Gene polymorphisms in bladder cancer

In Europe, cancer of the bladder is the fourth most common cancer among men, accounting for 7% of total cancers. In the USA, bladder cancer is the fifth most common cancer in men and seventh in women. This disease is three times more common in men than in women. Several risk factors, such as cigarette smoking and occupational chemical exposure, contribute to bladder cancer development. The balance between activation and detoxification of carcinogens affects the amount of DNA damage that accumulates in cells. The entire process leading to DNA damage and subsequent repair of the damage involves a host of enzymes, many of which are polymorphic. Polymorphisms in metabolic enzyme genes and repair genes may cause alterations in protein product functions that can finally lead to genomic instability and carcinogenesis. In this article, we review the polymorphisms in a number of genes that have been found to be the modulators of bladder cancer risk. Improved understanding of the molecular biology of urothelial malignancies is helping to more clearly define the role of new prognostic indices and multidisciplinary treatment for this disease.     

Men's Health and the Excess Burden of Cancer in Men

ContextMen seem to be at greater risk of both developing and dying from those cancers that should affect men and women equally.ObjectiveIn this review, we argue for a more proactive approach to be adopted in relation to men's increased susceptibility to cancer.Evidence acquisitionCancer data from Cancer Research UK and the UK National Cancer Intelligence Network were reviewed.Evidence synthesisIn the United Kingdom, men have a 69% higher mortality rate and a 62% higher incidence rate for the major cancers, which should affect men and women equally. The rate of premature death is correspondingly high, with more than 37 000 additional years of life presumably lost for working-age men (15–64 yr) as a result of death from cancer. This pattern is repeated elsewhere but has received little attention.ConclusionsIt is unclear why men are at greater risk, but a more proactive approach should be taken to identify this issue as worthy of exploration and to reach out to men at risk.     

Effective follow-up for recurrence or a second primary cancer in patients with early gastric cancer

BACKGROUND: Patients with early gastric cancer have an excellent prognosis with low rates of recurrence, but may have an increased risk of developing a second primary cancer. Because the number of early gastric cancers has increased, clarification of both recurrences and second primary cancers is important for the development of effective postoperative follow-up programmes. METHODS: Data on 1070 patients with early gastric cancer were analysed retrospectively with respect to the clinicopathological features of both recurrence and second primary cancers after surgical treatment. RESULTS: Multivariate analysis showed that lymph node metastasis and older age were independent risk factors for recurrence of early gastric cancer. The incidence of second primary cancers was 5.0 per cent; lung and colorectal cancers were detected most frequently, followed by cancers in the oesophagus, breast and remnant stomach. CONCLUSION: Clinicopathological features of patients with early gastric cancer can be used to identify those most at risk of developing either recurrence or a second primary cancer.     

Epidemiological study of oesophageal and gastric cancer in south-east England

BACKGROUND: This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer. METHODS: Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960-1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported. RESULTS: In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change + 0.05 for men, + 0.009 for women). For the gastric cardia, the incidence in males increased (average annual change + 0.025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change + 0.07 for men, + 0.009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes. CONCLUSION: Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes.     

Non-small-cell lung cancer: unusual presentation in the gluteal muscle

Lung cancer is one of the most commonly diagnosed cancers in both men and women worldwide. It is also one of the most common forms of cancer in Ireland, accounting for about 20% of all deaths from cancer each year. Early detection of lung cancer is infrequent, and most cases are not diagnosed and treated until they are at an advanced stage. Distant metastases in lung cancer commonly involve the adrenal glands, liver, bones, and central nervous system; they are only rarely seen in the skeletal system. We report a rare case of metastasis to the gluteal muscle as the initial presentation of lung cancer.     

