Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism

Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)-2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX-2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon-type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43-0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51-0.97). We found a significant interaction (p < 0.001) between salmon-type fish intake and a SNP in the COX-2 gene (rs5275: +6365 T/C), but not with the 4 other SNPs examined. We found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01), but no association among carriers of the more common allele. Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX-2 gene.     

SELDI-TOF MS versus prostate specific antigen analysis of prospective plasma samples in a nested case-control study of prostate cancer

There is an urgent need for better biomarkers for detection of clinically significant prostate cancer (PCa). Recent studies suggest that surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) analysis of serum may provide diagnostic information. The aim of this study was to investigate if PCa cases could be identified by applying predefined SELDI-TOF analysis conditions on prospectively, uniformly collected plasma samples from PCa cases and matched controls. Prospective samples from 387 incident PCa cases and an equal number of controls, matched for age and time for recruitment, were analyzed by SELDI-TOF MS (IMAC30/Cu chip) and multivariate classification analysis. Prospective prostate specific antigen levels were subjected to ROC curve analysis giving an AUC of 0.87 for the total cohort with a median lag time between blood sampling and diagnosis of 6.1 years. No markers were found by SELDI-TOF MS that significantly discriminated between cases and controls in the total cohort or in subanalysis of cases with less than 2 years between blood donation and diagnosis (n = 42). Cases with aggressive disease at the time of diagnosis who gave blood less than 4 years prior to diagnosis (n = 23) could however be separated from their controls (sensitivity 70%, specificity 83%) by a model based on SELDI-TOF MS and OPLS-DA data analysis. We were thus not able to confirm previous results with SELDI-TOF MS identifying men with PCa from healthy individuals, but we report an optimal experimental set-up for verification of markers for early detection of cancer in prospectively collected samples.     

A review of the impact of photon and proton external beam radiotherapy treatment modalities on the dose distribution in field and out-of-field; implications for the long-term morbidity of cancer survivors

The use of untraditional treatment modalities for external beam radiotherapy such as intensity modulated radiation therapy (IMRT) and proton beam therapy is increasing. This review focuses on the changes in the dose distribution and the impact on radiation related risks for long-term cancer survivors. We compare conventional radiotherapy, IMRT, and proton beam therapy based on published treatment planning studies as well as published measurements and Monte Carlo simulations of out-of-field dose distributions. Physical dose parameters describing the dose distribution in the target volume, the conformity index, the dose distribution in organs at risk, and the dose distribution in non-target tissue, respectively, are extracted from the treatment planning studies. Measured out-of-field dose distributions are presented as the dose equivalent as a function of distance from the treatment field. Data in the literature clearly shows that, compared with conventional radiotherapy, IMRT improves the dose distribution in the target volume, which may increase the probability of tumor control. IMRT also seems to increase the out-of-field dose distribution, as well as the irradiated non-target volume, although the data is not consistent, leading to a potentially increased risk of radiation induced secondary malignancies, while decreasing the dose to normal tissues close to the target volume, reducing the normal tissue complication probability. Protons show no or only minor advantage on the dose distribution in the target volume and the conformity index compared to IMRT. However, the data consistently shows that proton beam therapy substantially decreases the OAR average dose compared to the other two techniques. It is also clear that protons provide an improved dose distribution in non-target tissues compared to conventional radiotherapy and IMRT. IMRT and proton beam therapy may significantly improve tumor control for cancer patients and quality of life for long-term cancer survivors.     

Relationship between the expression of various markers and prognostic factors in breast cancer

The immunohistochemical detection of six markers of breast cancer has been compared in the present study with known prognostic factors of the disease to establish locally a standard panel of markers for the management of breast cancer. Sections of tissue of 114 consecutive breast cancer cases were studied immunohistochemically, using antibodies against oestrogen receptor (ER), progesterone receptor (PR), androgen receptor, c-erbB2, cathepsin D, and cyclin D. Marker labelling was graded as recommended in the literature. Using the chi(2)-test, relationships were determined between marker labelling and histological type of cancer, tumour grade, tumour size, axillary lymph node status and age of patient. A p value below 0.05 was considered significant. A positive relationship was found between ER and PR and lower grades of cancer, and a negative relationship was found with medullary and atypical medullary carcinoma. The four other markers showed no relationship with grade or type of cancer. All markers showed no significant relationship with size of tumour, presence of axillary node metastasis or age of patient. There was positive correlation between c-erbB2 and cathepsin D. Our study confirms the association between ER and PR and histological type and grade of breast cancer, both known parameters of good prognosis. We found no consistent relationship between the other four markers and prognostic factors studied, other than the suggestion that c-erbB2 and cathepsin D may be useful markers for poor prognosis and can be usefully applied locally, especially in the light of the current availability of trastuzumab (Herceptin) for management of c-erbB2-positive cases. We found no relationship between the markers and tumour size, axillary lymph node status or age.     

