects from June 2007 to July 2018 in Guangdong, China. Dietary intake was obtained by face-to-face interview using a validated food frequency questionnaire. Odds ratios and 95% confidence intervals were calculated by multivariable logistic regression models. After adjusting for potential confounders, inverse associations were observed between total flavonoids, anthocyanidins, proanthocyanidins, flavanones, flavones, flavonols and isoflavones and overall breast cancer risk. Comparing the highest versus the lowest quartile, odds ratio (95% confidence interval) was 0.66 (0.54-0.82) for total flavonoids, 0.61 (0.49-0.75) for anthocyanidins, 0.67 (0.54-0.83) for proanthocyanidins, 0.71 (0.57-0.88) for flavanones, 0.48 (0.39-0.60) for flavones, 0.51 (0.41-0.63) for flavonols and 0.67 (0.54-0.83) for isoflavones, respectively. No significant association was found between flavanols, flavan-3-ol monomers, theaflavins and breast cancer risk. Stratified analysis by menopausal status and estrogen receptor/progesterone receptor status showed that the associations of total flavonoids, most flavonoid subclasses with breast cancer risk were generally not modified by menopausal or estrogen receptor/progesterone receptor status. This study indicates that total flavonoids and most flavonoid subclasses intakes were inversely associated with breast cancer risk.

Direct and indirect associations between dietary magnesium intake and breast cancer risk.

This study aimed to explore the effect of dietary magnesium intake on breast cancer risk both directly and indirectly via its effect on inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). This case-control study recruited 1050 case patients and 1229 control subjects. Inflammatory marker levels of 322 cases and 322 controls, randomly selected, were measured using ELISA, and data on dietary magnesium intake were collected using a food frequency questionnaire. Multivariable logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI), and path analysis was used to investigate the mediating effect. A higher magnesium intake was associated with a lower breast cancer risk (adjusted OR = 0.80, 95% CI = 0.65, 0.99). A positive association was found between the CRP level and breast cancer risk (adjusted OR = 1.43, 95% CI = 1.02-2.01). However, IL-6 was not found to be associated with breast cancer risk. Path analysis revealed that dietary magnesium affected breast cancer risk both directly and indirectly by influencing the CRP level. The results indicate that a direct negative association and an indirect association through influencing the CRP level were observed between dietary magnesium intake and breast cancer risk.

Glucosinolate and isothiocyanate intakes are inversely associated with breast cancer risk: a case-control study in China.

Although previous studies have investigated the association of cruciferous vegetable consumption with breast cancer risk, few studies focused on the association between bioactive components in cruciferous vegetables, glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This study aimed to examine the association between consumption of cruciferous vegetables and breast cancer risk according to GSL and ITC contents in a Chinese population. A total of 1485 cases and 1506 controls were recruited into this case-control study from June 2007 to March 2017. Consumption of cruciferous vegetables was assessed using a validated FFQ. Dietary GSL and ITC were computed by using two food composition databases linking GSL and ITC contents in cruciferous vegetables with responses to the FFQ. The OR and 95 % CI were assessed by unconditional logistic regression after adjusting for the potential confounders. Significant inverse associations were found between consumption of cruciferous vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the highest with the lowest quartile were 0·51 (95 % CI 0·41, 0·63) for cruciferous vegetables, 0·54 (95 % CI 0·44, 0·67) for GSL and 0·62 (95 % CI 0·50, 0·76) for ITC, respectively. These inverse associations were also observed in both premenopausal and postmenopausal women. Subgroup analysis by hormone receptor status found inverse associations between cruciferous vegetables, GSL and ITC and both hormone-receptor-positive or hormone-receptor-negative breast cancer. This study indicated that consumption of cruciferous vegetables, GSL and ITC was inversely associated with breast cancer risk among Chinese women.

A higher Dietary Inflammatory Index score is associated with a higher risk of breast cancer among Chinese women: a case-control study.