Colorectal cancer. Some aspects of epidemiology, risk factors, treatment, screening and survival

In developed populations colorectal cancer, which after lung cancer is the commonest of cancers, accounts for up to 6% of all deaths. It occurs most frequently in populations in prosperous industrialised countries, save Japan, and is rare in Third-World populations pursuing a traditional lifestyle. Peak occurrence is in the 7th decade. Colon cancer affects the sexes equally, but males are much more prone to rectal cancer. The precise causation is uncertain. Risk factors include genetic or familial predisposition, inflammatory bowel disease, diet (especially high fat and low dietary fibre intakes), and possibly alcohol intake. Surgery remains the treatment of choice. Stage is by far the most important factor influencing prognosis. Major refinements in both surgical and therapeutic measures have had disappointingly little effect on survival time. Overall median mortality occurs in 1-1 1/2 years; only one-third to one-half of patients survive for 5 years. While effective screening for very early detection could increase survival time, this will result only from further education. Since little avoiding action is practicable, the outlook for patients will remain daunting until help is sought far earlier.     

Operative mortality and five year survival rates in patients with bronchogenic carcinoma

A series of 968 men and 108 women with histologically confirmed lung cancer operated on at twelve teaching hospitals in Philadelphia from 1956 to 1965 were analyzed in regard to operative risk and five year survival rate. Patients who were explored but did not have resection were included in the calculation of rates by age and histologic type of tumor because such patients have a significant operative mortality but no benefit. The operative mortality exceeded the five year survival rate in men aged seventy and over, in patients of both sexes with undifferentiated carcinoma, in patients of both sexes who had exploratory thoracotomy without resection, and in men who had right pneumonectomy. The operative risk was lower and the five year survival rate slightly higher in women than in men.     

Comparative analysis of sentinel lymph node operation in male and female breast cancer patients

BACKGROUND: Male breast cancer accounts for < 1% of breast cancers. Sentinel lymph node (SLN) operation is commonly used in the evaluation of female breast cancer patients. The purpose of this study was to determine whether SLN operation is as feasible and accurate in male patients compared with female patients. STUDY DESIGN: Between 1999 and 2005, 30 men and 2,784 women underwent SLN operation. Clinical and pathologic data were reviewed and statistical analysis performed. RESULTS: Men presented at an older age (p = 0.005) and with larger tumors than women (p = 0.04). The SLN was identified in 100% of men and in 98.3% of women (p = NS). The mean number of SLNs harvested was 3.5 in men and 3.0 in women (p = NS). The incidence of positive SLNs was higher in men (37.0% versus 22.3%), although this did not reach statistical significance (p = 0.1). In patients with a positive SLN there were additional non-SLNs positive in 62.5% of men, compared with 20.7% in women (p = 0.01). The median size of the largest lymph node metastasis was 10 mm in men and 3 mm in women (p = 0.03). CONCLUSIONS: SLN operation in clinically node-negative men is feasible and accurate. Male breast cancer patients present at an older age and with larger tumors than female breast cancer patients. Male patients have higher nodal tumor burden reflected in a larger size of nodal metastasis and increased risk of harboring additional disease in axillary lymph nodes when the SLN is positive. Intraoperative SLN evaluation should be considered in the surgical management of male breast cancer.     

Estimation of the risk of lung cancer in women participating in a population-based breast cancer screening program

IntroductionLung cancer mortality is increasing in women. In Spain, estimates suggest that lung cancer mortality may soon surpass breast cancer mortality, the main cause of cancer mortality among women. The aim of this study was to estimate the proportion of women at high risk of developing lung cancer in a group of participants in a population-based breast cancer screening program.MethodsCross-sectional study in a sample of women who participated in a population-based breast cancer screening program in 2016 in Hospitalet de Llobregat n = 1,601. High risk of lung cancer was defined according to the inclusion criteria of the National Lung Screening Trial (NLST) and the Dutch-Belgian randomized lung cancer screening trial (NELSON).ResultsAround 20% of smokers according to NLST and 40% of smokers according to NELSON criteria, and around 20% of former smokers according to both criteria, are at high risk of developing lung cancer. A positive and statistically significant trend is observed between the proportion of women at high risk and nicotine dependence measured with the brief Fagerström Test.ConclusionsA high proportion of participants in this breast cancer screening program have a high risk of developing lung cancer and would be eligible to participate in a lung cancer screening program. Population-based breast cancer screening programs may be useful to implement lung cancer primary prevention activities.     

