RESUMO
To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted on Korean women. The study population consisted of 171 histologically confirmed incident breast cancer cases and 171 age-matched controls with no present or previous history of cancer. PCR-RFLP was used for the GSTP1 genotyping and statistical evaluations were performed using an unconditional logistic regression model. Postmenopausal women with the GSTP1 Val allele were found to have a reduced risk of breast cancer (OR = 0.3, 95 % CI = 0.10-0.74). A significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); compared with never-drinking women with Ile/Ile genotype, ever-drinking women with the GSTP1 Val allele had almost a three-fold risk of breast cancer (OR = 2.9, 95 % CI = 1.05-7.85), whereas never-drinking women with Val allele had half this risk (OR = 0.5, 95 % CI = 0.27-0.93). Our findings suggest that the GSTP1 polymorphism influences individual susceptibility to breast cancer in the Korean women and this effect may be modified by alcohol consumption.
Assuntos
Neoplasias da Mama/genética , Glutationa Transferase/genética , Isoenzimas/genética , Polimorfismo Genético , Adulto , Idoso , Povo Asiático , Feminino , Glutationa S-Transferase pi , Humanos , Menopausa , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
We conducted a hospital-based case-control study to evaluate the association between the XbaI and PvuII restriction fragment length polymorphisms (RFLPs) in intron I of the estrogen receptor alpha (ER alpha) gene and breast cancer risk. The study population consisted of 205 histologically confirmed incident breast cancer cases and 205 age-matched controls with no present and previous history of cancer. The PvuII genotype distribution did not show any difference between cases and controls, but the adjusted odds ratio (OR) for the XbaI X allele containing genotypes was 0.4 (95% CI: 0.3-0.6) compared with the xx genotype. The decrease in the OR appeared to be more attributable to the postmenopausal women; the ORs were 0.3 (95% CI: 0.1-0.5) and 0.5 (95% CI: 0.3-0.9) for postmenopausal and premenopausal women, respectively. Our results therefore suggest that the ER alpha XbaI polymorphism modifies individual susceptibility to breast cancer in Korean women.
Assuntos
Neoplasias da Mama/genética , Polimorfismo de Fragmento de Restrição , Receptores de Estrogênio/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Receptor alfa de Estrogênio , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Menopausa , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de RiscoRESUMO
To evaluate the potential association between NAT1/NAT2 polymorphisms and breast cancer, a case-control study was conducted in Korean women (254 cases, 301 controls). NAT1 *4/*10 genotype (42%) was the most common NAT1 genotype in this Korean population. The frequencies of slow, intermediate and rapid NAT2 acetylator genotype were 16, 39 and 44% in cases and 16, 42 and 42% in controls. Neither NAT1 rapid (homozygous or heterozygous NAT1 *10) (OR=1.2, 95% CI=0.8-1.9) nor NAT2 rapid acetylator genotype (OR=1.2, 95% CI=0.8-1.7) showed significant association with breast cancer risk. Although the risk of NAT2 rapid acetylator genotype in postmenopausal women (OR=1.4, 95% CI=0.7-2.8) was higher than that in premenopausal women (OR=1.1, 95% CI=0.7-1.7), those were not statistically significant. However, combinations of NAT1, GSTM1 and GSTT1 genotypes showed a significant linear gene-dosage relationship with breast cancer (p for trend=0.04) and those women with NAT2 rapid acetylator and both GSTM1 and GSTT1 null genotypes were at the elevated risk (OR=3.1, 95% CI=1.0-9.1). These results suggest that genetic polymorphisms of NAT1 and NAT2 have no independent effect on breast cancer risk, but they modulate breast cancer risk in the presence of GSTM1 and GSTT1 null genotypes.
Assuntos
Acetiltransferases/genética , Arilamina N-Acetiltransferase/genética , Neoplasias da Mama/genética , Glutationa Transferase/genética , Estudos de Casos e Controles , Feminino , Humanos , Isoenzimas , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
To evaluate the potential association between breast cancer risk and Ser326Cys polymorphism of hOGG1 gene, encoding for an enzyme involved in the base excision repair of 8-hydroxyguanine, hospital based case-control studies were conducted in two Asian populations consisting of 475 breast cancer cases (271 Korean and 204 Japanese) and 500 controls (314 Korean and 186 Japanese). PCR-based methods were employed for the genotyping analyses and the statistical evaluations were performed by unconditional logistic regression model. The frequency of hOGG1 Ser/Ser, Ser/Cys, and Cys/Cys genotypes were 22.5, 48.7, and 28.8% in all cases, and 23.7, 52.1, and 24.1% in the controls. No statistically significant associations between the genotypes and breast cancer risk were observed, neither when the ethnic groups were examined separately nor when the total study population was included. Neither did stratification by menopausal status reveal any association between hOGG1 genotypes and breast cancer. Our novel findings therefore suggest that hOGG1 Ser326Cys polymorphism is unlikely to play a modifying role in individual susceptibility to breast cancer among Asian women.
