Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
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Cancer Epidemiol. Biomarkers Prev. · Sep 2003
Val158Met Polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer.
Extensive mammographic density is heritable, strongly associated with increased breast cancer risk, and is influenced by sex hormone exposure. In a cross-sectional study of 181 pre- and 171 postmenopausal women without breast cancer, we examined the relationship of a functional polymorphism in catechol-O-methyltransferase (COMT; VAL-->MET) to mammographic density and other risk factors for breast cancer. We hypothesized that individuals who inherited the low-activity form of COMT (COMT*2 allele) would have higher levels of breast density, presumably because of reduced inactivation/detoxification of catecholestrogens. ⋯ The low-activity COMT*2 allele was also associated, after adjustment for age and ethnicity in premenopausal women, with lower serum levels of IGF-1, higher levels of FSH and progesterone, and with a larger waist:hip ratio, body mass index, and subscapular skinfold. After adjustment for body size, the associations of genotype with IGFBP-3 and FSH were no longer significant. These findings indicate that COMT genotype is associated with several risk factors for breast cancer and suggest that the low-activity COMT*2 allele is associated with a reduced risk of breast cancer among premenopausal women.
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Cancer Epidemiol. Biomarkers Prev. · Sep 2003
Comparative StudySuppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis.
Recently, we observed that dietary feeding of silibinin strongly prevents and inhibits the growth of advanced human prostate tumor xenografts in athymic nude mice without any apparent signs of toxicity together with increased secretion of insulin-like growth factor-binding protein 3 from the tumor in to mouse plasma (R. P. Singh et al., Cancer Res., 62:3063-3069, 2002). ⋯ CD31 staining for tumor vasculature showed a significant decrease (21-38%; P<0.001) in tumor microvessel density in silibinin-fed groups of tumors as compared with control group of tumors. Tumor sections were also analyzed for vascular endothelial growth factor and insulin-like growth factor-binding protein 3 protein expression, and a slightly decreased and a moderately increased cytoplasmic immunostaining in silibinin-fed groups were observed as compared with the control group, respectively. Together, these results suggest that inhibition of advanced human prostate tumor xenograft growth in athymic nude mice by silibinin is associated with its in vivo antiproliferative, proapoptotic, and antiangiogenic efficacy in prostate tumor.
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Cancer Epidemiol. Biomarkers Prev. · Jul 2003
Calcium, dairy products, and risk of prostate cancer in a prospective cohort of United States men.
Intake of calcium and/or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies. One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3), which may increase cell proliferation in the prostate. We examined the association between calcium, dairy intake, and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a prospective cohort of elderly United States adults. ⋯ Dairy intake was not associated with prostate cancer risk. The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 (RR = 1.5, 95% CI = 1.1-2.0, P trend < 0.01 for >or= 2000 mg/day of total calcium; RR = 2.1, 95% CI = 1.3-3.4 >or=2000 mg/day of dietary calcium, P trend = 0.04). Our results support the hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer.
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Cancer Epidemiol. Biomarkers Prev. · Jun 2003
Multicenter Study Comparative StudyGlutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients.
Glutathione S-transferase (GST) enzymes detoxify therapeutic drugs and reactive oxidants, so GST polymorphisms may influence survival after diagnosis of cancer. We evaluated survival according to GST polymorphisms in a population-based series of lung cancer patients. The study subjects (n = 274) were men diagnosed with lung cancer from 1993 through 1996 who participated in a case control study and provided a blood sample for genotyping. ⋯ There was no association between GSTT1 or GSTP1 genotype and survival in the overall study population, nor in a subgroup of patients treated with chemotherapy (n = 130). For GSTM1, our results are consistent with a previous study, which also observed that the GSTM1-null genotype, which confers susceptibility to lung cancer, was associated with shorter survival. Future studies of lung cancer survival should take into account GSTM1 genotype as well as investigate underlying mechanisms.
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Cancer Epidemiol. Biomarkers Prev. · Apr 2003
Comparative StudyPolymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk.
XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. ⋯ When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk.