Mary E. Platek

Mitochondrial copy number and risk of breast cancer: a pilot study.

It has been proposed that the copy number of mitochondria DNA (mtDNA) per cell reflects gene-environment interactions between unknown hereditary factors and exposures affecting levels of oxidative stress. However, whether copy number of mtDNA could be a risk predictor of oxidative stress-related human cancers, such as breast cancer, remains to be determined. To explore the role of mtDNA copy number in breast cancer etiology, we analyzed mtDNA copy number in whole blood from 103 patients with breast cancer and 103 matched control subjects and examined in relation to endogenous antioxidants. Case patients with breast cancer had a statistically significantly higher mtDNA copy number than control subjects (median: 1.29 vs. 0.80, P<0.01). High mtDNA copy number (above the median in controls) was associated with a statistically significantly increased risk of breast cancer, compared with low copy number (Odds ratio (OR)=4.67, 95% CI: 2.45-8.92), with a statistically significant dose-response relationship in trend analysis (P<0.01). Moreover, mtDNA copy number was significantly inversely associated with several important endogenous oxidants and antioxidants in blood in either the cases (total glutathione, CuZn-SOD activity and myeloperoxidase (MPO)) or the controls (catalase (CAT) activity). These results suggest the mtDNA copy number could be associated with risk of breast cancer, perhaps through an oxidative stress mechanism.

Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database.

BackgroundOlfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited.MethodsThe SEER database (1973-2006) was queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry.ResultsA total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery.ConclusionsBest survival results were obtained for surgery with radiotherapy.

Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.

It has been hypothesized that effects of alcohol consumption on one-carbon metabolism may explain, in part, the association of alcohol consumption with breast cancer risk. The methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes express key enzymes in this pathway. We investigated the association of polymorphisms in MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) with breast cancer risk and their interaction with alcohol consumption in a case-control study—the Western New York Exposures and Breast Cancer study. Cases (n = 1,063) were women with primary, incident breast cancer and controls (n = 1,890) were frequency matched to cases on age and race. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. We found no association of MTHFR or MTR genotype with risk of breast cancer. In the original case-control study, there was a nonsignificant increased odds of breast cancer among women with higher lifetime drinking. In the current study, there was no evidence of an interaction of genotype and alcohol in premenopausal women. However, among postmenopausal women, there was an increase in breast cancer risk for women who were homozygote TT for MTHFR C677T and had high lifetime alcohol intake (≥1,161.84 oz; OR, 1.92; 95% CI, 1.13-3.28) and for those who had a high number of drinks per drinking day (>1.91 drinks/day; OR, 1.80; 95% CI, 1.03-3.28) compared with nondrinkers who were homozygote CC. Our findings indicate that among postmenopausal women, increased breast cancer risk with alcohol consumption may be as a result of effects on one-carbon metabolism. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2453–9)

DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR.

Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in the one-carbon metabolism, may alter DNA methylation levels and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata-defined by promoter methylation status for each of three genes, E-cadherin, p16, and RAR-β2 in breast cancer; in addition, we evaluated case-case comparisons of the likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real-time methylation-specific PCRs for 803 paraffin-embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios and 95% confidence intervals. We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, estrogen receptor status, folate intake, and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-β2 genes in breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):998–1002)

Effect Modification by Catalase Genotype Suggests a Role for Oxidative Stress in the Association of Hormone Replacement Therapy with Postmenopausal Breast Cancer Risk

Catalase, a ubiquitous heme enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells from oxidative stress. A C/T polymorphism in the promoter region of the CAT gene (rs1001179) affects transcriptional activity and RBC catalase levels. Oxidative stress may explain the observed increased postmenopausal breast cancer risk associated with hormone replacement therapy (HRT). We examined CAT genotype, HRT, and postmenopausal breast cancer risk in the Western New York Exposures and Breast Cancer case-control study. Cases (n = 616) were women with primary, incident, pathologically confirmed breast cancer. Randomly selected controls (n = 1,082) were frequency matched to cases on age and race. Genotype was assayed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) adjusted for potential confounders. CAT genotype alone was not associated with breast cancer risk. Ever use of HRT was associated with increased risk (OR, 1.39; 95% CI, 1.11-1.75). The increase with ever use was more pronounced among those with variant CT or TT CAT genotype (OR, 1.88; 95% CI, 1.29-2.75) than among those with CC (OR, 1.15; 95% CI, 0.86-1.54). Similarly, risk associated with ≥5 years of HRT use was greater among those with at least one variant T allele (OR, 2.32; 95% CI, 1.50-3.59). Increased risk was limited to estrogen receptor–positive tumors. Our findings suggest that CAT genotype modifies the effect of HRT use on breast cancer risk and that HRT may affect risk by affecting oxidative stress. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1082–7)

