Fish, n-3 polyunsaturated fatty acids and n-6 polyunsaturated fatty acids intake and breast cancer risk: The Japan Public Health Center-based prospective study

Limited and inconsistent studies exist on the association between the intake of fish, n-3 polyunsaturated fatty acids (PUFA) and n-6 PUFA and breast cancer. Fish and n-3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n-6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n-3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA)] and n-6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45-74 years from the Japan Public Health Center-based prospective study (JPHC study), and during 14.1 years of follow-up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n-3 PUFA and n-6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n-6 was positively associated with the development of ER+PR+ tumors [multivariable-adjusted HR (Q4)vs. (Q1)=2.94 (95% CI: 1.26-6.89; p(trend)=0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable-adjusted HR (Q2)vs. (Q1)=0.47 (95% CI: 0.25-0.89; p(trend) =0.47)]. While the overall association between the intake of total fish, n-3 PUFA and n-6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n-6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake. What's new? Whether dietary intake of fish, n-3 polyunsaturated fatty acids (PUFA) or n-6 PUFA impacts breast cancer risk is unclear. Here, to clarify possible associations, subanalyses of tumors based on estrogen receptor (ER) and progesterone receptor (PR) status were undertaken using data from Japanese breast cancer cohorts. For total intake of fish, n-3 PUFA and n-6 PUFA, no associations were detected. However, when analyzed separately, total n-6 intake was associated with ER+PR+ tumor development, while the inverse was true for eicosapentaenoic acid, an n-3 PUFA. Breast cancer risk associations with PUFA intake differ substantially by tumor subtype.