Nick Dessypris

Leptin and insulin growth factor I in relation to breast cancer (Greece).

AbstractObjectives: Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. Methods: Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. Results: There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. Conclusion: We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.

Low adiponectin levels are associated with renal cell carcinoma: a case-control study.

Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case‐ control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32‐month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR = 0.76, p = 0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra‐abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans.

Leptin and Body Mass Index in Relation to Endometrial Cancer Risk

Background/Aim: Because leptin is a hormone associated with obesity and reproduction, we attempted to examine whether there is a relationship between leptin and endometrial cancer. Methods: Cases were 84 women with histologically confirmed incident endometrial cancer, whereas controls were 84 women admitted to the same hospital for small surgical operations. The serum leptin levels were determined in fasting morning blood samples by using radioimmunoassay. The mean values of leptin levels among cases and controls were compared with simple t test, and the data were further analyzed using multiple logistic regression procedures. Results: The serum leptin levels were 36.7 ± (SD) 25.7 ng/ml among cases and 26.9 ± 19.8 ng/ml among controls (p = 0.006). After adjustment for known risk factors of endometrial cancer, components of the insulin-like growth factor system did not confound the association of leptin with endometrial cancer, but this association was eliminated, when the body mass index was adjusted for. Thus, the odds ratio for an increment of 1 SD of blood leptin was 1.52 (p = 0.03) before adjustment for body mass index, but only 1.13 (p = 0.62) after adjustment for it. Conclusions: In a case-control study of incident endometrial cancer in Greece, we found evidence that leptin is strongly positively associated with endometrial cancer. It cannot be conclusively inferred, however, whether leptin elevation, as a consequence of obesity, plays a role in endometrial carcinogenesis or whether it is a simple correlate of obesity.

Diet in relation to endometrial cancer risk: a case-control study in Greece.

The risk of endometrial cancer is positively associated with obesity, but the role of specific nutrients remains unclear. Given the distinct characteristics of the Greek diet and the low incidence of this form of cancer among Greek women, we undertook a case-control study to investigate the association of endometrial cancer with food groups and micronutrients. Cases were 84 women with histologically confirmed endometrial cancer and controls were 84 women with intact uterus admitted to the same teaching hospital in Athens, Greece. Consumption of pulses, nuts, and seeds was significantly inversely related to the risk for endometrial cancer. No other significant association with food groups was detected, although a protective effect of added lipids, which in the Greek diet are primarily represented by olive oil, was highly suggestive. Retinol, nicotinic acid, vitamin B-6, and riboflavin were inversely associated with the disease. These findings need to be replicated, because this was a relatively small study with the statistical power to detect only strong associations between cases and controls; they appear, however, to support a role of diet in the etiology of endometrial cancer.

Adiponectin in relation to childhood myeloblastic leukaemia

Adiponectin, an adipocyte-specific secretory protein known to induce apoptosis, has been reported to be inversely related to breast and endometrial cancers and recently found to inhibit proliferation of myeloid but not lymphoid cell lines. We hypothesised that adiponectin may be inversely associated with acute myeloblastic leukaemia (AML), but not with acute lymphoblastic leukaemia of B (ALL-B) or T (ALL-T) cell origin in children. Blood samples and clinical information were collected over the period 1996–2000 from 201 children (0–14 years old) with leukaemia (22 AML, 161 ALL-B and 18 ALL-T cases) through a national network of childhood Hematology-Oncology units in Greece and from 201 controls hospitalised for minor pediatric ailments. Serum adiponectin levels were measured under code, at the Beth Israel Deaconess Medical Center, Boston, MA, USA using a radioimmunoassay procedure. Each of the three leukaemia groups was compared with the control group through multiple logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) for an increase of adiponectin equal to 1 s.d. among controls were estimated controlling for gender, age, as well as for height and weight, expressed in age–gender-specific centiles of Greek growth curves. Adiponectin was inversely associated with AML (OR=0.56; 95% CI, 0.34–0.94), whereas it was not significantly associated with either ALL-B (OR=0.88; 95% CI, 0.71–1.10) or ALL-T (OR=1.08; 95% CI, 0.67–1.72). Biological plausibility and empirical evidence point to the importance of this hormone in the pathogenesis of childhood AML.

Factors affecting motorcycle helmet use in the population of Greater Athens, Greece

Objectives—Helmet use is the best preventive measure available against two wheel motorized vehicle (TWMV) related head injuries. In some countries, however, helmets are used only by a minority of TWMV riders. In collaboration with the Road Traffic Police Department, an inspection survey was undertaken to assess the prevalence and to determine predictors of helmet use. Setting—The Greater Athens area, Greece, during July and August 1998. Methods—A total of 982 TWMVs were stopped, 349 of which had two riders (36%). All riders were interviewed by staff members of the Centre for Research and Prevention of Injuries among the Young. Results—The average prevalence of helmet use was 20.2%. It ranged from 9.7% on small suburban roads to 50.8% on highways. Prevalence of use was significantly lower during the weekend days and at night. Women were significantly more likely to wear a helmet and, controlling for gender, drivers were significantly more likely to be helmet users. Riders of more powerful TWMVs and passengers, who themselves had a TWMV driving license, were helmet users more frequently. Among non-users, the majority (46%) indicated that “the helmet made them feel uncomfortable”, particularly in warm weather, whereas 18% claimed that there was little need for a helmet in low speed riding. Conclusions—A multipronged campaign is urgently needed in Greece to increase the prevalence of helmet use by TWMV riders. The campaign should include not only police enforcement but also initiatives to make helmets more convenient to wear and less expensive.

