UGT1A6 and UGT2B15 polymorphisms and acetaminophen conjugation in response to a randomized, controlled diet of select fruits and vegetables.

Acetaminophen (APAP) glucuronidation is thought to occur mainly by UDP-glucuronosyltransferases (UGT) in the UGT1A family. Interindividual variation in APAP glucuronidation is attributed in part to polymorphisms in UGT1As. However, evidence suggests that UGT2B15 may also be important. We evaluated, in a controlled feeding trial, whether APAP conjugation differed by UGT1A6 and UGT2B15 genotypes and whether supplementation of known dietary inducers of UGT (crucifers, soy, and citrus) modulated APAP glucuronidation compared with a diet devoid of fruits and vegetables (F&V). Healthy adults (n = 66) received 1000 mg of APAP orally on days 7 and 14 of each 2-week feeding period and collected saliva and urine over 12 h. Urinary recovery of the percentage of the APAP dose as free APAP was higher (P = 0.02), and the percentage as APAP glucuronide (APAPG) was lower (P = 0.004) in women. The percentage of APAP was higher among UGT1A6*1/*1 genotypes, relative to *1/*2 and *2/*2 genotypes (P = 0.045). For UGT2B15, the percentage of APAPG decreased (P < 0.0001) and that of APAP sulfate increased (P = 0.002) in an allelic dose-dependent manner across genotypes from *1/*1 to *2/*2. There was a significant diet × UGT2B15 genotype interaction for the APAPG ratio (APAPG/total metabolites × 100) (P = 0.03), with *1/*1 genotypes having an approximately 2-fold higher F&V to basal diet difference in response compared with *1/*2 and *2/*2 genotypes. Salivary APAP maximum concentration (C(max)) was significantly higher in women (P = 0.0003), with F&V (P = 0.003), and among UGT1A6*2/*2 and UGT2B15*1/*2 genotypes (P = 0.02 and 0.002, respectively). APAP half-life was longer in UGT2B15*2/*2 genotypes with F&V (P = 0.009). APAP glucuronidation was significantly influenced by the UGT2B15*2 polymorphism, supporting a role in vivo for UGT2B15 in APAP glucuronidation, whereas the contribution of UGT1A6*2 was modest. Selected F&V known to affect UGT activity led to greater glucuronidation and less sulfation.

Opportunistic Screening of Oral Potentially Malignant Disorders: A Public Health Need for India.

PURPOSE: Oral cancer (OC) is the leading cancer in 25% of Indian cancer registries, and 80% of OCs are diagnosed in advanced stages. OC screening is a topic of debate. Studies from other countries have used a variety of study designs as OC screening strategies. There are not many studies from India on strategic screening, and there is a need to review the literature to provide insights and knowledge about screening programs. The purpose of this narrative review is to present broad epidemiologic evidence on the OC burden in India, to discuss and summarize the currently available evidence for OC screening strategies, and to highlight a feasible opportunistic screening strategy for addressing OC burden in India. METHODS: Medline and EMBASE were used to identify articles. Data from GLOBOCAN and government reports were obtained from websites. As many key concepts and divergent views cannot be addressed with a single research question, a narrative review was considered appropriate, but to ensure a comprehensive literature search, a systematic review search strategy was used. RESULTS: OC rates are rising more rapidly in India than projected. Wide variations in OC incidence within India reflect regional diversity of risk factors. Studies abroad have demonstrated the feasibility of opportunistic screening of oral potentially malignant disorders by dentists; however, although recommendations exist in India, no studies of opportunistic screening by dentists have been reported. CONCLUSION: The projected major increases in the OC burden necessitate an OC screening program; opportunistic screening of high-risk groups by dentists using oral visual examination is recommended as a cost-effective strategy. As a way forward, a pilot project to assess the feasibility of regional opportunistic screening is in progress.

Buccal cell DNA yield, quality, and collection costs: comparison of methods for large-scale studies.

There is considerable interest in noninvasive and cost-effective methods for obtaining DNA in large-scale studies. In this randomized crossover study of 22 participants, we compared the DNA yield, quality, and associated costs of buccal cell DNA collected using cytobrushes (three brushes per collection) and swish (i.e., mouthwash) in self-administered procedures. There was a nonstatistically significant higher yield from the mouthwash compared with cytobrush collections (15.8 microg versus 12.0 microg, respectively; P = 0.53). PCR reactions that required short (0.3 kb) or intermediate (1.1 kb) DNA fragments were 100% successful for DNA from brush and mouthwash, whereas PCRs for reactions that required long fragments (7.8 kb) failed for all of the participants from cytobrush DNA and were 81% successful for DNA from the mouthwash source. The brush collections provided sufficient DNA for an estimated 150-225 PCR reactions requiring short and intermediate DNA fragments. The estimated per person costs for buccal brush DNA collections in large studies were less then half (8.50 dollars) those for the mouthwash method (18 dollars). In addition, we tested whether cytobrush instructions to rub cheeks before collection or collect cells only in the morning increased DNA yield and whether repeat brushings of the same cheek reduced DNA yield. These variations resulted in no significant differences in DNA yields. We conclude that the collection of DNA with cytobrushes using simple instructions is cost effective in large-scale studies, and yields sufficient quantity and quality of DNA for genotyping.