Breast cancer risk assessment in the Czech female population – an adjustment of the original Gail model

Summary Background. Several mathematical models have been developed for predicting individual breast cancer risk. Such models can help clinicians to choose appropriate preventive and therapeutic interventions for each patient. Unfortunately, the validity of these models has not been tested outside the USA.   Methods. The authors describe a case–control study in the Czech Republic with a similar design to that of the US Breast Cancer Detection and Demonstration Project (BCDDP). The main objective of the study was to evaluate the validity of the Gail model in the Czech female population, and to develop a local model using the same statistical approach as the Gail model. Between November 2000 and May 2004, 14,566 questionnaires containing case history data from both healthy women (control group) and women with breast cancer were collected. Case–control age-matched pairs (n = 4598) have subsequently been matched and analyzed.   Results. Our results show that the original Gail model was not able to properly distinguish between controls and breast cancer cases in the Czech female population. Based on paired data, the mean 5-year and life-time breast cancer risk was 1.379 ± 0.668 and 7.990 ± 3.184 in the control group and 1.375 ± 0.692 and 8.028 ± 3.506 in the patients with breast cancer group. The original Gail model was also not able to properly describe age-specific baseline risk of breast cancer development in the Czech population. In response the authors developed two variants of modified/locally adjusted models.   Conclusion. The original Gail model is not an accurate breast cancer risk assessment tool for the Czech female population.     

Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case�Ccontrol study

Objective

Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown.

Methods

These questions were investigated in a case?Ccontrol study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls.

Results

Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06?C2.15; for estradiol, OR = 1.50, 95% CI = 1.03?C2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk.

Conclusion

Our findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation.     

Demographic transition – Cancer trends in geriatric population of North India

Developing countries like India are witnessing a demographic transition resulting in population ageing. This population expansion will in future increase the burden of diseases more prevalent in older patients. Since cancer incidence increases with age, a surge in geriatric patients with cancer will soon overburden the health care system of our country. In anticipation of this change, present retrospective study done at a tertiary care centre highlights the cancer spectrum in all age groups with emphasis on geriatric patients. We stress upon the need for specialised care of these patients in India.     

A genetic variant in microRNA target site of TGF-β signaling pathway increases the risk of colorectal cancer in a Chinese population

Evidence shows that single-nucleotide polymorphisms in microRNA (miRNA) target sites can create, destroy, or modify the miRNA/mRNA binding, therefore modulating gene expression and affecting cancer susceptibility. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in tumor initiation and progression. Intriguingly, recent advances of genome-wide association studies have identified multiple risk loci in this pathway to be associated with risk of colorectal cancer (CRC). To test the hypothesis that genetic variants in miRNA target sites in genes of the TGF-β signaling pathway may also be associated with CRC risk, we first systematically scanned the single-nucleotide polymorphisms (SNPs) in genes of TGF-β signaling pathway which potentially affect the miRNA/mRNA bindings. Through a series of filters, we narrowed down these candidates to four SNPs. Then, we conducted a case–control study with 600 CRC patients and 638 controls in Han Chinese population. We observed that compared with A carriers (AA?+?AG), the GG genotype of rs12997:ACVR1 is associated with a significantly higher risk of CRC (OR?=?1.52, 95 % confidence interval (95 % CI)?=?1.04–2.21, P?=?0.031), particularly in nonsmokers with a higher OR of 1.63 (95 % CI?=?1.04–2.55, P?=?0.032). Our study suggested that SNPs in miRNA target sites could contribute to the likelihood of CRC susceptibility and emphasized the important role of polymorphisms at miRNA-regulatory elements in carcinogenesis.     

Do the risk factors of age,family history of prostate cancer or a higher prostate specific antigen level raise anxiety at prostate biopsy?

To date, little is known of the impact knowledge of personal risk factors has on anxiety in men undergoing biopsy tests for prostate cancer. This analysis explores anxiety scores of men at higher risk due to age, family history of prostate cancer and a higher prostate specific antigen (PSA) level when proceeding from PSA test to prostate biopsy. A prospective cohort of 4198 men aged 50–69 years with a PSA result of >3 ng/ml was studied, recruited for the Prostate testing for cancer and Treatment study (ProtecT). Anxiety scores at the time of biopsy were lower in older men (p < 0.001). No age group showed an increase in anxiety as the men proceeded from PSA testing to biopsy, although older men did not show the same level of decrease in anxiety as younger men (p = 0.035). There was no difference in anxiety scores at biopsy between men with or without a family history of prostate cancer (p = 0.68), or between those with a raised PSA of 10–<20 ng/ml compared to a PSA result of 3–<10 ng/ml (p = 0.46). Change in scores since the initial PSA test appeared unaffected by family history (p = 0.995) or by PSA result (p = 0.76). Within the context of a research study, the increased risk of prostate cancer through older age, having a family history of prostate cancer, or having a significantly elevated PSA level appears to have no detrimental effect on men’s anxiety level when proceeding to biopsy.     

