Population differences in the testosterone levels of young men are associated with prostate cancer disparities in older men

Although there is evidence that greater exposure to testosterone is associated with an increased risk of prostate cancer, a recent analysis of 18 prospective studies found no relationship between levels of endogenous sex hormones and prostate cancer development. However, the reviewed studies were subject to methodological constraints that would obscure any potential relationship between prostate cancer and androgenic hormones. If prostate cancer risk is mediated by lifetime exposure to testosterone, then case‐control studies that concentrate on endogenous sex hormones near the ages that prostate cancer is diagnosed would provide limited information on cumulative testosterone exposure across the lifespan. Alternately, early adulthood has been suggested as the most salient period to evaluate the influence of steroid physiology on prostate carcinogenesis. As such, an exhaustive literature search was completed to obtain testosterone values reported for study samples of younger men, along with prostate cancer incidences for the larger populations from which the study populations were sampled. A novel analytical method was developed to standardize, organize, and examine 12 studies reporting testosterone levels for 28 population samples. Study populations were generally apportioned according to ethnicity and geographic residence: Americans of African, Asian, Caucasian, and Hispanic ancestry from several different regions within the United States as well as men from China, Germany, Japan, Kuwait, New Zealand, South Korea, and Sweden. Population differences in the testosterone levels of young men were significantly associated with population disparities in the prostate cancer incidence of older men (Spearman's rho = 0.634, p = 0.002). Am. J. Hum. Biol. 2010. © 2010 Wiley‐Liss, Inc.     

Genetic modelling of the estrogen metabolism as a risk factor of hormone-dependent disorders

Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of diseases. Over the last decade individual genetic variability of the estradiol metabolism has been described as a significant contributor to disease susceptibility with variations depending on ethnic background. Among others, genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an important role in this regard. Mutant alleles of the CYP 1A1 gene are major modulators of lung cancer risk among smokers, mediate gender differences in lung cancer susceptibility, and have been associated with an elevated risk for developing breast, prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene modulate the risk for developing prostate, ovarian, lung, and breast cancer. Also, mutations in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma. Mutant CYP 17 alleles are associated with serum and plasma levels of steroid hormones, use of hormone replacement therapy, and the development of endometrial, prostate, and breast cancer. Available data indicate that the protective effect against breast cancer of a later age at menarche is limited to wild-type CYP 17 allele carriers. Among women with the polycystic ovary syndrome, carriage of mutant CYP 17 alleles is sufficient to aggravate the clinical presentation of the disease. Molecular variants of the CYP 19 gene are associated with an increased risk for developing breast cancer, advanced breast cancer stages, and tumor aromatase production. Carriage of a mutant catechol-O-methyltransferase allele is associated with breast cancer, neurologic disorders such as Parkinson's disease, and modulates behavior among patients with schizophrenia, alcoholics and the general population. In summary, the available evidence points to genes that encode estrogen-metabolizing enzymes as strong hereditary determinants of the susceptibility to benign as well as malignant conditions.     

Xenoestrogens may be the cause of high and increasing rates of hormone receptor positive breast cancer in the world

Breast cancer rates are higher in the Western or industrialized world when compared to Africa or Asia. Within the developing world, breast cancer rates are higher in urban areas where people have a more Westernized lifestyle. In addition, there has been a steady increase in the breast cancer incidence across the world. It is already a known fact that the proportion of hormone receptor positive breast cancer cases is higher in the developed world. Evidence from developed countries also shows that most of the increase in breast cancer incidence has been due to an increase in hormone receptor positive breast cancer. Most of the breast cancer incidence can be explained by environmental factors and genetic causes. However, all known risk factors of breast cancer can explain only 30–50% of breast cancer incidence. In the past decade, a number of compounds that affect female hormone homeostasis have been discovered. These xenoestrogens have been shown to cause breast cancer and also induce the expression of hormone receptors in vitro and in vivo. Given the high use of substances containing xenoestrogens in developed regions of the world and their increasing use in urban parts of the developing world, xenoestrogens could be the important cause of high and increasing rates of hormone receptor positive breast cancer across the world. New research in the area of mammary stem cells provides added indication of the probable time period of exposure to xenoestrogens with chronic exposure later in life leading to hormone receptor positive breast cancer and most probable reason behind increasing breast cancer incidence.     

