A common biological basis of obesity and nicotine addiction.

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 × 10(-5)) and CPD (P=9.3 × 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Snus use and other correlates of smoking cessation in the Swedish Twin Registry.

BACKGROUND: We investigated 12 variables and their interactions as correlates of smoking cessation among regular smokers in the population-based Swedish Twin Registry (STR). METHOD: Detailed information on tobacco use and personal characteristics were available from 14 715 male and female twins aged 42-64 years who participated in a screening of the population-based STR and reported being regular smokers in their lifetime. A two-stage analytic design was used to examine correlates of smoking cessation. The sample was split at random and significant main effects and interactions identified in the testing set were examined in the validation set. Hazard ratios (HRs) and 95% confidence intervals (CIs) describe the association between correlates and smoking cessation. RESULTS: Twelve main effects were significantly associated with smoking cessation in the testing set; eight were confirmed in the validation set. Of the nine interactions identified in the testing set, none remained significant when evaluated in the validation set after Bonferroni correction. HRs were highest for Swedish oral smokeless tobacco (snus) use (HR 2.70, 95% CI 2.30-3.20), >11 years of education (HR 1.57, 95% CI 1.43-1.73) and being married or cohabitating (HR 1.51, 95% CI 1.39-1.63). Although not statistically significant after Bonferroni correction, snus use also appeared important in the context of interactions, where lower nicotine dependence score, higher socio-economic status (SES) and greater body size were associated with smoking cessation only among participants who never used snus. CONCLUSIONS: Snus use was the strongest independent correlate of smoking cessation. Further studies should investigate the mechanism of this association.

Is Swedish snus associated with smoking initiation or smoking cessation?

Nicotine replacement therapies (NRT) are an effective treatment for tobacco dependence, yet most smokers do not quit or remain abstinent. We investigated whether Swedish snus (snuff) use was associated with smoking cessation among males participating in a large population based twin study in Sweden. Snus use was associated with smoking cessation but not initiation. Given that snus delivers comparable nicotine concentrations but carries lesser cancer risk than cigarettes, snus may be a widely used, non-medical form of NRT. Evaluation of the efficacy of snus for smoking cessation should be evaluated in randomised clinical trials.

Reproductive factors in relation to breast cancer characterized by p53 protein expression (United States).

OBJECTIVE: To evaluate the potential etiologic heterogeneity of breast cancer by examining whether associations with reproductive and other personal characteristics differed by p53 protein expression status. METHODS: Data from the Carolina Breast Cancer Study, a population-based, case-control study of 861 cases and 790 controls, were utilized. Immunohistochemical staining for the p53 protein was performed on 638 archived tumor specimens; 46% of cases were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for p53+ and p53- breast cancer relative to controls for reproductive and other personal characteristics. Analyses were performed separately for younger (< or = 45 years) and older (>45 years) women. RESULTS: Risk factor profiles largely overlapped for p53+ and p53- breast cancer, with the exception of oral contraceptive (OC) use among younger women and a family history of breast cancer. Prolonged OC use was more strongly associated with p53+ breast cancer [OR 3.1 (95% CI: 1.2-8.1) than p53- breast cancer (OR 1.3 (95% CI: 0.6-3.2)] among younger women only. A first-degree family history of breast cancer was associated with p53+ breast cancer among younger women [OR 1.5 (95% CI: 1.0-2.2)] and older women [OR 1.4 (95% CI: 0.9-2.3)], but not p53- breast cancer in either age-group. CONCLUSIONS: These results provide little evidence of breast cancer heterogeneity as classified by p53 expression status. However, although not statistically significant, OC use among younger women and family history of breast cancer may operate through a pathway involving p53 alterations to increase risk of breast cancer.

Tumor characteristics in African American and white women.

BACKGROUND: Previous studies provide evidence that breast cancers occurring in different age and ethnic groups are not evenly distributed with regard to their biologic, pathologic and clinical characteristics. We evaluated the distributions of 11 pathological and biological variables between African-American (AA) and white patients and between three different age groups (20-39, 40-59 and 60-74 years). We examined whether racial differences existed across levels of age. METHODS: Data were obtained from the Carolina Breast Cancer Study (CBCS), a population-based, case-control study of breast cancer in North Carolina. Eighty hundred and sixty one women with a first diagnosis of invasive breast cancer participated in Phase I of the CBCS. Diagnostic paraffin blocks were obtained from 807 cases. One representative block was scored for histologic type and grade (architectural, nuclear, mitotic and overall). Medical chart review yielded tumor size, lymph node status, distant metastases, stage, hormone receptor status (ER/PR) and DNA ploidy. RESULTS: Pathologically advanced tumors (large size, high grade, high stage, ER/PR negative) were significantly more common in young and AA women. Racial differences varied by age. Among younger, AAs and whites differed only with respect to ER/PR status, while among older women AAs and whites differed only with respect to stage at diagnosis. CONCLUSIONS: The results of this study confirm the presence of poorer prognosis breast cancer among AA and younger women. They also highlight the need for age and race to be considered together when evaluating pathologic and biologic characteristics of disease and when making inferences regarding tumor aggressiveness.

Lactation and breast cancer risk.

BACKGROUND: Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in African-American and white women residents of North Carolina, were evaluated to determine whether specific aspects of lactation are associated with a reduction in the risk of breast cancer. METHODS: Analyses included 751 parous cases and 742 parous controls frequency-matched on age and race. Information on lactation, reproductive history, lifestyle characteristics and family history were obtained through a personal interview. RESULTS: When women who breastfed were compared to those who never breastfed, odds ratios and 95% confidence intervals of 0.8 (0.5-1.1) and 0.7 (0.5-0.9) were found for women 20-49 years and 50-74 years, respectively. Similar inverse associations were observed for each of three categories of lifetime duration (1-3, 4-12, 13+ months). The inverse associations persisted and did not vary when number of children breastfed, ages at first and last lactation and lactational amenorrhoea were examined. CONCLUSIONS: Our findings suggest that any lactation, regardless of duration or timing, is associated with a slight reduction in the risk of breast cancer among younger and older parous women.

Effect of pretreatment with 0.9% sodium chloride or insulin solutions on the delivery of insulin from an infusion system.

The effect of pretreating a polyvinyl chloride i.v. administration system with sodium chloride or insulin solution on the delivery of insulin was studied. Insulin labeled with iodine 125 was added to human insulin, which was added to 0.9% sodium chloride injection packaged in flexible polyvinyl chloride containers and to 0.9% sodium chloride injection placed in empty ethylene vinyl acetate containers. Samples were tested for insulin content by gamma spectrometry after storage in the bags and after infusion through four different polyvinyl chloride administration sets at different flow rates. Effluent samples were collected at 10 times (6-50 minutes) after the start of the infusion. The 0.9% sodium chloride injection had a conditioning effect on the polyvinyl chloride administration sets, indicating an electrostatic sorption mechanism for insulin. Sorption to the untreated polyvinyl chloride sets and the ethylene vinyl acetate bags was substantial and followed a Langmuir adsorption isotherm. Insulin sorption to the untreated administration sets was greatest from the first 100 mL of effluent and did not differ by flow rate or type of set investigated. Storing the sodium chloride injection in the tubing for one hour or flushing the tubing with 100 mL of sodium chloride injection or 100 mL of the insulin admixture decreased sorption by half. Storing the insulin admixture in the tubing for 30 minutes caused sorption to be reduced by a factor of three. When either of the solutions was stored in the set and then the set was flushed with the solution, sorption was even further suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)