Cytochrome P-450 (CYP) is involved in the activation and metabolism of polycyclic aromatic hydrocarbons in tobacco products. The authors evaluated the association of two polymorphisms in the CYP1A1 gene--the noncoding Msp I polymorphism in the 3'-untranslated region and the Ile462Val polymorphism in exon 7--with colon and rectal cancer. The authors used data from two incident case-control studies of colon cancer (1,026 cases and 1,185 controls) and rectal cancer (820 cases and 1,036 controls) conducted in California and Utah (1991-2002). CYP1A1 genotype was not associated with colon or rectal cancer. Having GSTM1 present, a CYP1A1 variant allele, and the rapid-acetylator NAT2 imputed phenotype was associated with increased risk of colon cancer (odds ratio = 1.7, 95% confidence interval: 1.2, 2.3). Among men, the greatest colon cancer risk was observed for having any CYP1A1 variant allele and currently smoking (odds ratio = 2.5, 95% confidence interval: 1.3, 4.8; Wald chi(2)test: p < 0.01). Assessment of GSTM1 and CYP1A1 and rectal cancer in men showed a twofold elevation in risk for more than 20 pack-years of smoking, except among those with GSTM1 present who had a variant CYP1A1 allele. These data support the association between smoking and colon and rectal cancer. Smoking may have a greater impact on colorectal cancer risk based on CYP1A1 genotype; this might further be modified by GSTM1 for rectal cancer risk.

No abstract

Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. Other than relatively rare mutations in mismatch repair genes, the causes of MSI are not generally known. The purpose of this study was to determine if dietary intake of nutrients previously reported as being associated with colon cancer relate specifically to the MSI disease pathway. Data from a population-based case-control study of adenocarcinoma of the colon were used to evaluate associations between dietary intake and MSI. Participants were between 30 and 79 years of age at time of diagnosis and included both men and women. Dietary intake data were obtained from a computerized diet history questionnaire. MSI was evaluated in several ways: by a panel of 10 tetranucleotide repeats, and by 2 mononucleotide repeats, BAT-26 and TGF␤RII. A total of 1,510 cases had valid study data and tumor DNA on which we were able to obtain MSI status. Cases with and without MSI were compared with dietary data reported by 2,410 population-based controls to determine dietary associations that may be different for these 2 subsets of cases. We compared dietary intake for cases with and without MSI to further determine associations that are specific to the MSI disease pathway. Key words: colon cancer; diet; microsatellite instability; alcohol; cigarette smokingDiet has been repeatedly implicated in the etiology of colon cancer. 1,2 Inconsistencies in observed associations across studies could stem from individual dietary components being associated with certain types of tumors and disease pathways, but not with colon cancer overall. Ability to examine diet in relationship to specific disease end points, as determined by specific mutations in tumors, should enhance our understanding of the disease process and the role of diet in that process.Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. 3,4 People with inherited mutations of mismatch repair genes develop MSI in colon tumors; causes of MSI in sporadic colon tumors are largely unknown. 5 In our previous evaluation of lifestyle factors associated with MSI we found that cigarette smoking is specifically associated with MSI tumors, whereas other factors such as physical activity, body size, and use of aspirin and non-steroidal anti-inflammatory drugs appear to be related equally to MSIϩ and MSIϪ tumors. 6 Although dietary factors, to our knowledge, have not been examined with MSI in tumors, it is reasonable to hypothesize that components of diet, especially those that may be influenced by cigarette smoking, could influence development of unstable tumors. Alcohol could lead to unstable tumors independently or in combination with cigarette smoking. 7 Dietary antioxidants may decrease risk of unstable tumors through their role in reducing oxygen free radicals generated by cigarette smoke. 8 Other dietary factors hypothesized to influence cell growth and apoptosis, such as calcium, vitamin D and glycemic index, could be hypothesized as being associated with MSI in tumors. 9 In this ...

These results confirm observations reported by others that a family history of colorectal cancer increases risk of cancer among those diagnosed at a younger age. Associations with family history are weakest for rectal cancer and strongest for proximal colonic tumors. Since several diet and lifestyle factors influence development of cancer among those with a family history of the disease, there appears to be practical approaches for individuals with a family history of colorectal cancer to reduce their cancer risk.

No abstract