Colorectal cancer (CRC) is a significant cause of morbidity and mortality in developed countries, with both genetic and environmental factors contributing to the etiology and progression of the disease. Several risk factors have been identified, including positive family history, red meat intake, smoking, and alcohol intake. Protective factors include vegetables, calcium, hormone replacement therapy, folate, nonsteroidal anti-inflammatory drugs, and physical activity. The interaction between these environmental factors, in particular diet and genes, is an area of growing interest. Currently, oncogenes, tumor suppressor genes, and mismatch repair genes are believed to play an essential role in colorectal carcinogenesis. When considering the genetics of CRC, only 10% of cases are inherited and only 2-6% can be ascribed to the highly penetrant genes, such as APC, hMLH and hMSH2. Lower penetrance genes combined with a Western-style diet contribute to the majority of sporadic CRCs. The purpose of this article is to give a brief overview of the epidemiologic studies that have been conducted and present the major findings. Here, we examine the molecular events in CRC, with particular focus on the interaction between genes and environment, and review the most current research in this area.

Objective: The current study prospectively examines the intra-uterine hypothesis by comparing maternal, paternal and grandparental lineage influences on children's diet and also maternal-child aggregation patterns during pregnancy and early childhood. Design: Prenatal dietary information was available for expectant mothers, fathers and up to four grandparents through a detailed validated semi-quantitative FFQ. At 6-year follow-up, when children averaged 5 years of age, dietary information was re-collected for mothers and a subset of maternal grandmothers using the same FFQ. Child's FFQ version was used for children. Anthropometric and sociodemographic variables were also collected. Settings: Three-generation familial cohort representative of the contemporary Irish national population. Subjects: Children aged 5 years (n 567) and their parents and grandparents. Results: Associations for energy, macronutrient and fibre intakes were compared using Pearson's correlations, intra-class correlations (ICC) and linear regression models, adjusted for energy and potential confounders. Significant, moderatestrength positive correlations were observed for nutrient intakes in children's nuclear families (ICC (range) 5 0?22-0?28). The father-child associations (r (range) 5 0?13-0?20) were weaker than the mother-child associations (r (range) 5 0?14-0?33). In general, associations were stronger for maternal postnatal intake-child intake than for maternal prenatal intake-child intake, except for percentage of energy from fat (adjusted b 5 0?16, 95 % CI 0?05, 0?26; P 5 0?004), which was stronger for maternal prenatal intake, specifically in non-breast-fed children (adjusted b 5 0?28, 95 % CI 0?12, 0?44; P 5 0?001). Among all grandparents, correlations were significant only for maternal grandmother-mother pairs (r (range) 5 0?10-0?36). Significant positive ICC were observed for nutrient intakes of maternal grandmother-mother-child triads (ICC (range) 5 0?12-0?27), not found in paternal lines. Conclusions: These findings suggest that maternal-environment programming influences dietary intake.

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of gut permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

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