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Background: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. Methods: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990-92, baseline) and Visit 3 (1993-95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. Results: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49-0.96) but not in females (Pinteraction = 0.08). Conclusions: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. Impact: These findings support an importance of immunosurveillance in colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Nicotine metabolism is a major factor in nicotine dependence, with approximately 70% to 80% of nicotine metabolized to cotinine in Caucasians. Cotinine formation is catalyzed primarily by CYP2A6, which also converts cotinine to trans-3'-hydroxycotinine (3HC). The goal of the present study was to examine the effects of CYP2A6 deficiency on nicotine metabolism profiles in vivo and the importance of genetic variants in nicotine-metabolizing enzyme genes on urinary nicotine metabolites levels. Methods: Urine samples from 722 smokers who participated in the Singapore Chinese Health Study were analyzed using UPLC-MS/MS to detect nicotine and eight of its urinary metabolites, and a total of 58 variants in 12 genes involved in nicotine metabolism were investigated in 475 of these subjects with informative genotyping data. Results: Urine samples stratified by the ratio of 3HC/cotinine exhibited a 7-fold increase in nicotine-N'-oxide, a 6-fold increase in nicotine-Glucuronide (Gluc), and a 5-fold decrease in 3HC-Gluc when comparing the lower versus upper 3HC/cotinine ventiles. Significant (P < 0.0001) associations were observed between functional metabolizing enzyme genotypes and levels of various urinary nicotine metabolites, including CYP2A6 genotype and levels of nicotine, nicotine-Gluc, nicotine-N'-oxide and 3HC, UGT2B10 genotype and levels of cotinine, nicotine-Gluc and cotinine-Gluc, UGT2B17 genotype and levels of 3HC-Gluc, FMO3 genotype and levels of nicotine-N'-oxide, and CYP2B6 genotype and levels of nicotine-N'-oxide and 4-hydroxy-4-(3-pyridyl)-butanoic acid. Conclusions: These data suggest that several pathways are important in nicotine metabolism. Impact: Genotype differences in several nicotine-metabolizing enzyme pathways may potentially lead to differences in nicotine dependence and smoking behavior and cessation. [ABSTRACT FROM AUTHOR]

Background: We field tested new-to-market portable, digital applications to assess hearing, pulmonary, and cognitive function to determine the feasibility of implementing these applications across a range of age groups in the pilot phase of the 10,000 Families Study (10KFS), a new Minnesota family-based prospective cohort study. Methods: We followed manufacturer recommended protocols for audiometry (SHOEBOX Inc), spirometry (NuvoAir), and the digital clock drawing test (dCDT; Digital Cognition Technologies Inc). Results: These digital devices were low cost and readily implemented in a 2.5-hour health fair visit with minimal training (2-3 hours) of study staff. To date, we have performed these measurements on 197 eligible 10KFS participants during an in-person clinic visit. A total of 37 children (age 4-17 years), 107 adults (18-64 years), and 53 seniors (=65 years) were eligible to undergo hearing and pulmonary assessments. Children were less likely to successfully complete the hearing test (76%) compared with adults (86%) and seniors (89%). However, successful completion of the pulmonary assessment was high across all groups: 100% of children and seniors and 98% of adults. The dCDT was performed among those over the age of 40, and completion rates were 92% for those aged 41-64 and 94% for those =65 years. Conclusions: Our field testing indicates these digital applications are easy and cost-effective to implement in epidemiologic studies. Impact: Digital applications provide exciting opportunities to collect data in population studies. Issues related to data privacy, data access, and reproducibility of measurements need to be addressed before deploying digital applications in epidemiologic studies. [ABSTRACT FROM AUTHOR]

Background: Merkel cell polyomavirus (PyV) is causally related to Merkel cell carcinoma, a rare skin malignancy. Little is known about the serostability of other PyVs over time or associations with cutaneous squamous cell carcinoma (SCC). Methods: As part of a U.S. nested case-control study, antibody response against the PyV VP1 capsid proteins of BK and John Cunningham virus (JC) was measured using multiplex serology on 113 SCC cases and 229 gender, age, and study center-matched controls who had a prior keratinocyte cancer. Repeated serum samples from controls and both pre and postdiagnosis samples from a subset of SCC cases were also tested. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using conditional logistic regression. Results: Among controls, BK and JC seroreactivity was stable over time, with intraclass correlation coefficients of 0.86 for BK and 0.94 for JC. Among cases, there was little evidence of seroconversion following SCC diagnosis. JC seropositivity prior to diagnosis was associated with an elevated risk of SCC (OR = 2.54; 95% CI, 1.23-5.25), and SCC risk increased with increasing quartiles of JC (Ptrend = 0.004) and BK (Ptrend = 0.02) seroreactivity. Conclusions: PyV antibody levels were stable over time and following an SCC diagnosis. A history of PyV infection may be involved in the occurrence of SCC in a population at high risk for this malignancy. Impact: A single measure of PyV seroreactivity appears a reliable indicator of long-term antibody status, and PyV exposure may be a risk factor for subsequent SCC. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the effects of environmental tobacco smoke (ETS) along and combined with N-acetyltransferase (NAT2)/hepatic cytochrome P450 (CYP) 1A2 on the risk of bladder cancer among nonsmokers in Shanghai, China. Results showed a 38% increased risk of bladder cancer associated with ETS exposure. In addition, the risk increased when all ETS are combined. It was concluded that the link between ETS and cancer risk was stronger for people possessing at-risk phenotypes of CYP1A2 or NAT2.