‘Charting a new course for prostate cancer’ – currying favor for docetaxel in hormone-sensitive metastatic prostate cancer

Docetaxel has an established role in the treatment of metastatic castrate-resistant prostate cancer. A number of recent treatments have been shown to improve the survival outcomes for this group of patients and many with improved toxicity profiles, bringing the role of docetaxel into question. We discuss the results and implications of the CHAARTED study that demonstrated a significant improvement in overall survival with docetaxel in metastatic hormone-sensitive prostate cancer.     

Trends in non-metastatic prostate cancer management in the Northern and Yorkshire region of England, 2000�C2006

Background:

Our objective was to analyse variation in non-metastatic prostate cancer management in the Northern and Yorkshire region of England.

Methods:

We included 21 334 men aged ⩾55, diagnosed between 2000 and 2006. Principal treatment received was categorised into radical prostatectomy (11%), brachytherapy (2%), external beam radiotherapy (16%), hormone therapy (42%) and no treatment (29%).

Results:

The odds ratio (OR) for receiving a radical prostatectomy was 1.53 in 2006 compared with 2000 (95% CI 1.26–1.86), whereas the OR for receiving hormone therapy was 0.57 (0.51–0.64). Age was strongly associated with treatment received; radical treatments were significantly less likely in men aged ⩾75 compared with men aged 55–64 years, whereas the odds of receiving hormone therapy or no treatment were significantly higher in the older age group. The OR for receiving radical prostatectomy, brachytherapy or external beam radiotherapy were all significantly lower in the most deprived areas when compared with the most affluent (0.64 (0.55–0.75), 0.32 (0.22–0.47) and 0.83 (0.74–0.94), respectively) whereas the OR for receiving hormone therapy was 1.56 (1.42–1.71).

Conclusions:

This study highlights the variation and inequalities that exist in the management of non-metastatic prostate cancer in the Northern and Yorkshire region of England.     

Obesity in breast cancer – What is the risk factor?

Environmental factors influence breast cancer incidence and progression. High body mass index (BMI) is associated with increased risk of post-menopausal breast cancer and with poorer outcome in those with a history of breast cancer. High BMI is generally interpreted as excess adiposity (overweight or obesity) and the World Cancer Research Fund judged that the associations between BMI and incidence of breast cancer were due to body fatness. Although BMI is the most common measure used to characterise body composition, it cannot distinguish lean mass from fat mass, or characterise body fat distribution, and so individuals with the same BMI can have different body composition. In particular, the relation between BMI and lean or fat mass may differ between people with or without disease. The question therefore arises as to what aspect or aspects of body composition are causally linked to the poorer outcome of breast cancer patients with high BMI. This question is not addressed in the literature. Most studies have used BMI, without discussion of its shortcomings as a marker of body composition, leading to potentially important misinterpretation. In this article we review the different measurements used to characterise body composition in the literature, and how they relate to breast cancer risk and prognosis. Further research is required to better characterise the relation of body composition to breast cancer.     

COX-2 inhibition: a possible role in the management of prostate cancer?

There is mounting evidence to support a role for cyclooxygenase-2 (COX-2) inhibitors (coxibs) in the management of prostate cancer. This review considers the current evidence base for the use of coxibs in prostate cancer as well as their adverse event profile. A systematic literature review using the search terms 'cyclooxygenase', 'COX-2', 'coxibs', 'cardiovascular risk', and 'prostate cancer' was performed using Medline. Celecoxib appears safer in terms of cardiovascular toxicity than other coxibs, and this may relate to its lower selectivity for the COX-2 enzyme. This lower selectivity also provides rationale for its putative broader anti-cancer effects, via non-COX-2-dependent pathways that affect cell cycle regulation, angiogenesis, and hypoxic modulation. There are also interacting relationships between COX-2, chronic inflammation, and prostate cancer. There is much promise for the coxibs as anti-cancer agents. The future might be to pharmacologically adapt these agents to exert their COX-2 independent mechanisms of action while minimizing their COX-2-dependent adverse cardiovascular effects.     