A quantification of preventable unintentional childhood injury mortality in the United States

Objective: To calculate the preventable fraction of unintentional childhood injury deaths in the United States. Design: Ecological study of cause specific unintentional childhood injury mortality rates across the 50 states (and the District of Columbia) of the United States (US) over the 10 year period 1989–98. Methods: The internet accessible database from the National Center for Injury Prevention and Control was used in order to estimate unintentional childhood (0–14 years) injury mortality rates by external cause and time trends over the study period for each of the US states and for the four major geographical regions of the country. In the principal analysis, a calculation was made of the fraction and absolute number of unintentional childhood injury deaths that could have been prevented annually if the mortality rate in the region with the lowest rate also existed in the remaining three. In another scenario, the lowest external cause specific unintentional childhood injury mortality rates from the 50 US states and the District of Columbia were summed to provide the “ideal” lowest conceivable unintentional childhood injury mortality rate from all causes. Ecological correlations between unintentional childhood injury mortality rates from specified external causes, median income, and percent of the population with a college degree were made. Main outcome measures: Unintentional childhood injury mortality rates by cause. Results: Unintentional childhood injury mortality rate declined by 3.5% per year in the country as a whole. If every region of the US had experienced the same injury rate as the Northeast, then one third of all unintentional childhood injuries would not have occurred. More optimistic scenarios indicate that up to two thirds of all unintentional childhood injury deaths could be prevented. Across states, unintentional childhood injury mortality is strongly inversely related to median income. Conclusions: About one third of all unintentional childhood injury deaths in the US are preventable with the means and resources available in the Northeastern states. Among the relevant characteristics in the Northeast region, in comparison with other US regions, are the higher education level of parents, the lower gun ownership, the higher population density that implies shorter distances traveled by cars, a better developed emergency medical system, and the existence of several injury prevention programs.

Baldness and other correlates of sex hormones in relation to testicular cancer.

There is evidence that sex hormones and intrauterine factors are involved in the etiology of testicular cancer. We evaluated the importance of perinatal and adult life correlates of sex hormones as risk factors for testicular cancer in a case control study of 97 incident, histologically confirmed cases, residents of the Greater Athens area and environs, who were diagnosed in the 3 specialized cancer hospitals and the major General Hospital in Athens during the 2 year period 1993‐94. Cases were age‐matched to 2 healthy controls from the same study base. Both cases and controls as well as their mothers were interviewed by the same investigator and the data were analyzed through conditional logistic regression. The odds ratio for testicular cancer was elevated among persons born after a pregnancy characterized by severe nausea. Among the adult life factors, higher body mass was associated with reduced risk, as was evidence of baldness. To the extent that nausea during pregnancy reflects higher levels of pregnancy estrogens on the one hand, and baldness is linked to androgens on the other, our data suggest that estrogens in the intrauterine life and androgens at later stages may have sequential opposing effects for the development of testicular cancer. I J. Cancer 71: 982‐985, 1997.

Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer : two case-control studies

Background: Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and/or whether adiponectin receptors are expressed in lung cancer remains unknown. Methods: We conducted a case-control study of 85 patients with incidental, histologically confirmed lung cancer and 170 healthy controls matched by gender and age. In a separate study, archival lung specimens from 134 cancerous and 8 noncancerous tissues were examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. Results: Tobacco smoking, heavy alcohol intake and education were all associated with lung cancer risk, whereas serum adiponectin levels were not significantly different between cases and controls (multiple logistic regression, odds ratio per SD of adiponectin among controls: 1.13, 95% confidence interval: 0.64–2.02). Adiponectin levels were significantly lower (odds ratio: 0.25, 95% confidence interval: 0.10–0.78) among patients with advanced compared to those with limited disease stage. Expression of adiponectin receptors was apparent only in the cancerous lung tissue (64.2% AdipoR1 and 61.9% AdipoR2 in cancerous vs. 0% among noncancerous tissue). Specifically, AdipoR1 was expressed in all disease types, but no difference was noted with disease stage, whereas AdipoR2 was mainly expressed in the non-small cell carcinomas and more prominently in the advanced disease stage (80%). Conclusions: Circulating adiponectin levels are not different in cases of this malignancy – which seems to be unrelated to obesity and insulin resistance – compared to their healthy controls, though hormonal levels were significantly lower in advanced versus limited lung cancer. Both adiponectin receptors were expressed in cancerous lung tissue, but not in normal control tissue and there was a differential expression by disease stage. These findings should be further explored, especially in the context of the recently reported protective effect of thiazolidinediones in diabetic patients with lung cancer.

Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin‐like growth factor‐I (IGF‐I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP‐3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF‐I and IGFBP‐3 were undertaken using commercially available radioimmunoassays. Serum IGF‐I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF‐I and the likelihood of childhood leukaemia, but an increment of 1 μg/ml of IGFBP‐3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP‐3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF‐I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF‐I in the blood in comparison to those of IGFBP‐3 are likely to hinder documentation of an underlying positive association of IGF‐I with the disease. Int. J. Cancer80:494–496, 1999.