RESUMEN
PURPOSE: Increased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study. PATIENTS AND METHODS: Factor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression. RESULTS: Homozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk. CONCLUSION: Our results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.
Asunto(s)
Factores de Coagulación Sanguínea/genética , Neoplasias Colorrectales/genética , Factor V/genética , Polimorfismo Genético , Protrombina/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
Cytochrome P450 (CYP) enzymes, involved in metabolism of tobacco carcinogens, are also involved in estrogen metabolism and many are regulated by estrogens. These genes may thus be of relevance to gender-specific differences in lung cancer risk, particularly in early-onset lung cancer, where a high proportion of women is observed. We conducted a case-control study to investigate genetic polymorphisms in cytochromes that might modify the risk of developing early-onset lung cancer. In total, 638 Caucasian patients under the age of 51 with primary lung cancer and 1300 cancer-free control individuals, matched by age and sex, were included in this analysis. Thirteen polymorphisms in the CYP1A1, CYP1B1, CYP2A13, CYP3A4 and CYP3A5 genes were analyzed. No significant association was found for any of the analyzed polymorphisms and lung cancer risk overall. However, among women, a significantly increased risk of early-onset lung cancer was observed for carriers of the minor allele of CYP1B1 SNP rs1056836 [odds ratio (OR) 1.97; 95% confidence interval (CI) 1.32-2.94; P < 0.001]. Also, a non-significant increase in lung cancer risk was observed in the group of women carriers of the minor allele of CYP2A13 SNP rs1709084 (OR 1.64; 95% CI 1.00-2.70; P = 0.05). The effect of these two polymorphisms was shown to be modified by smoking. Haplotype analysis was performed for CYP1B1 and CYP2A13. No differences between cases and controls were observed for both genes (P = 0.63 and P = 0.42 for CYP1B1 and CYP2A13, respectively). Our results suggest that the CYP1B1 and the CYP2A13 genotypes may contribute to individual susceptibility to early-onset lung cancer in women.
Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/genética , Lesiones Precancerosas/genética , Adulto , Edad de Inicio , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/epidemiología , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversosRESUMEN
BACKGROUND: Breast cancer is a heterogeneous disease with subtypes that may vary in their etiologies. Menopausal hormone therapy has been associated more strongly with lobular and tubular than ductal histologic types and with tumors that are smaller, hormone receptor-positive, and of lower grade. At the same time, correlations have been observed between histology and clinical characteristics. To identify those tumor subtypes most strongly associated with hormone therapy use, it is necessary to disentangle these interrelationships. METHODS: Based on 3,464 postmenopausal breast cancer cases and 6,657 controls from the population-based Mammary carcinoma Risk factor Investigation study, we used polytomous logistic regression to evaluate associations between hormone therapy use and risk of invasive breast cancer subtypes. We assessed variations in risk for selected tumor characteristics among histologic and hormone receptor subtypes, both overall and for specific hormone therapy regimens. RESULTS: Lobular and mixed types showed less variation by prognostic factors than did ductal tumors. Current hormone therapy use had the strongest associations with prognostic variables in estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal tumors and in lobular tumors regardless of ER/PR status, with little effect on ER/PR-negative ductal tumors. The observed associations varied minimally by hormone therapy type or regimen. CONCLUSION: Current hormone therapy use was associated with more favorable breast cancer characteristics for ductal tumors but had less effect on prognostic characteristics in women with lobular tumors. Both histologic type and estrogen receptor/progesterone receptor status seem to be important in explaining the role of hormone therapy in the etiology of breast cancer subtypes.