What's new in the treatment of advanced prostate cancer?

Increased insight into the biology of prostate cancer and the emergence of new therapeutic strategies and chemotherapeutic agents has changed approaches in treating patients with advanced prostate cancer. After secondary hormonal manipulations, new approaches include: second-line hormonal therapy, chemotherapy, immunotherapy with granulocyte macrophage-colony stimulating factor (GM-CSF) therapy, dendritic cell therapy, gene vaccination therapy, inhibition and/or blockade of growth factor receptors or growth factor receptor pathways, inhibition of neo-angiogenesis and inhibition of invasion and metastases.     

Colorectal cancer as a complex disease: defining at-risk subjects in the general population – a preventive strategy

Over the last few decades it has become clear that highly penetrant disease genes are responsible for a minor proportion of colorectal cancer cases. Families with hereditary syndromes are today recognized and included in surveillance programs known to reduce morbidity and mortality in colorectal cancer. Colorectal cancer is preventable and screening strategies in whole populations are currently under debate. Colorectal cancer can be considered a complex disease, with a combination of predisposing genetic variants and environmental factors that contribute to the illness as a whole. The progress made in the genome project provides an opportunity to determine such genetic variants and environmental factors. This knowledge can be used to define a subpopulation at increased risk for colorectal cancer. It will be more feasible to design preventive strategies for this subgroup than for a whole population.     

Early-onset baldness and the risk of aggressive prostate cancer: findings from a case–control study

Purpose

We aimed to evaluate the associations between androgenetic alopecia at a young age and subsequent development of aggressive prostate cancer (PC).

Methods

Using a case–control design with self-administered questionnaire, we evaluated the association between aggressive PC and very early-onset balding at age 20, and early-onset balding at age 40 years in 1,941 men. Cases were men with high-grade and/or advanced stage cancer and controls were clinic based men who had undergone biopsy and were found to be histologically cancer negative. Additionally, for cases we assessed whether early-onset balding was associated with earlier onset of disease.

Results

Men with very early-onset balding at age 20 years were at increased risk for subsequent aggressive PC [odds ratio (OR) 1.51, 95% confidence interval (CI) 1.07–2.12] after adjustment for age at baseline, family history of PC, smoking status, alcohol intake, body shape, timing of growth spurt and ejaculatory frequency. Additionally, these men were diagnosed with PC approximately 16 months earlier than cases without the exposure. The effect was present particularly for men with advanced stage pT3+ disease (OR 1.68, 95% CI 1.14–2.47) while men with organ-confined high-grade (8–10) PC did not exhibit the same relationship. No significant associations were observed for men who were balding at age 40 years, given no balding at age 20.

Conclusion

Men with androgenetic alopecia at age 20 years are at increased risk of advanced stage PC. This small subset of men are potentially candidates for earlier screening and urological follow-up.

     

The effects of CYPIA1 gene polymorphism and p16 gene methylation on the risk of lung cancer in a Chinese population

Objective： To investigate the relationship between the genetic polymorphism of CYP1A1 and the genetic susceptibility to lung cancer as well as to study the effects of the methyiation in p16 gene on the risk of lung cancer in a Chinese population. Methods： A case control study was conducted among 47 cases of lung cancer and 94 controls. The genetic polymorphism of CYP1A1 was tested with method of PCR-RFLP, and a methylation-specific PCR （MSP） was performed to detect p16 methylation. Results： It showed that there was no significant difference in frequencies of the genotypes of CYP1A1 between the two groups （P 〉 0.05）. Synergistic effects were not found between smoking and CYP1AI. Methylated p16 gene was found in 44.7% （21/47） of lung cancer tissues and in 17.0% （8/47） of normal lung tissues with significant difference （P 〈 0.05）. Conclusion： The genetic polymorphism of CYP1A1 does not increase the risk of lung cancer in a Chinese population. The methylation in p16 gene may be the most common mechanism to inactivate p16 gene in lung cancer, and is not significantly associated with genotype of CYP1A1,     

Evaluation of the legal risk of a ‘missed’ cancer in two breastscreen services

Variation in opinions of medical experts is a problem for both the legal and medical profession. This is particularly relevant in breast imaging. BreastScreen Queensland and New South Wales have developed a review protocol to assess ‘reasonableness’ of radiological opinions. It is hoped that the protocol will be acceptable to the courts and will result in a fair outcome for all parties involved in a medico-legal dispute.