Adipokines in Plasma and Breast Tissues: Associations with Breast Cancer Risk Factors

Background: Blood adipokines are associated with breast cancer risk; however, blood–breast adipokine correlations and factors that explain variation in adipokines are unknown. Methods: Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations. Results: Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma–breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma–breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin. Conclusions: Although we report positive plasma–breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis. Impact: A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues. Cancer Epidemiol Biomarkers Prev; 21(10); 1745–55. ©2012 AACR.

Pretreatment nutritional status and locoregional failure of patients with head and neck cancer undergoing definitive concurrent chemoradiation therapy.

This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity‐modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN).

Comparison of the prevalence of malnutrition diagnosis in head and neck, gastrointestinal, and lung cancer patients by 3 classification methods.

Background: Malnutrition is prevalent among patients within certain cancer types. There is lack of universal standard of care for nutrition screening and a lack of agreement on an operational definition and on validity of malnutrition indicators. Objective: In a secondary data analysis, we investigated prevalence of malnutrition diagnosis with 3 classification methods using data from medical records of a National Cancer Institute-designated comprehensive cancer center. Methods: Records of 227 patients hospitalized during 1998 with head and neck, gastrointestinal, or lung cancer were reviewed for malnutrition based on 3 methods: (1) physician-diagnosed malnutrition-related International Classification of Diseases, Ninth Revision codes; (2) in-hospital nutritional assessment summaries conducted by registered dietitians; and (3) body mass indexes (BMIs). For patients with multiple admissions, only data from the first hospitalization were included. Results: Prevalence of malnutrition diagnosis ranged from 8.8% based on BMI to approximately 26% of all cases based on dietitian assessment. &kgr; coefficients between any methods indicated a weak (&kgr; = 0.23, BMI and dietitians; and &kgr; = 0.28, dietitians and physicians)-to-fair strength of agreement (&kgr; = 0.38, BMI and physicians). Conclusions: Available methods to identify patients with malnutrition in a National Cancer Institute-designated comprehensive cancer center resulted in varied prevalence of malnutrition diagnosis. A universal standard of care for nutrition screening that uses validated tools is needed. Implications for Practice: The Joint Commission on the Accreditation of Healthcare Organizations requires nutritional screening of patients within 24 hours of admission. For this purpose, implementation of a validated tool that can be used by various healthcare practitioners, including nurses, needs to be considered.

The Impact of Cancer Treatment on the Diets and Food Preferences of Patients Receiving Outpatient Treatment

Patients undergoing cancer treatment experience a multitude of symptoms that can influence their ability to complete treatment as well as their quality of life during and after treatment. This cross-sectional study sought to describe the dietary changes experienced by cancer patients and to identify associations between these changes and common treatment symptoms. A convenience sample of 1199 cancer patients aged 18 yr and older undergoing active treatment were recruited from 7 cancer centers to complete a self-administered paper-and-pencil survey. Descriptive analyses were conducted to estimate prevalence of dietary changes and chi-squared tests were used to examine associations between dietary changes and health outcomes. Approximately 40% of patients reported a decreased appetite since beginning treatment, and 67.2% of patients reported at least 1 chemosensory alteration. Increased taste sensitivities were more common than decreased taste sensitivities, with increased sensitivity to metallic being the most common taste sensitivity (18.6%). Patients also had increased sensitivities to certain smells including cleaning solutions (23.4%), perfume (22.4%), and food cooking (11.4%). Patients reported a wide range of food preferences and aversions. Patients who had less energy or lost weight since beginning treatment were more likely than others to report treatment-related dietary changes.

Quantification of the effect of treatment duration on local-regional failure after definitive concurrent chemotherapy and intensity-modulated radiation therapy for squamous cell carcinoma of the head and neck

The purpose of this study was to quantify the effect of treatment duration on locoregional progression after definitive concurrent chemoradiation (CCRT) for squamous cell carcinoma of the head and neck (SCCHN).