N-Acetyltransferases 1 and 2 (NAT1 and NAT2), both being highly polymorphic, are involved in the metabolism of aromatic and heterocyclic aromatic amines present in cigarette smoke and red meat cooked by high-temperature cooking techniques. We investigated the effect of differences in acetylation capacity, determined by NAT1 and NAT2 genotypes, on colorectal cancer risk associated with exposure to tobacco smoke or red meat consumption. In this population-based case-control study in Germany, 505 patients with incident colorectal cancer and 604 age-and sex-matched control individuals with genotyping data and detailed risk factor information were included. Genotyping of NAT1 and NAT2 genetic polymorphisms was done using a fluorescence-based melting curve analysis method. The association between genotypes, environmental exposures, and colorectal cancer risk was estimated using multivariate logistic regression. Colorectal cancer risk associated with active smoking was elevated after accumulation of 30 + packyears of smoking [odds ratio (OR), 1.4; 95% confidence interval (95% CI), 0.9-2.2] but not significantly modified by either NAT1 or NAT2 genotype. Exposure to environmental tobacco smoke was associated with an increased risk for colorectal cancer only among NAT2 fast acetylators (OR, 2.6; 95% CI, 1.1-5.9 for exposure in childhood and adulthood). Frequent consumption of red meat significantly increased colorectal cancer risk for the group comprising all NAT2 fast acetylators or carriers of the NAT1*10 allele (OR, 2.6; 95% CI, 1.1-6.1) but not among those with ''slow'' NAT1 and NAT2 genotypes. Our findings indicate that NAT1 and NAT2 genotypes may contribute jointly to individual susceptibility and that heterocyclic aromatic amines may play an important role in colorectal cancer associated with red meat and possibly also exposure to environmental tobacco smoke. (Cancer Epidemiol Biomarkers Prev 2006;15(1):99 -107)

Results: Vaccination records were available for 397 (85.4%) adoptees (mean age, 19.4 months; 65.2% girls). Most children came from Russia (41.7%), China (20.9%), and Guatemala (15.7%). Acute or chronic malnutrition was present in 5.5% and 15.4% of adoptees, respectively. Preadoptive settings were institutional (52%), com

Introduction Studies on the association between the cytochrome P450c17α gene (CYP17) 5'-untranslated region MspA1 genetic polymorphism and breast cancer risk have yielded inconsistent results. Higher levels of estrogen have been reported among young nulliparous women with the A2 allele. Therefore we assessed the impact of CYP17 genotypes on the risk of premenopausal breast cancer, with emphasis on parity.

Several procarcinogens that are present in cooked red meat and tobacco smoke are substrates for sulfotransferase 1A1 (SULT1A1). The association between environmental exposures and colorectal cancer risk may be modified by individual differences in the metabolism. Thus, we investigated the effect of a common polymorphism in the SULT1A1 gene associated with decreased enzyme activity on the susceptibility to colorectal cancer in a populationbased case-control study. Patients (505) and 604 age-and sexmatched controls provided detailed risk factor information and were genotyped for SULT1A1 G638A using a fluorescence-based melting curve analysis method. Multivariate logistic regression analysis was used to estimate colorectal cancer risk associated with environmental exposures by SULT1A1 genotype. SULT1A1 genotype was not an independent risk factor for colorectal cancer. Risk of colorectal cancer associated with frequent consumption of red meat was significantly elevated among carriers of the SULT1A1*2 allele but not increased among subjects with the SULT1A1*1/*1 genotype (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.1 and OR 1.0, 95% CI 0.5-2.1, respectively). Colorectal cancer risk associated with 301 pack-years of active smoking was higher among carriers of the SULT1A1*2 allele (OR 1.7, 95% CI 1.0-3.2) than among individuals with the SULT1A1*1/*1 genotype (OR 1.1, 95% CI 0.6-2.1). Our results do not support a main effect of SULT1A1 genotype with regard to colorectal cancer but suggest that individuals with the low activity SULT1A1*2 allele may be at higher risk following carcinogen exposure than those with the SULT1A1*1/*1 genotype. ' 2006 Wiley-Liss, Inc.Key words: SULT1A1; genetic polymorphism; colorectal cancer; tobacco; meat Sporadic colorectal cancer is considered a multifactorial disease with both environmental and genetic factors contributing to individual risk. Environmental exposures that have been associated with an increased risk of colorectal cancer include consumption of red meat and long-term cigarette smoking.1,2 Both consumption of red meat cooked at high temperatures and tobacco smoking increase exposure to several potentially carcinogenic substances such as heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds. 3,4 Sulfotransferase 1A1 (SULT1A1) is involved in the Phase IImetabolism of xenobiotics and is expressed in the liver as well as in many extrahepatic tissues including colonic mucosa.5,6 The SULT1A1-catalyzed transfer of a sulfo moiety to its substrates usually increases their water solubility and thus facilitates excretion. However, the reaction with SULT1A1 may also lead to bioactivation of certain substances.7 A common polymorphism in the human SULT1A1 gene (G638A), referred to as SULT1A1*2 allele, leads to an amino acid change (Arg 213 His) and has been associated with decreased activity of the respective allozyme. 8,9 Hence, genetically determined differences in detoxification and bioactivation of xenobiotics may alter individual exposu...