Northeast Regional Cancer Institute

UDP-glucuronosyltransferases (UGTs) play an important role in the phase II metabolism of exogenous and endogenous compounds. As colorectal cancer (CRC) etiology is thought to involve the biotransformation of dietary factors, UGT polymorphisms may affect CRC risk by altering levels of exposure. Genotyping of over 1800 Caucasian subjects was completed to identify the role of genetic variation in nine UGT1A and five UGT2B genes on CRC risk. Unconditional logistic regression and haplotype analyses were conducted to identify associations with CRC risk and potential gene-environment interactions. UGT1A haplotype analysis found that the T-G haplotype in UGT1A10 exon 1 (block 2: rs17864678, rs10929251) decreased cancer risk for the colon [proximal (OR = 0.28, 95% CI = 0.11–0.69) and for the distal colon (OR = 0.32, 95% CI = 0.12–0.91)], and that the C-T-G haplotype in the 3′ region flanking the UGT1A shared exons (block 11: rs7578153, rs10203853, rs6728940) increased CRC risk in males (OR = 2.56, 95% CI = 1.10–5.95). A haplotype in UGT2B15 containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI = 1.21–5.04) and in females (OR = 3.08, 95% CI = 1.08–8.74). An interaction was found between high NSAID use and the A-G-T haplotype (block 10: rs6717546, rs1500482, rs7586006) in the UGT1A shared exons that decreased CRC risk. This suggests that UGT genetic variation alters CRC risk differently by anatomical sub-site and gender and that polymorphisms in the UGT1A shared exons may have a regulatory effect on gene expression that allows for the protective effect of NSAIDs on CRC risk.

Abstract The most recent consensus statement issued by the World Cancer Research Fund and the American Institute for Cancer Research concluded that the evidence to support a positive association between intake of red and processed meat and colorectal cancer was convincing, yet the evidence for specific mechanisms explaining these associations remained inconclusive. To identify responsible compounds that may account for the previously observed statistical associations between meat and colorectal cancer, the present study examined associations between red meat, processed meat, and meat-derived heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), nitrites, and nitrates and colorectal cancer in a population-based case-control study in central and northeast Pennsylvania. This population is at particularly high risk for colorectal cancer compared to the U.S. as a whole (54.5/100,000 in PA versus 48.8/100,000 in the U.S. at the start of this study in 2007). Participants (989 colorectal cancer cases and 1,033 healthy controls) completed a 137-item food frequency questionnaire, the National Cancer Institute's (NCI) Diet History Questionnaire (DHQ), which included a meat module that was linked to a database of nitrites and nitrates. The meat module also allowed for the use of NCI's Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) software application to generate estimates of HCAs and PAHs. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat variables and colorectal cancer, stratified by anatomical subsite, were estimated from unconditional logistic regression models. After multivariable adjustment, there were no associations between red or processed meat and colorectal cancer. Nitrite plus nitrate intake was positively associated with proximal colon cancer (OR = 1.54, 95% CI = 1.03-2.31, P-trend = 0.025). A positive association was observed between 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal cancer (OR = 1.36, 95% CI = 1.02-1.82, P-trend = 0.027). Total mutagenic activity was positively associated with distal colon cancer (P-trend = 0.049). There was no association between benzo[a]pyrene and total colorectal cancer or any sub-site. These results indicate that HCAs, PAHs, nitrites, and nitrates may be risk factors for colorectal cancer, but additional studies that examine risk factors stratified by anatomical subsite are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4460A. doi:1538-7445.AM2012-4460A

In 2002, 10.4% of the 10 million persons alive who have ever been diagnosed with cancer had colorectal cancer (CRC). Barriers, such as distance, terrain, access to care and cultural differences, to CRC survivorship may be especially relevant in rural communities. We tested the hypothesis that teams from rural cancer coalitions and hospitals would develop a Community Plan (CP) to enhance CRC survivorship. We used community-based participatory research and the PRECEDE-PROCEED model to train teams from rural cancer coalitions and hospitals in Pennsylvania and New York. We measured knowledge at three points in time and tested the change with McNemar's test, corrected for multiple comparisons (p < 0.0167). We also conducted a qualitative review of the CP contents. Fourteen (93.3%) of the 15 coalitions or hospitals initially recruited to the study completed a CP. Knowledge in public health, sponsorship of A National Action Plan for Cancer Survivorship, and CRC survivorship and treatment increased. Teams identified perceived barriers and community assets. All teams planned to increase awareness of community assets and almost all planned to enhance treatment-related care and psychosocial care for the CRC survivor; 50% planned to enhance primary care and CRC screening. The study demonstrated the interest and ability of rural organizations to plan to enhance CRC survivorship, including linkage of CRC survivorship to primary care. Rural cancer coalitions and hospitals may be a vehicle to develop local action for A National Action Plan. Access to more comprehensive care for CRC cancer survivors in rural communities appears to be facilitated by the community-based initiative described and investigated in this study. Efforts such as these could be replicated in other rural communities and may impact the care and quality of life of survivors with many types of cancers. While access to health services may be increased through community-based initiatives, we still need to measure the impact of such initiatives on the long term health and well being of cancer survivors in rural locations.