Risk of lung cancer among patients with head and neck cancer

A cohort of 5180 patients with head and neck cancer, who were part of the tumor registry of the Surveillance, Epidemiology, and End Results area of western Washington State, was followed up for as many as 15 years to determine the risk of lung cancer. A sample of 522 patients from this cohort was interviewed to determine smoking history. Lung cancer developed in 356 (6.9%) of the 5180 patients. The overall annual incidence of lung cancer remained relatively constant between approximately 1.0% and 2.0% during the 15 years of follow-up. Men had an increased risk of lung cancer compared with women (relative risk [RR] = 1.56; 95% confidence interval [CI] = 1.18 to 2.03). Compared with patients with oral cavity cancer (RR = 1.00), the relative risk of lung cancer developing by the site of the index tumor was 0.63 (95% CI = 0.40 to 0.98) for lip, 1.12 (95% CI = 0.81 to 1.56) for intrinsic larynx, 1.73 (95% CI = 1.21 to 2.47) for oropharynx, 1.84 (95% CI = 1.16 to 2.92) for hypopharynx, and 2.28 (95% CI = 1.60 to 3.24) for extrinsic larynx. Among the 522 patients who were interviewed, men smoked more than women ( p < 0.0001), and patients with laryngeal or pharyngeal cancer smoked more than patients with cancer of the lip or the oral cavity ( p < 0.05). Among patients with head and neck cancer, the risk of lung cancer is highest for men and for patients with cancer of the pharynx or extrinsic larynx. These findings may be explained by differences in smoking consumption. (Otolaryngol Head Neck Surg 1997;116:630-6.)     

Epidemiological fundamentals of clinically localized prostate cancer

Prostate cancer is the sixth most common cancer in the world (in the number of new cases), the third most common cancer in men, and the most common cancer in men in Europe, North America, and some parts of Africa. Different geographical regions have varying incidence and mortality. The risk of prostate cancer is increased by African-American ethnicity, increasing age, positive family history, and other factors such as diet. Nonetheless, the causes of prostate cancer are not well understood compared with other common cancers like lung and breast cancer. The introduction of prostate-specific antigen (PSA) screening made an enormous impact on the incidence of prostate cancer, which increased in the early 1990s and is currently down to pre-PSA screening levels. Screening has caused a change in pattern of disease to an earlier stage but not lower grade. Yet we know little about what causes this disease, in the past 10 years interest in and funding for prostate cancer research have increased and several promising risk modifiers have been identified-eg, genetic predisposition, insulin growth factor (IGF) concentrations, and lycopene consumption.     

Declining mortality from bladder cancer in Europe

OBJECTIVE

To update trends in bladder cancer mortality in 32 European countries and the European Union (EU) as a whole, as mortality from bladder cancer has been declining in most of Western Europe since the early 1990s, but it has still been increasing in several central and eastern European countries up to the mid 1990s.

METHODS

We used data from the World Health Organization (WHO) database over the period 1970–2004. Significant changes in mortality rates were identified using join‐point regression analysis.

RESULTS

In the EU overall (27 countries), bladder cancer mortality rates (age‐standardized, world standard population) were stable up to the early 1990s at ≈ 7/100 000 men and 1.5/100 000 women, and declined thereafter by ≈ 16% in men and 12% in women, to reach values of 6 and 1.3/100,000, respectively, in the early years of the present decade. Over recent years, most countries showed decreasing trends, except Croatia and Poland in both sexes, Romania in men and Denmark in women. Truncated rates at age 35–64 years were lower in both sexes and trends for men were more favourable, with an overall decrease by >21% during the last decade. Join point regression analysis indicates that, for most countries, the trends were more favourable over recent calendar periods.