Hormones and breast cancer

The incidence of breast cancer in women varies with age, mammarygland mass and exposure to endogenous and exogenous hormones.Age is the single most important factor and if, as projected,32% of women will be aged >60 years by 2050, world breast cancerincidence will exceed the current 10⁶ per year. Hormonal influencesthat affect growth of the mammary gland increase the risk ofbreast cancer; for example earlier menarche and later menopause.Childbearing protects against later development of breast cancer,and breastfeeding further decreases the risk. The breast cancerrisk declines more with increasing total duration of breastfeeding.Exposure to hormonal contraceptives has been evaluated in acombined reanalysis of data from 51 epidemiological studies.There is a small transient increase in the relative risk ofbreast cancer among users of oral contraceptives but, sinceuse typically occurs at young ages when breast cancer is relativelyrare, such an increase would have little effect on overall incidencerates. In contrast, exposure to menopause hormone treatmentoccurs when the baseline risk of breast cancer is higher, andepidemiological studies and randomized controlled trials consistentlyfind an increase in breast cancer risk with exposure to combinedestrogen and progestogen. Women with a family history of breastcancer in first degree relatives have an increased risk of breastcancer but there is no evidence to suggest that this differsaccording to a woman's use of oral contraceptives or menopausehormone treatment. Selective estrogen receptor modulators areuseful in the treatment and/or prevention of breast cancer dependingon the specific agonist or antagonist effects on estrogen targettissues.     

Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene

OBJECTIVE: The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model. DESIGN: In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks. RESULTS: Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5. CONCLUSIONS: In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.     

Hormone und Mammakarzinom

Hormones and antihormones are important modulators for the development and therapy of breast cancer. Exogenous estrogens moderately increase the risk for breast cancer, whereas antihormones are important tools in reducing the risk for breast cancer as well as its treatment. In this article, we focus on the various effects of hormones (estrogen and progesterone) and antihormones and their clinical application in breast cancer. Various data on different classes of antihormones such as selective estrogen receptor modulators (SERMs), pure antiestrogens, aromatase inhibitors, and gonadotropin-releasing hormone (GnRH) analogues are presented. Breast cancer risk evaluation with regard to the use of hormones and risk reduction through the use of antihormones as preventive agents are discussed. Finally, current recommendations for the therapy of breast cancer using hormones/antihormones in an adjuvant and metastatic setting are depicted.     

Genetic modeling of estrogen metabolism as a risk factor of hormone-dependent disorders

Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of diseases. Over the last decade individual genetic variability of the estradiol metabolism has been described as a significant contributor to disease susceptibility with variations depending on ethnic background. Among others, genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an important role in this regard. Mutant alleles of the CYP 1A1 gene are major modulators of lung cancer risk among smokers, mediate gender differences in lung cancer susceptibility, and have been associated with an elevated risk for breast, prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene modulate the risk for prostate, ovarian, lung, and breast cancer. Also, mutations in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma. Mutant CYP 17 alleles are associated with serum and plasma levels of steroid hormones, use of hormone replacement therapy, and endometrial, prostate, and breast cancer. Available data indicate that the protective effect of a later age at menarche is limited to mutant CYP 17 allele carriers. Among women with the Polycystic Ovary (PCO) syndrome, mutant CYP 17 alleles are sufficient to aggravate the clinical presentation of the disease. Molecular variants of the CYP 19 gene are associated with an increased risk for breast cancer, advanced disease stage, and tumor aromatase production. Carriage of a mutant catechol-O-methyltransferase (COMT) allele is associated with breast cancer, neurologic disorders such as Parkinson's disease, and modulates behavior among patients with schizophrenia, alcoholics and the general population. In summary, the available evidence points to estrogen metabolising genes as strong hereditary determinants of the susceptibility to benign and malignant conditions.     

The role of aromatic hydrocarbons in the genesis of breast cancer.