Previous studies have investigated the association between dietary inflammatory potential and the development of cancer. For breast cancer the results have been equivocal. The present study aimed to investigate whether higher Dietary Inflammatory IndexTM (DII) scores were associated with increased risk of breast cancer among Chinese women. A total of 867 cases and 824 controls were recruited into the present case-control study from September 2011 to February 2016. DII scores were computed based on baseline dietary intake assessed by a validated 81-item FFQ. The OR and 95 % CI were assessed by multivariable logistic regression after adjusting for various potential confounders. DII scores in this study ranged from -5·87 (most anti-inflammatory score) to +5·71 (most proinflammatory score). A higher DII score was associated with a higher breast cancer risk (adjusted ORquartile 4 v. 1 2·28; 95 % CI 1·71, 3·03; adjusted ORcontinuous 1·40; 95 %CI 1·25, 1·39). In stratified analyses, positive associations also were observed except for underweight women or women with either oestrogen receptor+ or progesterone receptor+ status (but not both). Results from this study indicated that higher DII scores, corresponding to more proinflammatory diets, were positively associated with breast cancer risk among Chinese women.

Serum betaine but not choline is inversely associated with breast cancer risk: a case-control study in China.

PURPOSE: Choline and betaine are important for DNA methylation and synthesis, and may affect tumor carcinogenesis. To our knowledge, no previous study has examined the association between serum choline and betaine and breast cancer risk. This study aimed to examine whether serum choline and betaine were inversely associated with breast cancer risk among Chinese women. METHODS: This hospital-based case-control study consecutively recruited 510 breast cancer cases and 518 frequency-matched (age and residence) controls, and blood samples were available for 500 cases and 500 controls. Serum choline and betaine were assayed by high-performance liquid chromatography-tandem mass spectrometry. Multiple unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: An inverse association with breast cancer risk was observed for serum betaine (fourth vs first quartile adjusted OR 0.68, 95 % CI 0.47-0.97) and for the ratio of serum betaine to choline (fourth vs first quartile adjusted OR 0.70, 95 % CI 0.48-1.00), but not for serum choline (fourth vs first quartile adjusted OR 0.80, 95 % CI 0.56-1.15). Serum betaine was inversely associated with breast cancer risk in subjects with below-median dietary folate intake (fourth vs first quartile adjusted OR 0.48, 95 % CI 0.30-0.77). CONCLUSIONS: This study suggested that serum betaine but not choline was inversely associated with breast cancer risk. This result needed to be further confirmed by the prospective studies.

Dietary choline and betaine intake, choline-metabolising genetic polymorphisms and breast cancer risk: a case-control study in China.

Choline and betaine are essential nutrients involved in one-carbon metabolism and have been hypothesised to affect breast cancer risk. Functional polymorphisms in genes encoding choline-related one-carbon metabolism enzymes, including phosphatidylethanolamine N-methyltransferase (PEMT), choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT), have important roles in choline metabolism and may thus interact with dietary choline and betaine intake to modify breast cancer risk. This study aimed to investigate the interactive effect of polymorphisms in PEMT, BHMT and CHDH genes with choline/betaine intake on breast cancer risk among Chinese women. This hospital-based case-control study consecutively recruited 570 cases with histologically confirmed breast cancer and 576 age-matched (5-year interval) controls. Choline and betaine intakes were assessed by a validated FFQ, and genotyping was conducted for PEMT rs7946, CHDH rs9001 and BHMT rs3733890. OR and 95 % CI were estimated using unconditional logistic regression. Compared with the highest quartile of choline intake, the lowest intake quartile showed a significant increased risk of breast cancer. The SNP PEMT rs7946, CHDH rs9001 and BHMT rs3733890 had no overall association with breast cancer, but a significant risk reduction was observed among postmenopausal women with AA genotype of BHMT rs3733890 (OR 0·49; 95 % CI 0·25, 0·98). Significant interactions were observed between choline intake and SNP PEMT rs7946 (P interaction=0·029) and BHMT rs3733890 (P interaction=0·006) in relation to breast cancer risk. Our results suggest that SNP PEMT rs7946 and BHMT rs3733890 may interact with choline intake on breast cancer risk.