CONCLUSION

The favourable trends in men are partly or largely due to the recent declines in the prevalence of smoking in European men, together with reduced occupational exposure to occupational carcinogens. The decreases in women are more difficult to explain. Better control of urinary tract infections has probably played a role, while the role of diet and other potential urinary tract carcinogens remains undefined.     

Radical prostatectomy for high-risk prostate cancer

OBJECTIVES: Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. METHODS: We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. RESULTS: Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. CONCLUSION: Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.     

Surveillance for the detection of early lung cancer in patients with bronchial dysplasia

BACKGROUND: The natural history of bronchial preinvasive lesions and the risk of developing lung cancer in patients with these lesions are not clear. Previous studies have treated severe dysplasia and carcinoma in situ (CIS) on the assumption that most will progress to invasive carcinoma. AIMS: To define the natural history of preinvasive lesions and assess lung cancer risk in patients with these lesions. Hypothesis: Most preinvasive lesions will not progress to invasive carcinoma but patients with these lesions will be at high risk. METHODS: A cohort of patients with preinvasive lesions underwent fluorescence bronchoscopy every 4-12 months and computed tomography of the chest annually. The main end point was the development of invasive carcinoma. RESULTS: 22 patients with 53 lesions were followed up for 12-85 months. 11 cancers were diagnosed in 9 patients. Of the 36 high-grade lesions (severe dysplasia and CIS), 6 progressed to invasive cancers. 5 separate cancers developed at remote sites in patients with high-grade lesions. All cancers were N0M0 and curative treatment was given to 8 of the 9 patients. The cumulative risk of developing lung cancer in a patient with a high-grade lesion was 33% and 54% at 1 and 2 years, respectively. Of the 17 low-grade lesions, none progressed to invasive carcinoma. CONCLUSIONS: Although the risk of malignant progression of individual preinvasive lesions is relatively small, patients with high-grade lesions are at high risk of lung cancer. Surveillance facilitated early detection and treatment with curative intent in most patients.     

Gall bladder cancer,extrahepatic bile duct cancer and ampullary carcinoma in New Zealand: Demographics,pathology and survival

Introduction: The aim of present paper was to document the incidence of gall bladder cancer, cancer of the extrahepatic bile ducts and ampullary carcinoma in New Zealand. Methods: Data were collected from the New Zealand Cancer Registry from 1980 to 1997 and combined with national census statistics to give crude and age standardized incidence rates. Results: Over the 18‐year study period, 226 carcinomas of the ampulla of Vater, 608 gall bladder cancers, and 486 extrahepatic cholangiocarcinomas were registered. The age standardized incidence rates for gall bladder carcinoma in all New Zealanders were 0.41/100 000 in men and 0.74/100 000 in women. The age standardized incidence rates for gall bladder cancer in Maori were 1.49/100 000 in Maori men and 1.59/100 000 in Maori women. The corresponding age standardized incidence rates for extrahepatic bile duct cancers were 0.67/100 000 in men and 0.45/100 000 in women. There were insufficient cases to calculate an age standardized incidence in Maori or Pacific Islanders. For carcinoma of the ampulla, the age standardized rates were 0.34/100 000 in men and 0.25/100 000 in women. There were insufficient cases to calculate an age standardized incidence rate for Maori or Pacific Islanders. When histology was defined adenocarcinoma was the most common form of cancer occurring in 66% of gall bladder cancers, 91% of extrahepatic bile duct cancers and 70% of ampullary cancers. Most tumours were advanced at presentation with regional or distant metastases present in 72% of gall bladder cancers, 63% of extrahepatic bile duct cancers and 69% of ampullary tumours at diagnosis. Survival was poor with median survivals of 86 days, 151 days and 440 days recorded for gall bladder cancer, extrahepatic bile duct cancer and ampullary cancer, respectively. Conclusions: The demographic profile, pathology and survival of patients with gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma are similar in New Zealand to that of other Western countries. However New Zealand Maori have a relatively high incidence of gall bladder cancer, and the incidence is equal in both Maori men and women, while cancers of the extra­hepatic bile duct and ampulla of Vater are rare in Maori. In comparison, cancers of the gall bladder, extrahepatic bile ducts and ampulla are rare in Pacific Islanders.     

