Interactions of Peroxisome Proliferator–Activated Receptor γ and Diet in Etiology of Colorectal Cancer

Abstract

The peroxisome proliferator -activated receptor ; (PPAR;) is one of a group of ligand-activated nuclear receptors responsible for regulation of glucose, lipid homeostasis, cell differentiation, and apoptosis. The 12 proline-to-alanine (Pro12Ala) substitution polymorphism in PPARg produces proteins with lower activity. Variation in PPARg expression in the bowel and the role of dietary fatty acids as ligands for PPAR; led investigation of whether the associations of diet with colon and rectal cancer risk were modified by PPARg genotype. Data (diet, lifestyle, and DNA) came from casecontrol studies of colon (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls) conducted in Northern California, Utah, and the Twin City, Minnesota Metropolitan area (colon cancer study only). Unconditional logistic regression models were adjusted for age at selection, body mass index, physical activity, energy intake, dietary fiber, and calcium. We found no significant interactions between macronutrient (fat, protein, and carbohydrate) and colorectal cancer. High lutein intake [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70; 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66; 95% CI, 0.49-0.89) and PA/AA PPARg genotype were associated with reduced colon cancer risk. Risk of rectal cancer was increased among those with the PA/AA PPARg genotype and a high mutagen index (OR, 1.63; 95% CI, 1.12, 2.36). Its unclear whether the alterations in risk in those with the less active phenotype for PPARg is related to activation of PPAR; by nutrients or dietary patterns acting as ligands or direct influences of these nutrients on colon and rectal cancer processes that are important with lower PPAR; activity.

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

“…As shown in Figure 2, rs1229984 of the ADH1B gene was significantly associated with CRC in the Asian and Caucasian populations (the overall OR = 1.18, 95% CI = 1.01-1.36, p = 0.03). The meta-analysis of rs1801282/P12A/34 C > G of PPARG was involved with 14 studies (Smith et al, 2001;Jiang et al, 2005;Landi et al, 2003;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Koh et al, 2006;Kuriki et al, 2006;Theodoropoulos et al, 2006;Vogel et al, 2007 ;Kury et al, 2008;Tsilidis et al, 2009;Crous-Bou et al, 2012) among 9132 CRC cases and 12,974 controls. Using the random-effect model, our result indicated that rs1801282-G contributed to the risk of CRC (the overall OR = 1.50, 95% CI = 1.14-1.97, p = 0.004) in the Asian and Caucasian populations.…”

“…Associations between six single-nucleotide polymorphisms (SNPs) of the earlier-mentioned five genes and CRC have been reported in different ethnic groups (Smith et al, 2001;Landi et al, 2003Landi et al, , 2005Krzesniak et al, 2004;Jiang et al, 2005;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Berndt et al, 2006;Huang et al, 2006;Koh et al, 2006;Kuriki et al, 2006;Matsuo et al, 2006;Moreno et al, 2006;Theodoropoulos et al, 2006;Tranah et al, 2006;Hansen et al, 2007;Kang et al, 2007;Stern et al, 2007;Vogel et al, 2007;Yin et al, 2007;Kury et al, 2008;Funke et al, 2009;Khatami et al, 2009;Tsilidis et al, 2009;Yang et al, 2009;Engin et al, 2010;Meplan et al, 2010;Loh et al, 2011;Wu et al, 2011;Crous-Bou et al, 2012;Gil et al, 2012). These six variants comprised rs12917 and rs2308321 of MGMT, rs1229984 of ADH1B, rs4880 of SOD2, rs2228001 of XPC, and rs1801282 of PPARG.…”

PPARγ polymorphisms and cancer risk: A meta-analysis involving 32,138 subjects

“…Thus, a total of 26 studies (6-12,14-21,23-33) involving 11,627 cases and 16,050 controls were ultimately analyzed for P12A, five studies (13-16,33) involving 1,819 cases and 2,642 controls for C161T. Five studies (6,15,17,28,33) sorted the data in different race or different tumor types, therefore, each group in these studies was considered separately for pooling subgroup analyses. Table I presents the main characteristics of these studies.…”

“…Among 26 publications, 24 were published in English, and two (8,12) were in Chinese. There were 11 Asians groups (8,(10)(11)(12)(14)(15)(16)19,28,33), 13 Caucasian groups (6,7,9,13,18,21,23,24,27,28,33), and 13 American groups (6,17,20,25,26,28,29,(30)(31)(32). HWE had been tested in most controls, and most of the controls were in HWE, there were five studies (17,19,23,29,32) without genotype distribution in detail.…”

“…Two PPARÁ common polymorphisms, a C➝G transition in exon B resulting in a proline to alanine exchange at amino acid position 12 (P12A) (OMIM *0002; rs1801282) and a C➝T transition at position 161 in exon 6 (C161T) (OMIM *0009; rs3856806) have been identified and found to be associated with the risk of type 2 diabetes and cardiovascular events (4,5). In recent years evidence shows that both variations may also influence individual susceptibility to several types of cancer, such as those that occur in the central nervous system (6), lung (7,8), stomach (9)(10)(11)(12), biliary tract (13), colorectum (14)(15)(16)(17)(18)(19)(20)(21)(22), bladder (23), breast (24)(25)(26)(27), ovaries (28), endometrium (29), prostate (30)(31)(32), kidney (28) and skin (33). However, the observed results of these studies were inconsistent.…”