RESUMEN
Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Metabolismo Energético/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Polimorfismo de Nucleótido Simple , Adulto , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Premenopausia , Medición de Riesgo , Factores de Riesgo , Estados UnidosRESUMEN
INTRODUCTION: Soluble tumor necrosis factor receptor-II (sTNF-R2), a pro-inflammatory biomarker, is associated with obesity and breast cancer (BC). The association between sTNF-R2 and risk of mortality after BC has not been studied, specifically among Hispanic women, an at-risk population due to their high prevalence of obesity and poor prognosis. We examined the association between sTNF-R2 and mortality among Hispanic and non-Hispanic white (NHW) BC survivors. METHODS: A total of 397 invasive BC survivors (96 Hispanic, 301 NHW) contributed baseline interview data and blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models adjusting for clinical factors including body mass index. RESULTS: After a median follow-up time of 13 years, 133 deaths occurred. The association between high vs low levels of plasma sTNF-R2 and mortality was not statistically significant overall (HR, 1.32; 95% CI 0.89-1.98). However, when stratified the mortality risk among Hispanic women was nearly 3-fold (HR, 2.83; 95% CI 1.21-6.63), while risk among NHW women was attenuated (HR, 0.99; 95% CI 0.61-1.61) (p-interaction=0.10). CONCLUSION: Our results suggest Hispanic BC survivors with high sTNF-R2 levels may have increased risk of mortality and could inform targeted interventions to reduce inflammation and improve outcomes.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Inflamación , New Mexico/epidemiología , Obesidad , Factores de Riesgo , Población BlancaRESUMEN
BACKGROUND: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.
Asunto(s)
Lactancia Materna/etnología , Neoplasias de la Mama/etnología , Hispánicos o Latinos/estadística & datos numéricos , Paridad , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Lactancia Materna/estadística & datos numéricos , Femenino , Humanos , México/epidemiología , Persona de Mediana Edad , Embarazo , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown.Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study.Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00-1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29-2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR = 0.65 (95% CI, 0.44-0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29-0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry.Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry.Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692-701. ©2016 AACR.
Asunto(s)
Neoplasias de la Mama/etnología , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad/etnología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Hispánicos o Latinos , Humanos , México , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Estados UnidosRESUMEN
Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from 3 population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases. Percent Indigenous American (IA) ancestry was determined from 104 ancestry informative markers. The adaptive rank truncated product (ARTP) was used to determine the significance of each gene and the pathway with breast cancer risk, by menopausal status, genetic ancestry level, and estrogen receptor (ER)/progesterone receptor (PR) strata. MAP3K9 was associated with breast cancer overall (P(ARTP) = 0.02) with strongest association among women with the highest IA ancestry (P(ARTP) = 0.04). Several SNPs in MAP3K9 were associated with ER+/PR+ tumors and interacted with dietary oxidative balance score (DOBS), dietary folate, body mass index (BMI), alcohol consumption, cigarette smoking, and a history of diabetes. DUSP4 and MAPK8 interacted with calories to alter breast cancer risk; MAPK1 interacted with DOBS, dietary fiber, folate, and BMI; MAP3K2 interacted with dietary fat; and MAPK14 interacted with dietary folate and BMI. The patterns of association across diet and lifestyle factors with similar biological properties for the same SNPs within genes provide support for associations.
Asunto(s)
Neoplasias de la Mama/genética , Dieta/estadística & datos numéricos , Estilo de Vida , Proteínas Quinasas Activadas por Mitógenos/genética , Adulto , Anciano , Índice de Masa Corporal , Neoplasias de la Mama/etnología , Neoplasias de la Mama/metabolismo , Estudios de Casos y Controles , Grasas de la Dieta/metabolismo , Fibras de la Dieta/metabolismo , Fosfatasas de Especificidad Dual/genética , Ingestión de Energía/genética , Femenino , Ácido Fólico/metabolismo , Disparidades en el Estado de Salud , Humanos , MAP Quinasa Quinasa Quinasa 2 , Quinasas Quinasa Quinasa PAM/genética , Menopausia/genética , México/epidemiología , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 14 Activada por Mitógenos/genética , Proteína Quinasa 8 Activada por Mitógenos/genética , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética , Polimorfismo de Nucleótido Simple/genética , Grupos de Población/genética , Receptores de Estrógenos/sangre , Receptores de Progesterona/sangre , Sistema de Registros , Factores de Riesgo , San Francisco , Sudoeste de Estados UnidosRESUMEN
The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.