The incidence of breast cancer in women has increased dramatically over the last decade. Epidemiological markers of this increased incidence include: endocrine related phenomena (early menarche, age of first parity and age of menopause); exposure of the breast to X-radiation; and a group of seemingly disparate factors--urban residence, dietary selection and alcohol consumption. Although experimental breast cancer may be induced by estrogenic hormones, X-radiation and aromatic hydrocarbons, only aromatic hydrocarbons have not been previously implicated in human mammary carcinogenesis. The seemingly unrelated human factors can best be understood by examining the role of breast tissue in aromatic hydrocarbon metabolism. Aromatic hydrocarbons are important environmental chemicals produced by the incomplete combustion of hydrocarbons for use in energy production. Benzene, benz(a)pyrene, dibenz(ah)anthracene and 1-nitropyrene, known experimental breast carcinogens, are produced in this way. Human exposure to aromatic hydrocarbon metabolites induces and promotes altered DNA by mechanisms described as increased intracellular pro-oxidant production as well as direct adduction to DNA. The breast is anatomically embedded in a major fat depot which stores and concentrates aromatic hydrocarbons and can metabolize these hydrocarbons to carcinogenic metabolites. Ductal cells concentrate these metabolites and themselves become target cells for carcinogenesis. Some lifestyle factors increase the amount of carcinogens produced or enhance their activity. A unitary model for mammary carcinogenesis in humans as well as in experimental carcinogenesis is hypothesized. If correct, the hypothesis would account for some of the increase in breast cancer incidence in industrial countries--and would suggest environmental and dietary modifications that would inhibit hydrocarbon induced mammary carcinogenesis.     

Endothelin-secreting tumors and the idea of the pseudoectopic hormone secretion in tumors.

Ectopic hormone secretion in tumor cells is here described as an amplification of hormone production already present in normal, nonendocrine tumor-originated tissue. This idea is tested on the available data regarding endothelin-1 (ET-1) secreting tumors. The endothelins are ubiquitous regulatory peptides produced by various tissues. The precursor cells of many tumor types secrete endothelins. ET-1 protein expression was detected in situ in all tested prostate cancers as well as in normal prostate tissue. The majority of hepatocellular carcinomas produce ET-1, while ET-1 is secreted by the normal hepatic stellate cells. Human breast cancer cells produce immunoreactive ET-1. Similar data exist for pancreatic tissue, the thyroid and large bowel. We can conclude that tumor cells might sustain endothelin secretions already present in the normal tumor-originated tissue. The model that is presented of the pseudoectopic hormone secretion consists of relations between a few parameters. The proportion of hormone-secreting tumors (Th) among all tumors (T) of that organ depends on the amount of the hormone-secreting cells (Ch) among all cells (C) susceptible to malignant transformation. The corrective factor (k) was introduced in the expression Th/T=Ch/C*k, to represent specific conditions altering the malignant transformation probability for a certain normal hormone-secreting cell. In prostate, breast and colon, the kvalue is predicted to be approximately 1, suggesting that ET-1-secreting normal cells are not more prone to the malignant transformation than their neighbours. In liver and pancreas, the incidence of ET-1-secreting tumors outnumbers the proportions of normal ET-1-secreting cells (k values >1). In these organs, normal ET-1-secreting cells seem more likely to turn malignant in comparison to their neighbours, perhaps due to their function, position and exposition to oncogenic factors, or even due to their ET-1 secretion. There are similar data for thyroid and adrenal glands. No ET-1 secretion was reported in kidney neoplasms. Normal renal ET-1 secreting cells might be less prone to turn malignant than other renal cells. Unlse the normal lung tissue, small cell lung cancers often secrete adrenocorticotrophic hormone (ACTH). The pancreatic islet cells do not secrete gastrin, but their tumors often do. Constant k would exceed 1 in both cases. We speculate that these tumors might originate from a small subset of cells with the described feature. Tumor cells sometimes lack features of the normal tissue, as in the cases of the steroid receptor-negative breast cancer. These tumors might originate from the hypothetical subset of receptor-free breast cells. Benign breast epithelial cells lacking oestrogen receptors have been described in cases of megalomastia. These cells might be constituents of normal breasts or, perhaps, present only in cases of increased breast cancer risk.     