In Utero and Childhood Polybrominated Diphenyl Ether Exposures and Body Mass at Age 7 Years: The CHAMACOS Study

Background

Polybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems.

Objective

In this study, we examined whether pre- and postnatal exposure to the components of pentaBDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California.

Methods

We measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index (BMI) at age 7 years.

Results

Maternal PBDE serum levels during pregnancy were associated with higher BMI z-scores in boys (BMI z-score β_adjusted = 0.26; 95% CI: –0.19, 0.72) but lower scores in girls (BMI z-score β_adjusted = –0.41; 95% CI: –0.87, –0.05) at 7 years of age (p_interaction = 0.04). In addition, child’s serum BDE-153 concentration (log₁₀), but not other pentaBDE congeners, demonstrated inverse associations with BMI at age 7 years (BMI z-score β_adjusted = –1.15; 95% CI: –1.53, –0.77), but there was no interaction by sex.

Conclusions

We estimated sex-specific associations with maternal PBDE levels during pregnancy and BMI at 7 years of age, finding positive associations in boys and negative associations in girls. Children’s serum BDE-153 concentrations were inversely associated with BMI at 7 years with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.

Citation

Erkin-Cakmak A, Harley KG, Chevrier J, Bradman A, Kogut K, Huen K, Eskenazi B. 2015. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS Study. Environ Health Perspect 123:636–642; http://dx.doi.org/10.1289/ehp.1408417     

Organophosphate urinary metabolite levels during pregnancy and after delivery in women living in an agricultural community

Little information has been published about pesticide exposures experienced by pregnant women. We measured six dialkyl phosphate (DAP) urinary metabolites of organophosphate (OP) pesticides in 600 pregnant, low-income women living in the Salinas Valley, California, an agricultural area. A total of 28% were employed as farm fieldworkers during pregnancy, and 81% had at least one household member who worked in agriculture. Samples were collected twice during pregnancy (mean = 13 and 26 weeks' gestation, respectively) and just after delivery (mean = 9 days). As in other studies, dimethyldithiophosphate levels were higher than those of other urinary OP metabolites. Total DAP metabolite levels in samples collected after delivery were higher than in samples collected during pregnancy. Median metabolite levels at the first and second prenatal sampling points and at the postpartum collection were 102.8, 106.8, and 227.2 nmol/L, respectively. Both prenatal and postpartum metabolite levels were higher in these Salinas Valley women than in a sample of women of childbearing age in the general U.S. population (National Health and Nutrition Examination Survey), although the deviation from U.S. reference levels was most pronounced after delivery. Higher DAP metabolite levels in the immediate postpartum period may have implications for estimating dose during pregnancy and for exposure during lactation.     

Effects of somatostatin on somatotroph adenomas of the human pituitary: An in vitro functional and morphological study

The effects of somatostatin or the somatostatin analog SMS 201–995 were studied on 4 densely granulated somatotroph adenomas and 4 sparsely granulated somatotroph adenomas in vitro. Release of growth hormone (GH) into culture media during incubation with somatostatin or SMS 201 -995 were measured by radioimmunoassay, and light-microscopical and ultrastructural morphometric parameters were compared with those of cultured control somatotroph adenoma cells of the same tumor. In all tumors except for 1 densely granulated somatotroph adenoma, somatostatin or SMS 201–995 decreased GH release into culture media in 24- and 2-hour incubations. After 48-hour incubation with somatostatin or SMS 201–995, there was no change in cell size or secretory granule diameter. One densely granulated adenoma showed decreased cytoplasmic volume density (CVD) of Golgi apparatus and secretory granules, and a sparsely granulated adenoma had reduced CVD of endoplasmic reticulum. All the tumors that responded with decreased GH release exhibited increased CVD of lysosomes after incubation with somatostatin or SMS 201–995. These results indicate that both densely and sparsely granulated somatotroph adenomas respond to somatostatin inhibition and, furthermore, that inhibition of hormone release is associated with accumulation of lysosomes, suggesting lysosomal degradation of stored hormone. Hospital 20 Nov. (ISSSTE) Coyoacan y Felix Cuevas, Colonia del Valle and (Dept Patologia) y Hospital de Especialidades (C.M.N., IMSS) Cuauhtemoc y Dr. Marquez, Mexico City (IF).