Asunto(s)
Aromatasa/genética , Neoplasias de la Mama/genética , Indígenas Norteamericanos/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Mama/metabolismo , Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , México/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Obesity is reported to be associated with poorer survival in women with breast cancer, regardless of menopausal status. Our purpose was to determine if the associations of obesity with breast cancer-specific, all-cause, and non-breast cancer mortality differ between Hispanic and non-Hispanic white (NHW) women with breast cancer. Data on lifestyle and medical history were collected for incident primary breast cancer cases (298 NHW, 279 Hispanic) in the New Mexico Women's Health Study. Mortality was ascertained through the National Death Index and New Mexico Tumor Registry over 13 years of follow-up. Adjusted Cox regression models indicated a trend towards increased risk for breast cancer-specific mortality in obese NHW women (hazard ratio [HR] 2.07; 95% confidence interval [CI] 0.98-4.35) but not in Hispanic women (HR 1.32; 95% CI 0.64-2.74). Obese NHW women had a statistically significant increased risk for all-cause mortality (HR 2.12; 95% CI 1.15-3.90) while Hispanic women did not (HR 1.23; 95% CI 0.71-2.12). Results were similar for non-breast cancer mortality: NHW (HR 2.65; 95% CI 0.90-7.81); Hispanic (HR 2.18; 95% CI 0.77-6.10). Our results suggest that obesity is associated with increased risk for breast cancer-specific mortality in NHW women; however, this association is attenuated in Hispanic women.
Asunto(s)
Neoplasias de la Mama/epidemiología , Obesidad/epidemiología , Adulto , Anciano , Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Persona de Mediana Edad , New Mexico/epidemiología , Obesidad/etnología , Factores de Riesgo , Programa de VERF , Análisis de Supervivencia , Población Blanca/estadística & datos numéricosRESUMEN
Bone morphogenetic proteins (BMP) are thought to be important in breast cancer promotion and progression. We evaluated genetic variation in BMP-related genes and breast cancer risk among Hispanic (2,111 cases, 2,597 controls) and non-Hispanic White (NHW) (1,481 cases, 1,586 controls) women who participated in the 4-Corner's Breast Cancer Study, the Mexico Breast Cancer Study and the San Francisco Bay Area Breast Cancer Study. BMP genes and their receptors evaluated include ACVR1, AVCR2A, ACVR2B, ACVRL1, BMP1, BMP2, BMP4, BMP6, BMP7, BMPR1A, BMPR1B, BMPR2, MSTN and GDF10. Additionally, 104 ancestral informative markers were assessed to discriminate between European and native American ancestry. The importance of estrogen on BMP-related associations was suggested through unique associations by menopausal status and estrogen (ER) and progesterone (PR) receptor status of tumors. After adjustment for multiple comparisons ACVR1 (8 SNPs) was modestly associated with ER+PR+ tumors [odds ratios (ORs) between 1.18 and 1.39 padj < 0.05]. ACVR1 (3 SNPs) and BMP4 (3 SNPs) were associated with ER+PR- tumors (ORs 0.59-2.07; padj < 0.05). BMPR2 was associated with ER-PR+ tumors (OR 4.20; 95% CI 1.62, 10.91; padj < 0.05) as was GDF10 (2 SNPs; ORs 3.62 and 3.85; padj < 0.05). After adjustment for multiple comparisons several SNPs remained associated with ER-PR- tumors (padj < 0.05) including ACVR1 BMP4 and GDF10 (ORs between 0.53 and 2.12). Differences in association also were observed by percentage of native ancestry and menopausal status. Results support the hypothesis that genetic variation in BMPs is associated with breast cancer in this admixed population.
Asunto(s)
Proteínas Morfogenéticas Óseas/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Disparidades en Atención de Salud , Hispánicos o Latinos , Humanos , Indígenas Norteamericanos , Menopausia , México/epidemiología , Persona de Mediana Edad , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Riesgo , San Francisco/epidemiología , Población Blanca , Adulto JovenRESUMEN
OBJECTIVE: Previous studies have shown an increased breast cancer risk associated with modest or high alcohol intake, however, few of these studies have included Hispanic women. The alcohol/breast cancer association was investigated in a New Mexico (NM) statewide bi-ethnic study. DESIGN: A population-based, case-control study. METHODS: Incident breast cancer cases (N = 712), aged 30-74 years, were ascertained by the New Mexico Tumor Registry (NMTR). Controls (N = 844) were identified by random digit dialing and were frequency-matched for ethnicity, age-group, and health planning district. Data were collected via in-person interview, which included questions regarding recent and past alcohol intake and breast cancer risk factors. RESULTS: The highest level of recent alcohol intake, compared to no intake, was associated with breast cancer risk for postmenopausal Hispanic women (odds ratio [OR] = 2.0 95%, confidence interval [CI] 0.8-5.1, 42+ grams/ week) and postmenopausal non-Hispanic White women (OR = 2.2, 95% Cl 1.0-5.0, 148+ grams/week), although estimates were unstable and statistically non-significant. Lower recent alcohol intake (< 148 grams/week) was associated with reduced risk for non-Hispanic Whites (OR = 0.49, 95% Cl 0.35-0.69). This pattern was independent of hormone-receptor status and was present for both premenopausal (OR = 0.29, 95% Cl 0.15-0.56) and postmenopausal women (OR = 0.56, 95% Cl 0.35-0.90). Results for past alcohol intake and breast cancer association did not demonstrate any trends and were non-significant. CONCLUSIONS: Alcohol intake does not appear to have a consistent or significant association with breast cancer in Hispanic women.