A possible link between the pubertal growth of girls and breast cancer in their daughters.

One hypothesis for the origins of breast cancer is that it is initiated by exposure of developing breast tissue in utero to maternal sex hormones. The sex hormone profile is established at puberty, when it regulates growth of the pelvic bones. The pubertal growth of girls is characterized by broadening and rounding of the pelvis. The maximal width between their iliac crests, the intercristal width, increases more rapidly than in boys. We hypothesized that higher sex hormone concentrations at puberty produce larger intercristal widths, and these are markers of increased breast cancer risk in the next generation. We followed up 6,370 women who were born in Helsinki during 1934-1944, and whose mothers' pelvic bones were measured during routine antenatal care. Women whose mothers had large intercristal widths had higher rates of breast cancer. In those born at or after 40 weeks gestation, the hazard ratio for breast cancer was 3.7 (95% CI: 2.1-6.6) if their mother's intercristal width was greater than 30 cm. Among women born to multiparous mothers this hazard ratio rose to 7.2 (3.4-15.4). Hazard ratios for breast cancer were also higher in the daughters of mothers with round iliac crests. Pelvic bone measurements which increase similarly in girls and boys at puberty did not predict breast cancer. We conclude that the intercristal width, and the roundness of the iliac crests, are markers of mothers' sex hormones, and postulate that high concentrations cause genetic instability in differentiating breast cells in their daughters in utero.     

On the possible role of mammary-derived growth hormone in human breast cancer

The incidence of breast cancer has risen worldwide, especially in countries where it used to be low, very probably as a result of economic prosperity and changes in life-style. In women, the available data have resulted in the concept of progression from normal breast development to cancer through precursor lesions sensitive to hormones and growth factors that can be produced locally in the mammary gland, acting as paracrine or autocrine stimulating agents. The local endocrine environment in the breast can be different from the situation in the circulation. In the dog, growth hormone (GH) can be produced locally in the mammary glands and its production can be stimulated by progestins. This GH probably plays a paracrine role in the progesterone-induced proliferation and differentiation of mammary epithelium. There is increasing evidence that the local mammary progestin/GH-axis is operational not only in dogs but also in human breast cancer. No data are yet available on the production of mammary-derived GH in women.     

Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin

OBJECTIVES: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial. METHODS: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up. RESULTS: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors. CONCLUSION: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.     

Smoking (active and passive) and breast cancer: epidemiologic evidence up to June 2001

The first generation of studies evaluating the association between exposure to tobacco smoke and breast cancer merely compared active to nonactive smokers, with varying degrees of detail in the definition of active smoking. With rare exceptions, studies of this kind failed to show an effect of smoking on breast cancer risk. However, such analysis is probably insufficient. The most recent reports on the smoking-breast cancer connection have two characteristics. Some have separated women exposed to passive smoking from those nonexposed to either active or passive smoke. Other reports have focused on factors that modify the effect of smoking on breast cancer incidence, such as genetic markers or hormone receptors. A minority of reports combines these two characteristics. This review addresses the epidemiologic evidence for a link between smoking and breast cancer and discusses the implications of this evidence for future studies.     

The incidence of breast cancer and changes in the use of hormone replacement therapy: A review of the evidence

Even though a link between hormone replacement therapy (HRT) and breast cancer has been well documented in the epidemiological literature since the 1980s, it was not until publication of the results of the Women's Health Initiative (WHI) study in 2002 and the Million Women Study in 2003 that women and doctors started reconsidering the use of HRT and sales of HRT started to drop. This paper evaluates the impact of the publication of these two landmark studies on the expected and observed changes in the incidence of breast cancer.Between 2001–2002 and 2005–2006, sharp and significant reductions in the incidence of breast cancer of up to 22% were reported in many US and European populations, temporally consistent with the drop in usage of HRT. Declines in the rates of breast cancer were strongest for 50–60-year-old women (those most likely to be current users of HRT), affected mainly ER+ and PR+ cancers (those most strongly associated with HRT use), and were largest among women with the highest pre-decline prevalence of HRT use and the sharpest decline in its use.A considerable amount of scientific evidence supports the hypothesis that the decline in the incidence of breast cancer is in large part attributable to the sudden drop in HRT use following publication of the WHI and Million Women studies. Nevertheless, the problem of how to advise women contemplating HRT use today remains. Medical relief will remain necessary for many women with menopausal complaints, and so new therapeutic options need to be explored.     

