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Biomedical subjects

Peter G Shields

Publications and source records attributed to Peter G Shields.

44 records · Page 3Linked to original sources
PubMed2002

Molecular epidemiology of smoking and lung cancer.

Lung cancer is the single most common cause of death, and almost all of it is due to tobacco smoking. Before the widespread use of cigarettes in this century, lung cancer was a rare illness. Tobacco smoke is a complex mixture of numerous mutagens and carcinogens. Over the last 40 years, the type of cigarettes most frequently used has been changing, namely the increased use of low tar and nicotine cigarettes. This has been accompanied by an increased risk of lung cancer due to a smokers' need to maintain blood nicotine levels, which in turn causes the need for smoking more cigarettes per day and deeper inhalation. This phenomena has led to the increasing rates of lung adenocarcinoma, compared to squamous cell carcinoma. It also probably explains, in part, the greater risk of lung cancer in women compared to men (in addition to some biological differences). The study of lung cancer involves many types of biomarkers, including those that measure exposure, the biologically effective dose and harm. The use of these has allowed us to understand many parts of lung carcinogenesis. Genetic susceptibilities play a large role in lung cancer risk. They govern smoking behavior (affecting dopamine reward mechanisms due to nicotine and nicotine metabolism), carcinogen metabolism and detoxification, DNA repair, cell cycle control and other cellular responses. The need for the study of lung cancer is highlighted by the need to improve cessation rates and reduce exposure among persons who cannot quit smoking, for better prevention strategies for former smokers and an understanding of environmental tobacco smoke risk.

Carcinogens↗
PubMed2002

Tobacco smoking, harm reduction, and biomarkers.

The only known way to reduce cancer risk in smokers is complete cessation, but many smokers are unable or unwilling to quit. Consequently, tobacco companies are now marketing products that purport to reduce carcinogen exposure, with the implication that such products provide a safer way to smoke. Moreover, researchers are exploring ways to reduce the amount of cigarette smoke carcinogens to which the smokers are exposed. Although these methods are, in theory beneficial, it is possible that the perceived availability of "safe" ways to smoke will cause some former smokers to resume smoking and some current smokers to delay quitting. Thus, the extent of exposure reduction and the impact on public health of these methods need to be considered carefully. However, risk reduction and its relation to exposure are not simple to estimate. The way people smoke and the way they respond to carcinogen exposure are both highly variable, as evidenced by the previous history of smokers who switched to light, or low-tar cigarettes. This can actually increase risk in some smokers. The evaluation of exposure reduction will therefore need to be multidisciplinary and include in vitro cell culture studies, animal studies, human clinical studies, and epidemiologic studies. Biomarkers will be critical for rapidly evaluating the effects of new strategies or products to reduce exposure to tobacco smoke carcinogens. No single biomarker will likely satisfy our assessment needs, and so a panel of biomarkers should be used that includes biomarkers of exposure, biologically effective dose, and potential harm. In addition, usefulness of new products will need to be tested in people of different susceptibilities (i.e., who vary in behavior, sex, age, genetics, and prior tobacco use). Even if the new products are shown to be effective at reducing lung carcinogens, they should not be used alone but rather be incorporated into a comprehensive tobacco control program.

Biomarkers↗
PubMed2002

Exposures associated with serum organochlorine levels among postmenopausal women from western New York State.

BACKGROUND: Organochlorines, such as 2,2-bis (4-chlorophenyl)-1,1-dichloroethylene (DDE), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are lipophilic compounds that are ubiquitous in the environment and may cause adverse health effects in humans. METHODS: We examined the correlation between epidemiological exposure variables and serum DDE, PCB, and HCB levels in a sample of 192 healthy, female postmenopausal western New York residents; a subset of the control group from a case-control study on breast cancer risk. Usual diet, reproductive and medical histories, and other lifestyle information were obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, and 69 PCB congeners were determined by gas chromatography with electron capture detection. Statistical analyses included computations of crude and age and lipid adjusted correlation coefficients, as well as multiple linear regression analysis. RESULTS: Results indicated that the strongest predictors for serum DDE levels were age, serum lipids, parity, and fruit and dairy consumption. Statistically significant predictors of PCB levels included age, serum lipids, parity, and fish consumption. Serum HCB levels were related to age, serum lipids, and fruit and red meat consumption. CONCLUSIONS: Our findings are consistent with previous investigations that reported strong associations between organochlorine levels and age and serum lipids. The absence of other data showing an association between fruit intake and organochlorine levels make the importance of this finding unclear.

Age Factors↗
PubMed2002

Dopamine transporter genotype as a risk factor for obesity in African-American smokers.