Joint effects of folate intake and one-carbon-metabolizing genetic polymorphisms on breast cancer risk: a case-control study in China.

This study aimed to examine the joint effects of folate intake, polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTRR) and methionine synthase (MTR) genes and breast cancer risk. A case-control study of 570 consecutively recruited breast cancer cases and 576 controls was conducted in Guangzhou, China. Multifactor dimensionality reduction and logistic regression approach were used to evaluate gene-gene interaction. The covariates were chosen based on comparison of baseline characteristics of cases and controls. Folate intake was found to be inversely associated with breast cancer risk. The MTRRrs162036 GG genotype was associated with a decreased risk of breast cancer [adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20-0.85]. Compared with the wild-type group (MTRRrs162036 AA with MTRrs1805087 AA) MTRRrs162036 AA with MTRrs1805087 GA + GG was associated with a decreased risk (OR 0.70, 95% CI 0.48-1.03). With the combined MTHFRrs1801131 TT and MTHFRrs1801133 GG genotypes as a reference, MTHFRrs1801131 TT with MTHFRrs1801133 GA + AA was associated with a decreased risk (OR 0.78, 95% CI 0.57 - 1.08) and MTHFRrs1801131 GT + GG with MTHFRrs1801133 GA + AA was associated with an increased risk (OR 1.35, 95% CI 0.88-2.05). The joint impact of MTRRrs162036 and MTRrs1805087, MTHFRrs1801131 and MTHFRrs1801133, folate and MTHFRrs1801133 may contribute to breast cancer risk.

Specific serum carotenoids are inversely associated with breast cancer risk among Chinese women: a case-control study.

Previous epidemiological studies have revealed the anti-cancer effect of dietary circulating carotenoids. However, the protective role of specific individual circulating carotenoids has not been elucidated. The purpose of this study was to examine whether serum carotenoids, including α-carotene, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin, could lower the risk for breast cancer among Chinese women. A total of 521 women with breast cancer and age-matched controls (5-year interval) were selected from three teaching hospitals in Guangzhou, China. Concentrations of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin were measured using HPLC. Unconditional logistic regression models were used to calculate OR and 95% CI using quartiles defined in the control subjects. Significant inverse associations were observed between serum α-carotene, ß-carotene, lycopene, lutein/zeaxanthin and the risk for breast cancer. The multivariate OR for the highest quartile of serum concentration compared with the lowest quartile were 0·44 (95% CI 0·30, 0·65) for α-carotene, 0·27 (95% CI 0·18, 0·40) for ß-carotene, 0·41 (95% CI 0·28, 0·61) for lycopene and 0·26 (95% CI 0·17, 0·38) for lutein/zeaxanthin. However, no significant association was found between serum ß-cryptoxanthin and the risk for breast cancer. Stratified analysis by menopausal status and oestrogen receptor (ER)/progesterone receptor (PR) showed that serum α-carotene, ß-carotene, lycopene and lutein/zeaxanthin were inversely associated with breast cancer risk among premenopausal women and among all subtypes of ER or PR status. The results suggest a protective role of α-carotene, ß-carotene, lycopene and lutein/zeaxanthin, but not ß-cryptoxanthin, in breast cancer risk.

Passive Smoking and Breast Cancer Risk among Non-Smoking Women: A Case-Control Study in China.

