Subject(s)
Arylamine N-Acetyltransferase/genetics , Colorectal Neoplasms/etiology , Genetic Markers , Glutathione Transferase/genetics , Smoking/adverse effects , Arylamine N-Acetyltransferase/urine , Colorectal Neoplasms/epidemiology , Female , Humans , Isoenzymes , Netherlands/epidemiology , Polymorphism, Genetic , Risk Factors , Smoking/urineABSTRACT
Variants in the metabolic genes NAT1, NAT2, GSTM1 or GSTT1, may cause differences in individual detoxifying capacity of possible carcinogens. We examined the cumulative effect of putative at risk genotypes on breast cancer risk and we examined the extent to which these polymorphisms modify the association between smoking and breast cancer. A case cohort study was conducted in the DOM cohort with 676 breast cancer cases and a random sample of 669 individuals. No effect of the NAT1, NAT2 or GSTM1 genotypes on breast cancer risk was observed. However, women with GSTT1 null genotype had a 30% increased breast cancer risk compared to women with GSTT1 present (RR = 1.30 (95% confidence interval (CI) 1.04-1.64)). Smoking did not influence breast cancer risk nor did genetic variations in NAT1, NAT2 or GSTM1 in combination with smoking. Compared to women who never smoked with GSTT1 present, women with GSTT1 null genotype and who formerly smoked showed an increased breast cancer risk (RR = 2.55 (95% CI 1.10-5.90)), but current smokers who smoked 20 cigarettes or more per day did not (RR = 1.06 (95% CI 0.51-2.18)). Increasing numbers of putative at risk genotypes increased breast cancer risk in a dose dependent manner (p for trend 0.01). The risk was more than doubled in women with all four risk genotypes, RR = 2.45 (95% CI 1.24-4.86), compared to women with zero putative at risk genotypes. In conclusion, the results of this study suggest that presence of three or more putative at risk genotypes increases breast cancer risk.
Subject(s)
Arylamine N-Acetyltransferase/genetics , Breast Neoplasms/genetics , Glutathione Transferase/genetics , Isoenzymes/genetics , Breast Neoplasms/enzymology , Breast Neoplasms/epidemiology , Cohort Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Middle Aged , Netherlands , Odds Ratio , Polymorphism, Genetic , Risk Factors , Smoking/adverse effectsABSTRACT
In several population-based studies in the past urine samples were collected and stored for future research. We set out to determine the reliability of using such samples for genotyping DNA markers in epidemiologic research. A source of DNA extracted from exfoliated nucleated cells in urine is provided by the DOM cohort, in which specimens were collected 15-25 years ago. We have examined the quality of the DNA in 48 of these samples by measuring the amount of DNA isolated and its ability to provide an adequate PCR template for amplicons of different lengths. MTHFR polymorphism was analyzed in 644 specimens to determine the inter- and intraobserver reproducibility. Although the DNA amount was variable, 26 to 89% of the samples, depending both on the length of the PCR amplicon and on PCR conditions, yielded a visible PCR product. The intra- and interobserver agreements were comparable (kappa 0.86 and 0.88, respectively). Our results demonstrate that frozen urine samples can be used for DNA typing studies in women after prolonged periods of storage, but with sometimes unpredictable results. Ultimately, the genotype success rate was 89.3%. Urine collection can be considered as a useful method of obtaining DNA in large cohort studies and other circumstances when blood samples cannot be obtained or have not been stored.