Breast cancer risk in the WHI study: the problem of obesity

In the climacteric, about 40% of the women have occult breast tumors the growth of which may be stimulated by hormones. Many genetic, reproductive and lifestyle factors may influence the incidence of breast cancer. Epidemiological data suggest that the increase in the relative risk (RR) of breast cancer induced by hormone replacement therapy (HRT) is comparable with that associated with early menarche, late menopause, late first birth, alcohol consumption, etc. One of the most important risk factors is obesity which exceeds the effect of HRT by far, and in overweight postmenopausal women the elevated risk of breast cancer is not further increased by HRT. As in the WHI study the majority of women was overweight or obese, this trial was unsuitable for the investigation of breast cancer risk. In the women treated with an estrogen/progestin combination, the RR of breast cancer rose only in those women who have been treated with hormones prior to the study, suggesting a selection bias. In the women not pretreated with hormones, it was not elevated. In the estrogen-only arm of the WHI study, there was no increase but a steady decrease in the RR of breast cancer during 6.8 years of estrogen therapy. This result was unexpected, as estrogens are known to facilitate the development and growth of breast tumors, and the effect is enhanced by the addition of progestins. Obese women are at high risk to develop a metabolic syndrome including insulin resistance and hyperinsulinemia. In postmenopausal women, elevated insulin levels are not only associated with an increased risk for cardiovascular disease, but also for breast cancer. This might explain the effects observed in both arms of the WHI study: HRT with relative low doses of estrogens may improve insulin resistance and, hence, reduce the elevated breast cancer risk in obese patients, whereas this beneficial estrogen effect may be antagonized by progestins. The principal options for the reduction of breast cancer risk in postmenopausal women are the prevention of overweight and obesity to avoid the development of hyperinsulinemia, the medical treatment of insulin resistance, the use of low doses of estrogens and the reduction of exposure to progestins. The latter might include long-cycles with the sequential use of appropriate progestins every 3 months for 14 days. There are large inter-individual variations in the proliferative response to estrogens of the endometrium. Control by vaginalsonography and progestin challenge tests may help to identify those women who may be candidates for low-dose estrogen-only therapy.     

Denosumab

Denosumab is a fully human monoclonal IgG(2) antibody that binds to receptor activator of nuclear factor-κB ligand (RANKL) and inhibits bone resorption due to RANKL-mediated osteoclastogenesis. In Europe, subcutaneous denosumab is indicated for cancer treatment-induced bone loss in men with prostate cancer and in postmenopausal women with breast cancer. In a large (n= 1468), well designed, multinational, phase III trial in adult patients with prostate cancer who were receiving androgen-deprivation therapy, bone mineral density (BMD) at the lumbar spine was significantly improved from baseline after 24 (primary endpoint) and 36 months of treatment with subcutaneous denosumab (60 mg once every 6 months), relative to that with placebo. Moreover, the risk of new vertebral fracture was significantly reduced by 62% in the denosumab group compared with the placebo group. In breast cancer patients receiving aromatase inhibitor therapy (n =252), subcutaneous denosumab (60 mg once every 6 months) significantly improved BMD at the lumbar spine from baseline after 12 (primary endpoint) and 24 months of treatment relative to placebo in a pivotal phase III trial. There were significant improvements in BMD at all skeletal sites, including the lumbar spine, total hip, and femoral neck, after 24 and 36 months' denosumab treatment in prostate cancer patients and after 12 and 24 months' treatment in breast cancer patients. In general, these improvements occurred irrespective of baseline characteristics, including age, duration of hormone ablation therapy, and baseline BMD. Denosumab treatment was generally well tolerated for up to 24 months in breast cancer patients and for up to 36 months in prostate cancer patients.     

