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Background: Heterocyclic amines (HCAs) are mutagenic compounds generated when meats are cooked at high temperature and for long duration. Evidence from animal studies has pointed towards a possible role of HCAs in breast carcinogenesis. However, findings from previous studies on HCAs and breast cancer are inconsistent, possibly due to genetic variations in the enzymes metabolizing HCAs. Methods: To evaluate whether the associations of intakes of estimated HCAs, meat-derived mutagenicity (MDM), and red meat with risk of postmenopausal breast cancer were modified by N-acetyltransferase 2 (NAT 2) acetylator genotype or cytochrome P450 1A2 −164 A/C (CYP1A2) polymorphism, we conducted a nested case-control study with 579 cases and 981 controls within a prospective cohort, the Nurses' Health Study (NHS). HCAs and MDM intakes were derived using a cooking method questionnaire administered in 1996. Results: NAT2 acetylator genotype, the CYP1A2 polymorphism, and intakes of HCAs, MDM, and red meat were not associated with risk of postmenopausal breast cancer. There was also no interaction between NAT2 acetylator genotype and HCAs and MDM and red meat intake in relation to breast cancer. There was no interaction between the CYP1A2 genotype and HCAs and MDM and red meat intake in relation to breast cancer. Conclusion: These results do not support the hypothesis that genetic polymorphisms of xenobiotic enzymes involved in the metabolism of HCAs may modify the associations between intakes of red meat or meat-related mutagens and risk of breast cancer. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B110.

Aromatic and heterocyclic amines are carcinogens in tobacco smoke that cause mammary tumors in rodents. N-acetyltransferase 2 (NAT2) can detoxy aromatic amines and polymorphisms in the NAT2 gene result in slow, intermediate and rapid acetylation phenotypes. Slow NAT2 acetylation has been hypothesized to potentiate the risk of smoking for both breast and bladder cancer. Whereas this hypothesis is reasonably well-established for bladder cancer, the data for breast cancer are still being evaluated, most recently in a meta-analysis of up to 13 studies. In a subset of these studies including 4,264 cases, a ∼1.4 fold increase in risk of breast cancer was observed among women exposed to more than 20 pack-years of cigarette smoking. This increase in risk was confined to slow acetylators, and no statistically significant increase in risk was observed among rapid acetylators. We sought to replicate this finding in a consortium of six large prospective cohorts in the United States and Europe. We genotyped the three most common polymorphisms that define NAT2 acetylation phenotype in populations of European origin among approximately 7,750 breast cancer cases and 9,900 matched controls with prospectively collected information on tobacco smoking and established risk factors for breast cancer. Nested case-control analyses showed no association between NAT2 acetylation phenotype (rapid, intermediate, slow) and breast cancer risk. Furthermore, no interaction was observed between smoking status (specifically never, former or current) and NAT2 acetylation phenotype on breast cancer risk (likelihood ratio test p-interaction 0.58). Ongoing analyses are examining more detailed measures of cigarette smoking such as duration, intensity, pack years, and smoking during the potentially critical period between menarche and first full term pregnancy, as well as subsets of patients defined by menopausal or steroid hormone receptor status. These data contribute substantially to resolving the longstanding debate over whether smoking affects breast cancer risk particularly in women with limited capacity to acetylate tobacco carcinogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-408.

Introduction Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer.

This American Association for Cancer Research Special Conference brought together scientists with diverse expertise to address issues related to use of appropriate epidemiological, statistical, and laboratory methods to study the genetic epidemiology of cancer. Discussions focused on experiences with association studies using single nucleotide polymorphisms and haplotypes, their limitations, and what is needed to improve on the current 'state of the art'. Various studies were presented in different contexts, ranging from candidate gene studies to whole genome scans, and conducted in prospective cohorts, case–control studies, and other study designs. Common problems such as determining the probability that observed associations are false negative or false positive, the potential effects of admixture, and determining which polymorphisms to examine in which genes and in which populations were examined. Problems specific to haplotype analysis were discussed, with emphasis on haplotype block structures and on how to use haplotypes in analysis. Questions were also posed as to determining the functional relevance of single nucleotide polymorphisms in molecular epidemiology. Finally, future directions, using specific examples, were addressed.

Background APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations. Methods We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study. Results Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03). Conclusions These results suggest a beneficial effect of polymorphism rs429358 in the oldest men. Electronic supplementary material The online version of this article (doi:10.1186/s12888-014-0223-x) contains supplementary material, which is available to authorized users.

This paper attempts to measure the impact on Canada of a Canada-United States 'sectoral free trade arrangement' involving five manufacturing sectors. The analysis is based on a quantitative general equilibrium model, with particular focus on the technology, industrial structure, and conduct within the manufacturing industries in Canada. The results of the paper indicate that there are surprisingly large benefits to a sectoral free trade agreement. While the real income gains are much smaller than with a bilateral free trade arrangement involving all industrial sectors, they are on the order of 37 per cent of value added in the sectors considered. Une evaluation quantitative de l'impact economique sur le Canada d'un libre-echange sectoriel avec les Etats-Unis. Ce memoire tente de mesurer l'impact sur le Canada d'un accord de libre-echange sectoriel Canada-Etats-Unis impliquant cinq secteurs manufacturiers. L'analyse est fondee sur un modele d'equilibre general quantitatif et met l'accent sur la technologie, ainsi que sur la structure et les comportements industriels intra-sectoriels dans les industries manufacturieres au Canada. Les resultats de cette analyse montrent que des benefices etonnamment importants peuvent emaner d'un accord de libre-echange sectoriel. M8me si les accroissements de revenu sont bien plus faibles que ceux qui seraient engendres par un accord de libre-echange bilateral impliquant tous les secteurs industriels, ils atteignent un ordre de grandeur de 37% de la valeur ajoutee dans les secteurs impliques.