Assuntos
Povo Asiático/genética , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , DNA Glicosilases/genética , DNA de Neoplasias/genética , Polimorfismo Genético , Adulto , Idoso , Substituição de Aminoácidos , Estudos de Casos e Controles , Cisteína/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Japão/epidemiologia , Coreia (Geográfico)/epidemiologia , Modelos Logísticos , Pessoa de Meia-Idade , Fatores de Risco , Serina/genéticaRESUMO
We conducted a hospital-based case-control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P < or = 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.
Assuntos
Neoplasias da Mama/genética , Glutationa Transferase/genética , Polimorfismo Genético/genética , Reprodução/genética , Estudos de Casos e Controles , Climatério/genética , Feminino , Humanos , Paridade/genética , RiscoRESUMO
OBJECTIVE: We examined the potential association between alcohol consumption and genetic polymorphisms in the alcohol metabolizing enzymes, CYP2E1 and ALDH2, in individual susceptibility to breast cancer in a Korean study population. METHODS: Three hundred and forty-six histologically confirmed breast cancer patients and 377 controls with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 1995-2001. The CYP2E1 RsaI polymorphism was determined by a real time PCR method, and the ALDH2 Glu487 Lys polymorphism was determined by a PCR method with confronting two-pair primers (PCR-CTPP). RESULTS: The drinking women had a 1.4-fold risk for breast cancer (95% CI = 0.99-2.11) compared to never drinkers after adjustment for age and family history of breast cancer. No statistically significant overall differences were seen in the genotype frequencies between breast cancer cases and controls. However, the "ever"-drinking women with the CYP2E1 c2 allele containing genotypes had a 1.9-fold risk (95% CI = 0.99-3.83) for developing breast cancer compared to non-drinkers with the CYP2E1 c1/c1 genotype (P for interaction = 0.043). CONCLUSION: This study therefore suggests that the CYP2E1 c2 allele may influence the individual susceptibility to breast cancer in alcohol-consuming women.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Aldeído Desidrogenase/genética , Neoplasias da Mama/genética , Citocromo P-450 CYP2E1/genética , Polimorfismo Genético , Adulto , Consumo de Bebidas Alcoólicas/metabolismo , Aldeído-Desidrogenase Mitocondrial , Alelos , Neoplasias da Mama/enzimologia , Estudos de Casos e Controles , Primers do DNA/química , Progressão da Doença , Etanol/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Mapeamento por Restrição , Fatores de RiscoAssuntos
Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Neoplasias da Mama/enzimologia , Estudos de Casos e Controles , Códon , Reparo do DNA/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Breast cancer ranks second or third to uterine cervix cancer and stomach cancer as a cause of death in women, and as a common site of primary cancer. The large difference in its incidence between Westernized and non-Westernized countries is remarkable. There is a linear increase with age that is observed in Western countries, which are high-incidence areas, on the contrary to the inverted V shape curve seen in Asian countries. Epidemiologic studies conducted in Korea have shown that an older age, a family history of breast cancer, early menarche, late menopause, late full-term pregnancy, and never having had a breast-fed child are primary risk factors in the development of breast cancer. The estrogen-augmented-by-progesterone hypothesis explains the roles of these factors to some extent. On the other hand, recent molecular studies have revealed the existence of novel gene environmental interactions. Epidemiological features suggest that the breast cancer incidence rate in Korea will increase, but the age specific curve would not be changed in keeping with what is observed in Western countries. Strategies aimed at controlling breast cancer that include the screening guidelines and the identification of individual predispositions may give us further insights into both the etiology and the prevention of breast cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted in South Korea. MATERIALS AND METGODS: The study population consisted of 171 histologically confirmed incidents of breast cancer cases, and 171 age-matched controls with no present, or previous, history of cancer. A PCR method was used for the genotyping analyses, and statistical evaluation was performed by an unconditional logistic regression model. RESULTS: No association was observed in the study subjects, or the premenopausal women group with GSTP1 Val allele. However, postmenopausal women with GSTP1 Val allele had a reduced risk of breast cancer (OR=0.3, 95% CI=0.1~0.7). When the data were stratified, by the known risk factors of breast cancer, a significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); women with GSTP1 Val allele, that drank regularly, had a 3.0-fold increased risk of breast cancer (95% CI=1.1~7.9), whereas women with GSTP1 Val allele, that never drink, had protective effects (OR=0.4, 95% CI=0.2~0.8). CONCLUSION: Our findings suggest that GSTP1 Ile105Val polymorphism influences the individual susceptibility to breast cancer, and that this effect may be modified by alcohol consumption.