Melatonin in pathogenesis and therapy of cancer

Melatonin is a neuroendocrine hormone secreted by the pineal gland to transduce the body's circadian rhythms. An internal 24 hour time keeping system (biological clock) regulated by melatonin, controls the sleep-wake cycle. Melatonin production is a highly conserved evolutionary phenomenon. The indole hormone is synthesized in the pinealocytes derived from photoreceptors. Altered patterns and/or levels of melatonin secretion have been reported to coincide with sleep disorders, jetlag, depression, stress, reproductive activities, some forms of cancer and immunological disorders. Lately, the physiological and pathological role of melatonin has become a priority area of investigation, particularly in breast cancer, melanoma, colon cancer, lung cancer and leukemia. According to the 'melatonin hypothesis' of cancer, the exposure to light at night (LAN) and anthropogenic electric and magnetic fields (EMFs) is related to the increased incidence of breast cancer and childhood leukaemia via melatonin disruption. Melatonin's hypothermic, antioxidant and free radical scavenging properties, attribute it to an immunomodulator and an oncostatic agent as well. Many clinical studies have envisaged the potential therapeutic role of melatonin in various pathophysiological disorders, particularly cancer. A substantial reduction in risk of death and low adverse effects were reported from various randomized controlled trials of melatonin treatment in cancer patients. This review summarizes the physiological significance of melatonin and its potential role in cancer therapy. Furthermore, the article focuses on melatonin hypothesis to represent the cause-effect relationship of the three aspects: EMF, LAN and cancer.     

Trends in prostate cancer incidence and mortality in Croatia, 1988-2008

Aim

To describe and interpret prostate cancer incidence and mortality trends in Croatia between 1988 and 2008.

Methods

Incidence data for the period 1988-2008 were obtained from the Croatian National Cancer Registry. The number of prostate cancer deaths was obtained from the World Health Organization mortality database. We also used population estimates for Croatia from the Population Division of the Department of Economic and Social Affairs of the United Nations. Age standardized incidence and mortality rates were calculated by the direct standardization method. To describe time trends of incidence and mortality, joinpoint regression analysis was used.

Results

Average age-standardized incidence rate between the first and last five-year period doubled, from 19.0/100 000 in 1988-1992 to 39.1 per 100 000 in 2004-2008. Age-standardized mortality rate increased by 6.9%, from 14.5 to 15.5 per 100 000. Joinpoint analysis of incidence identified two joinpoints. The increasing incidence trend started from 1997, with the estimated annual percent of change (EAPC) of 12.9% from 1997-2002 and of 4.1% from 2002-2008. Joinpoint analyses of mortality identified one joinpoint. Mortality trend first decreased, with EAPC of -3.0% from 1988-1995 to increase later with EAPC of 2.0% from 1995-2008.

Conclusion

The incidence of prostate cancer in Croatia has been on the increase since 1997. Trend in mortality is increasing, contrary to the trends in some higher-income countries. An improvement in the availability of different treatment modalities as well as establishing prostate cancer units could have a positive impact on prostate cancer mortality in Croatia.Prostate cancer has become the most common male cancer in Western populations and the third most common cause of cancer death in Europe (1). In Croatia, it is the third most common male cancer after lung and colorectal cancer. In 2008, 1692 men were diagnosed with prostate cancer and 641 men had prostate cancer certified as cause of death (2,3).There are three well-established risk factors for prostate cancer: increasing age, ethnic origin, and heredity (4). Other factors have also been discussed, such as nutrition, pattern of sexual behavior, alcohol consumption, exposure to UV radiation, and occupational exposure (5).So far, primary prevention of prostate cancer has not been possible, but there are means for secondary prevention. Prostate-specific antigen (PSA) testing was introduced more than 20 years ago (6) and ever since has had a great impact on early prostate cancer detection. However, the existing evidence from meta-analyses of randomized controlled trials does not support the routine use of screening for prostate cancer with PSA (7). In Croatia, PSA testing is applied as a mode of opportunistic screening, defined as individual case findings, which are initiated by the patient and/or his physician.Prostate cancer presents significant burden for society and with the aging of population its incidence is expected to rise further. The aim of this study is to describe and interpret prostate cancer incidence and mortality trends in Croatia between 1988 and 2008 and to compare the current trends to other European countries and propose potential changes in health service to further enhance prostate cancer management.