Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and breast cancer risk in the Cancer de Màma (CAMA) study.

OBJECTIVE: We investigated the association between adherence to the recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and breast cancer (BC) risk in the Cancer de Màma (CAMA) study in a Mexican population. DESIGN: Population-based case-control study. SUBJECTS: Incident BC cases (n 1000) and controls (n 1074) matched on age, region and health-care system were recruited. SETTING: In-person interviews were conducted to assess BC risk factors and habitual diet was assessed with an FFQ. Conformity to the WCRF/AICR recommendations was evaluated through a score incorporating seven WCRF/AICR components (body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks and breast-feeding), with high scores indicating adherence to the WCRF/AICR recommendations. RESULTS: No statistically significant associations between WCRF/AICR score and risk of BC were observed. After excluding BMI from the WCRF/AICR score, the top quartile was associated with a decreased BC risk overall, with ORQ4-Q1=0.68 (95% CI 0.49, 0.92, P trend=0.03), and among postmenopausal women, with ORQ4-Q1=0.60 (95% CI 0.39, 0.94, P trend=0.03). Inverse associations were observed between BMI and risk of BC overall and among premenopausal women, with OR=0.57 (95% CI 0.42, 0.76, P trend <0.01) and 0.48 (95% CI 0.31, 0.73, P trend<0.01), respectively. Physical activity level was inversely associated with BC risk. CONCLUSIONS: The WCRF/AICR index was not related with BC risk in the CAMA study. A combination of six components excluding BMI showed strong protective associations, particularly in postmenopausal women. Further prospective studies are required to clarify the role of adherence to WCRF/AICR recommendations, particularly with respect to BMI, in the Mexican population.

Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study.

Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.

Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study.

BACKGROUND: Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship. METHODS: We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. RESULTS: Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP=0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP=0.015) and high (PARTP=0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP=0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP=0.014) and ghrelin (GHRL) (PARTP=0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP=0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women. CONCLUSIONS: Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship.