RESUMEN
It is generally believed that the initiation of breast cancer is a consequence of cumulative genetic damage leading to genetic alterations and provoking uncontrolled cellular proliferation and/or aberrant programmed cell death, or apoptosis. Reactive oxygen species have been related to the etiology of cancer as they are known to be mitogenic and therefore capable of tumor promotion. The aim of this study was to assess the role of common variation in 10 polymorphic genes coding for antioxidant defense enzymes in modulating individual susceptibility to breast cancer using a case-control study (N cases = 4,474 and N controls = 4,580). Both cases and controls were from the East Anglian region of the United Kingdom. We have identified a set of 54 single nucleotide polymorphisms (SNPs) that efficiently tag all the known SNPs in the 10 genes and are also expected to tag any unknown SNPs in each gene. We found no evidence for association of common variants in SOD1, SOD2, GPX1, GPX4, GSR, TXNRD1, and TXN2. There was borderline evidence for association of variants in CAT g27168a {P [2 degrees of freedom (df)] = 0.05}, TXN t2715c [P (2 df) = 0.007], and TXNRD2 A66S and TXNRD2 g23524a (P(trend) = 0.074 and 0.046, respectively). For TXNRD2 A66S [AS versus AA: odds ratio (OR), 1.05; 95% confidence intervals (95% CI), 0.96-1.15; SS versus AA: OR, 1.12; 95% CI, 0.98-1.29], there are bioinformatics data to suggest that it is functional but confirmation in independent data sets is required before they can be regarded as definitive breast cancer susceptibility alleles. Even if confirmed, these four alleles would account for just 0.32% of the excess familial risk of breast cancer.
Asunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Oxidorreductasas/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Estudios de Casos y Controles , Inglaterra , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Oxidorreductasas/metabolismo , Especies Reactivas de OxígenoRESUMEN
PURPOSE: Risk factors that influence the incidence of breast cancer may also affect survival after diagnosis. METHODS: Data from 4,560 women with invasive breast cancer who had taken part in the population-based Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) breast cancer study were used to investigate the influence on survival of variables related to pregnancy, menarche and menopause, prior use of exogenous hormones, height, weight, body mass index (BMI), smoking history, and alcohol intake. RESULTS: In univariate analyses, there was no association between prognosis and age at menarche and menopause, menopausal status at diagnosis, smoking history, or prior use of the oral contraceptive pill. Women whose most recent pregnancy was more than 30 years ago had a 35% reduced risk of dying (95% CI, 8% to 54%) compared with women who had a full-term pregnancy in the past 15 years, and the use of hormone replacement therapy for more than 4 years was associated with a similar risk reduction. BMI was associated with a 3% (95% CI, 1% to 4%) increase in mortality per unit increase. Improved prognosis was seen with increasing current alcohol consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit of alcohol consumed per week. CONCLUSION: The apparent benefit of alcohol intake has not been described before, and our data need to be interpreted with some caution. However, our finding that an increase in BMI is associated with a poorer prognosis supports previously published data and suggests that advice on weight loss should be given to all obese patients with breast cancer.
Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Causas de Muerte , Invasividad Neoplásica/patología , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Consumo de Bebidas Alcohólicas , Índice de Masa Corporal , Lactancia Materna , Neoplasias de la Mama/terapia , Estudios de Cohortes , Anticonceptivos Hormonales Orales , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Incidencia , Menarquia/fisiología , Menopausia/fisiología , Persona de Mediana Edad , Estadificación de Neoplasias , Paridad , Embarazo , Probabilidad , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
The BRCA2 372 HH genotype defined by the BRCA2 N372H nonconservative amino acid substitution polymorphism was recently reported to be associated with a small increased risk of breast cancer. We investigated whether this polymorphism was associated with ovarian cancer risk by conducting British and Australian case-control comparisons in parallel, including a total sample of 1,121 ovarian cancer cases and 2,643 controls. There was no difference in genotype frequency between control groups from the 2 studies (p = 0.9). The HH genotype was associated with an increased risk of ovarian cancer in both studies, and the risk estimate for the pooled studies was 1.36 (95% CI 1.04-1.77, p = 0.03). There was also a suggestion that this risk may be greater for ovarian cancers of the serous subtype for both studies, with an OR (95% CI) of 1.66 (1.17-2.54) for the 2 studies combined (p = 0.005). The BRCA2 372 HH genotype appears to be associated with an increased risk of ovarian cancer of a similar magnitude to that reported for breast cancer.