OBJECTIVE: To assess the association between a polymorphism related to dopamine function, dopamine transport (SLC6A3), and obesity in smokers. RESEARCH METHODS AND PROCEDURES: Logistic regression was used to assess the relationship between this genetic polymorphism and obesity (body mass index > or = 30 kg/m(2)) from a sample of 510 smokers who smoked at least 10 cigarettes per day and who were participating in a study designed to examine genetic and nongenetic predictors of response to a pharmacological treatment. RESULTS: The likelihood of obesity in African Americans (N = 90) with the 10/10 SLC6A3 genotype was 5.16 times that of African Americans with 9/9 or 9/10 SLC6A3 genotypes (odds ratio = 5.16, confidence interval = 1.60 to 16.65). There was no association of the SLC6A3 genotype with obesity for non-Hispanic whites (N = 420). DISCUSSION: These results suggest that variants of the dopamine transporter gene may be related to obesity in African-American smokers. Possible mechanisms responsible for the association between dopamine transport and obesity in African-American smokers are discussed.

Adolescent↗
PubMed2002

Skilled use of DNA polymorphisms as a tool for polygenic cancers.

Association studies are assumed to be an efficient method of deciding whether a gene or its variant is important for cancer. Sequencing data on 30 000 human genes suggest that an average gene contains one to two single nucleotide polymorphisms (SNP), and high through-put technologies have become available for fast genotyping. Because no functional data are available for most SNPs, the result of the large-scale genotyping effort will be a huge amount of data of unknown biological significance. We discuss here the approaches in study design and reporting that will reduce the spread of false positive data and optimize scientific progress in the genotyping field.

False Positive Reactions↗
PubMed2002

The risk of breast cancer associated with dietary lignans differs by CYP17 genotype in women.

Lignans are plant compounds metabolized in the gut to produce the phytoestrogens enterolactone and enterodiol. Reduced breast cancer risks associated with higher urinary lignan excretion may be related to competitive inhibition of endogenous estrogens. Evidence exists that associations with reproductive risk factors for breast cancer differ according to cytochrome P450c17alpha (CYP17) genotype. Genetic variability in estrogen metabolism could affect lignan metabolism thereby modifying risk associations. We examined breast cancer risk, dietary lignans and CYP17 genotype among 207 women with primary, incident, histologically confirmed breast cancer and 188 controls frequency matched to cases by age and county of residence. Self-reported frequency of intake of 170 foods and beverages during the 2 y before the interview and other relevant data were collected by detailed in-person interviews. Dietary lignan intake was expressed as the sum of enterolactone and enterodiol production from foods. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education and other breast cancer risk factors. Women in the highest tertile of dietary lignans tended to have reduced breast cancer risk (OR 0.45, 95% CI 0.20-1.01 and OR 0.59, 95% CI 0.28-1.27, pre- and postmenopausal women, respectively). Substantially reduced risks in the highest tertile of lignans were observed for premenopausal women with at least one A2 allele (OR 0.12, 95% CI 0.03-0.50). Our results suggest that CYP17 genotype may be important in modifying the effect on breast cancer risk of exogenous estrogens, particularly for premenopausal women.

4-Butyrolactone↗
PubMed2002

Pharmacogenetic investigation of smoking cessation treatment.

Despite the efficacy of bupropion for smoking cessation, smokers exhibit variability in treatment outcome. The CYP2B6 gene has been implicated in bupropion kinetics and nicotine metabolism, and is a plausible candidate for pharmacogenetic studies of treatment response. We investigated whether a functional genetic polymorphism in the CYP2B6 gene predicts smoking outcomes in a placebo-controlled randomized trial. Four hundred and twenty-six smokers of European Caucasian ancestry provided blood samples and received bupropion (300 mg/day for 10 weeks) or placebo, plus counseling. Smoking status, abstinence symptoms and side-effects were recorded weekly, and smoking status was verified at the end of treatment and at 6-month follow-up. Smokers with a decreased activity variant of CYP2B6 reported greater increases in cravings for cigarettes following the target quit date and had higher relapse rates. These effects were modified by a significant gender x genotype x treatment interaction, suggesting that bupropion attenuated the effects of genotype among female smokers. We conclude that smokers with the CYP2B6 variant may be more vulnerable to abstinence symptoms and relapse. Bupropion may attenuate these effects, especially among females. Additional trials are warranted to confirm these results, as are studies to explore the neurobiological mechanisms. Such research could ultimately enable practitioners to select the optimal type and dose of medication for individual smokers.

Aryl Hydrocarbon Hydroxylases↗