Nutrient pathways and breast cancer risk: the Long Island Breast Cancer Study Project.

The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we used interview data from a population-based sample of 1463 breast cancer cases and 1500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was used to account for biologically plausible nutrient pathways (1-carbon metabolism, oxidative stress, glycemic control, and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the 1-carbon metabolism, oxidative stress, and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer.

Intake of antioxidant nutrients and risk of non-Hodgkin's Lymphoma in the Women's Health Initiative.

Incidence rates of non-Hodgkin's lymphoma (NHL) increased substantially in the United States and worldwide during the latter part of the 20(th) century, but little is known about the etiology of this condition. Antioxidant nutrients may reduce the risk of NHL by quenching free radicals, which may contribute to carcinogenesis by damaging DNA and lipid membranes. We examined the association of intake of vitamin A and antioxidant nutrients with risk of NHL and its major subtypes in 1,104 cases of NHL identified among 154,363 postmenopausal women followed for an average of 11 yr in the Women's Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Of all nutrients examined, only total vitamin A intake (from diet and supplements combined) was inversely associated with risk of NHL overall (multivariate adjusted HR for highest vs. lowest quartile 0.83, 95% CI 0.69-0.99), whereas total vitamin C intake was inversely associated with risk of diffuse large B-cell lymphoma (HR for highest vs. lowest quartile 0.69, 95% CI 0.49-0.98). Overall, this study provides some evidence of inverse associations of intake of total vitamin A and total vitamin C with the risk of NHL and diffuse lymphoma, respectively.

Fruits, vegetables, and micronutrient intake in relation to breast cancer survival.

OBJECTIVE: To determine whether fruit, vegetable, and micronutrient intake 1 year prior to breast cancer diagnosis is associated with a reduction in the subsequent risk of all-cause or breast cancer-specific mortality. METHODS: Follow-up data from 1,235 invasive breast cancer cases age 25-98 years from the Long Island Breast Cancer Study Project were analyzed. At the 1996-1997 case-control interview, respondents completed a food frequency questionnaire, which assessed dietary intake of fruits, vegetables, and vitamin supplement use in the previous 12 months. All-cause mortality (n=186 deaths) and breast cancer-specific mortality status (n=125 deaths, 67.2%) were determined through December 31, 2002. RESULTS: Hazard ratios (HRs) for all-cause mortality were insignificantly reduced for intake of any fruits, fruit juices, and vegetables (HR=0.68, 95% CI: 0.42-1.09) and leafy vegetables (HR=0.72, 95% CI: 0.41-1.24) among post-menopausal women only. Both of these associations were more pronounced among those with ER+PR+ tumors (HR=0.54, 95% CI: 0.27-1.10, and HR=0.66, 95% CI: 0.33-1.31, respectively). Similar associations were observed for breast cancer-specific mortality. CONCLUSIONS: In a cohort of women diagnosed with breast cancer, higher intake of fruits, vegetables, and micronutrients was associated with a non-significant survival advantage in post-menopausal women only.

One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer.

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.

Fruits, vegetables, and micronutrients in relation to breast cancer modified by menopause and hormone receptor status.

Whether fruit, vegetable, and antioxidant micronutrient consumption is associated with a reduction in breast cancer incidence remains unresolved. To address this issue, we analyzed data from a large population-based case-control study, with consideration given to whether the associations varied with menopausal status or with clinical characteristics of the cases' disease. Study participants completed a modified Block food frequency questionnaire, which included assessment of the frequency and portion sizes of 13 fruits and fruit juices and 16 vegetables and the use of multiple and single vitamin supplements. Statistical analyses were done on 1,463 cases and 1,500 controls. Among postmenopausal women, reduced odds ratios [OR; 95% confidence intervals (95% CI)] were noted for the highest fifth, as compared with the lowest fifth, of intake of any vegetables [0.63 (0.46-0.86); P for trend < 0.01] and leafy vegetables [0.66 (0.50-0.86); P for trend = 0.03] after controlling for age and energy intake. Adjusted ORs (95% CIs) were also decreased for postmenopausal breast cancer in relation to high intake of carotenoids, alpha-carotene, beta-carotene, lutein, and particularly lycopene [0.66 (0.48-0.90); P for trend = 0.03]. Inverse associations for fruits and vegetables were stronger for postmenopausal women with estrogen receptor (ER)+ tumors (OR, 0.65; 95% CI, 0.51-0.82) than ER- tumors (OR, 0.92; 95% CI, 0.64-1.32), but results were less consistent for micronutrients. No similarly reduced associations were observed among premenopausal women. ORs did not appreciably differ by in situ or invasive breast cancer or by whether cases had begun chemotherapy. Our results support an inverse association for fruit and vegetable intake among postmenopausal but not premenopausal breast cancer, which may be more pronounced among women with ER+ tumors.