BACKGROUND: The role of passive smoking on breast cancer risk was unclear. This study aimed to evaluate the association between passive smoking and breast cancer risk among Chinese women. METHODS/PRINCIPAL FINDINGS: A hospital-based case-control study, including 877 breast cancer cases and 890 controls, frequency-matched by age and residence, was conducted. A structured questionnaire was used to collect information on passive smoking history through face-to-face interview by trained interviewers. Unconditional logistic regression models were used to estimate the association between passive smoking and breast cancer risk. A positive association between any passive smoking exposure and breast cancer risk was observed. Compared with women who were never exposed to passive smoking, women who were ever exposed had a higher breast cancer risk, with the adjusted odds ratio (OR) and 95% confidence interval (CI) of 1.35 (1.11-1.65). Similar result was found on home passive smoking exposure and breast cancer risk, but not on workplace passive smoking exposure. Women who were ever exposed to tobacco smoke at home had a higher risk of breast cancer compared with never exposed women, with the adjusted OR (95% CI) of 1.30 (1.05-1.61). Home passive smoking exposure showed significant dose-response relationships with breast cancer risk in smoker-years, cigarettes/day and total pack-years (Ptrend=0.003, 0.006 and 0.009, respectively). An increased total smoker-years of any passive exposure significantly elevated the risk of breast cancer (Ptrend<0.001). Positive associations and dose-response relationships were found among postmenopausal women and all subtypes of estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. CONCLUSIONS: Passive smoking was associated with an increased risk of breast cancer among non-smoking Chinese women. A stronger positive association with breast cancer risk was seen mainly among postmenopausal women.

Specific carotenoid intake is inversely associated with the risk of breast cancer among Chinese women.

The protective effect of dietary carotenoid intake on the risk of breast cancer is inconclusive. Moreover, data on dietary carotenoids in relation to breast cancer in non-Western populations are scarce. The aim of the present study was to examine the association between dietary carotenoid intake and the risk of breast cancer among Chinese women. A total of 561 cases and 561 controls who were frequency matched by age (5-year interval) and residence were recruited in the present case-control study. Dietary intake information was collected by a face-to-face interview using a validated FFQ. The OR and 95 % CI were assessed by multivariate logistic regression after adjusting for various potential confounders. An inverse association was observed between the consumption of α-carotene, ß-carotene, ß-cryptoxanthin and lutein/zeaxanthin and the risk of breast cancer. The multivariate-adjusted OR for the highest quartile of intake compared with the lowest quartile of intake were 0·61 (95 % CI 0·43, 0·88) for α-carotene, 0·54 (95 % CI 0·38, 0·78) for ß-carotene, 0·38 (95 % CI 0·26, 0·52) for ß-cryptoxanthin and 0·49 (95 % CI 0·34, 0·71) for lutein/zeaxanthin. Lycopene intake was not found to be associated with the risk of breast cancer, with the adjusted OR of 0·89 (95 % CI 0·61, 1·30). These inverse associations were more evident among pre-menopausal women and women who were exposed to second-hand smoke. The protective effect of specific carotenoid intake was observed for all subtypes of hormone receptor status of breast cancer. The present study indicated that a greater intake of specific carotenoids was associated with a decreased risk of breast cancer among Chinese women residing in Guangdong.

Choline and betaine intake is inversely associated with breast cancer risk: a two-stage case-control study in China.

Few epidemiological studies have evaluated the association of choline and betaine intake with breast cancer risk and the results remain inconsistent. This study aimed to assess the relationship between dietary intake of choline and betaine and the risk of breast cancer among Chinese women. A two-stage case-control study was conducted, with 807 cases and 807 age- (5-year interval) and residence (rural/urban)-matched controls. A validated food frequency questionnaire was used to assess dietary intake by face-to-face interview. An unconditional logistic regression model was used to calculate multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI). A significant inverse association was found between dietary choline and betaine consumption and breast cancer risk. The adjusted OR for the highest quartile of intake compared with the lowest were 0.40 (95% CI = 0.28-0.57, P(trend) < 0.001) for total choline intake, 0.58 (95% CI = 0.42-0.80, P(trend) < 0.001) for betaine intake and 0.38 (0.27-0.53, P(trend) < 0.001) for choline plus betaine intake, respectively. Intakes of individual choline compouds, choline from glycerophosphocholine, phosphocholine, phosphatidylcholine, sphingomyelin and free choline were also negatively associated with breast cancer risk. The inverse association between choline intake and breast cancer risk was primarily confined to participants with low folate level (<242 g/day), with an OR (95% CI) of 0.46 (0.23-0.91) comparing the fourth quartile with the first quartile of choline intake (P(trend) = 0.005). The present study suggests that consumption of choline and betaine is inversely associated with the risk of breast cancer. The association of choline intake with breast cancer risk is probably modified by folate intake.