Faculty of Medicine

Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (Mn-SOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the ؊9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk. We also evaluated the effect of the polymorphism on risk among low and high consumers of fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and ␣-tocopherol, with little increased risk for those with diets rich in these foods. Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9 -3.6). No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women. The finding that risk was greatest among women who consumed lower amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer. The abbreviations used are: ROS, reactive oxygen species; SOD, superoxide dismutase; MnSOD, manganese SOD; OR, odds ratio; CI, confidence interval.

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20-0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.

Delineating where human health vulnerability to climate-change is likely to occur is key in formulating effective adaptation strategies. By defining where increased health vulnerability due to a climate-change is likely to occur allows health officials, planners, and decision-makers to develop and focus research adaptation strategies. We take a quantitative approach in determining the health vulnerability due to climate-change, at the national level and level of Skopje as the biggest urban conglomerate in the country. We analyzed heat-related mortality to determine first where climate-sensitive health vulnerabilities occur and secondly to assess the potential effects of climate change. Key areas for the Strategy in adapting to climate change include: adapting the health care infrastructure (hospitals, nursing homes) to be more resilient to the climate change effects. From 2010, a 'Heat-Health Watch' system operates in Macedonia during the summer months, with four levels of r...

Background: The objective of our study was to explore the knowledge, attitudes and practices of Macedonian consumers towards functional foods, to predict future trends and to assess the national public health policies encompassing the functional foods market. Methods: Total of 518 respondents aged 18+, from all regions in the country participated in the study. They were sampled through three-staged national representative sampling procedures. The questionnaire comprised questions regarding the level of information about functional foods, trust in health claims, frequency of consumption and knowledge and attitudes related to those foods. Statistical significance was determined at p<0.05. Results: Respondents aged 18-34 were more informed compared to the total population (22 and 16 % respectively, p<0.05). Most of the consumers consume these products once a day. Employed consumers were willing to increase daily consumption from 3 to 18 % (p<0.05). On average 65.1% of the stat...