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Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39-12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen. 59:69-78, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Oral squamous cell carcinoma (OSCC) has the highest rate of increase among male cancers in Taiwan. An understanding of the molecular pathogenesis of this disease as well as the development of prognostic markers for the clinical management of this disease is very important. Thus, a systematic loss of heterozygosity (LOH) analysis was performed to define minimally deleted regions (MDRs) in 63 male OSCCs using 400 polymorphic microsatellite markers. For increasing reliability, genomic DNA was extracted from >90% tumor cells that had been purified by LCM, and only when a microsatellite marker provided LOH information in >30% of the OSCCs was there considered to be successful allelotyping. A correlation of the various MDRs with clinicopathological parameters and prognosis was carried out. In total, 32 MDRs were identified and ten were noted as novel. In addition, six MDRs were found to be associated with cigarette smoking. Among these markers, a loss of MDR c7r2 (7q32.2-q35) was significantly associated with poor disease-free survival (DFS) and ten MDRs were associated with allelic imbalance (AI) in tumors. Among the latter, a loss of MDR c14r1 (14q24.2-q32.12) and c11r1 (11q13.4-q25) had a synergistic effect on poor DFS and were able to reduce further the DFS rate in patients with MDR c7r2 loss. Taken together, the results generated in this study provide new insights that help with exploring the molecular mechanisms associated with OSCC tumorigenesis and cigarette smoking. They also should aid the development of potential prognostic markers for the clinical management of OSCC., (2011 Wiley-Liss, Inc.)

The association of diet, smoking/drinking and occupation with subsequent risk of fatal colorectal cancer was investigated in a cohort of 17,633 white males aged 35 and older, who completed a mail questionnaire in 1966. During the subsequent 20 years of follow-up, 120 colon cancer and 25 rectal cancer deaths were identified. Due to small numbers, no significant dose-response trends were observed in the study, but risk of colon cancer was elevated among heavy cigarette smokers (> or = 30/day; RR = 2.3, 95% CI 0.9-5.7), heavy beer drinkers (> or = 14 times/month; RR = 1.9, 95% CI 1.0-3.8) and white-collar workers (RR = 1.7, 95% CI 1.0-3.0) or crafts workers within service and trade industries (RR = 2.6, 95% CI 1.1-5.8). In addition, an increased risk was seen for those who consumed red meat more than twice a day (RR = 1.8, 95% CI 0.8-4.4). Risk patterns for cancers of the colon and rectum combined were similar to those reported for cancer of the colon, but the estimates were somewhat dampened. Our findings support previous reports that a high intake of red meat and a sedentary life-style may increase the risk of colon cancer.

Adrenal cancer is a heterogeneous group of neoplasms with unknown etiology. In search of risk factors, we conducted a case-control study based on data from the 1986 National Mortality Followback Survey, which included a questionnaire sent to the next of kin of almost 20,000 deceased adults (age > or = 25 year) in the United States. Information was obtained on a large number of items, including use of cigarettes, alcohol, oral contraceptives (OCs), height and weight and food consumption patterns. A total of 176 subjects who died of adrenal cancer (88 men and 88 women) and 352 controls (176 men and 176 women) who died of causes unrelated to smoking, drinking or OCs (for female controls) were included in the study. Although information on histologic type was not available, most cases were estimated from incidence surveys to be adrenocortical carcinoma, with a small percentage being malignant pheochromocytoma or neuroblastoma. An increased risk was associated with heavy smoking (> or = 25 cigarettes/day) among men (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.0-4.4) but not women. No clear association was seen for alcohol use, height and weight or food consumption patterns in either sex. Among women, increased risks were found for ever users of OCs (OR = 1.8, 95% CI 1.0-3.2) and especially those who used them before age 25 (OR = 2.5, 95% CI 1.2-5.5). When the analysis was restricted to subjects with spousal respondents, more pronounced risks were seen for ever users of OCs and for those who used OCs before age 25. Our findings suggest that cigarette smoking and use of OCs may increase the risk of adrenal cancer, but additional studies are needed with more detailed information on risk factors and histologic type of adrenal cancer.