Prostate cancer detection strategies

Prostate cancer is the most common malignancy in men and, as a result, there has been a nationwide emphasis on screening and detection. With the widespread use of the prostate-specific antigen (PSA), prostate cancer screening effectively detects localized prostate cancer. However, recent reports have identified a significant proportion of prostate cancer in men with low PSA levels. Many of these cancers are higher-grade malignancies. Consequently, PSA may function more effectively as a screening tool when applied over a continuum that is associated with degree of risk, rather than a binary measure. Other markers are currently being investigated. Ideally, a marker will identify the malignancy that is a clinical threat, thereby avoiding intervention for indolent disease. Prevention strategies may be employed for higher-risk patients, and these strategies eventually may be tailored to genetic or other risks.     

Loss of heterozygosity at 3p in benign lesions preceding invasive breast cancer

BACKGROUND: Loss of heterozygosity (LOH) at chromosome 3p is one of the most common genetic abnormalities identified in human cancers and has occasionally been noted in benign proliferative lesions predisposing to breast cancer. If the frequency of LOH at 3p in benign proliferative lesions correlates with the subsequent development of breast cancer, it may be possible to develop powerful tools for molecular risk assessment based on this technology. MATERIALS AND METHODS: Archival paraffin-embedded tissues from benign breast biopsies in five women who have developed breast cancer and three women who have not developed breast cancer were microdissected and allelotyped at 3p using six microsatellite markers. RESULTS: No LOH was detected in the biopsies from women who have not developed breast cancer. For women developing breast cancer, the proportion of informative loci showing LOH in the benign proliferative lesions was 0.47 as compared to 0.57 for the associated breast cancers. There was no LOH detected in epithelial DNA from a fibroadenoma. Of 15 informative loci, 4 (27%) showed LOH in both the benign proliferative lesion and the associated cancer; however, the actual parental allele lost was different in three of these four cases. CONCLUSIONS: These results suggest that there are specific patterns of genetic instability common to preneoplastic lesions and the breast cancers that subsequently develop even when the paired lesions are not clonally related. LOH analysis of benign breast epithelium may provide a tool for molecular risk assessment and a surrogate endpoint for breast cancer chemoprevention trials.     

Family history and the risk of prostate cancer

A case-control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls. Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P less than .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11-fold increased risk of developing prostate cancer. Recognizing that 9-10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease.     

Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom

To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome.     

Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis

BACKGROUND: Individuals with severely impaired lung function have an increased risk of lung cancer. Whether milder reductions in forced expiratory volume in 1 second (FEV(1)) also increase the risk of lung cancer is controversial. Moreover, there is little consensus on whether men and women have similar risks for lung cancer for similar decreases in FEV(1). METHODS: A search was conducted of PubMed and EMBASE from January 1966 to January 2005 and studies that examined the relationship between FEV1 and lung cancer were identified. The search was limited to studies that were population based, employed a prospective design, were large in size (> or = 5000 participants), and adjusted for cigarette smoking status. RESULTS: Twenty eight abstracts were identified, six of which did not report FEV1 and eight did not adjust for smoking. Included in this report are four studies that reported FEV1 in quintiles. The risk of lung cancer increased with decreasing FEV1. Compared with the highest quintile of FEV1 (> 100% of predicted), the lowest quintile of FEV1 (< approximately 70% of predicted) was associated with a 2.23 fold (95% confidence interval (CI) 1.73 to 2.86) increase in the risk for lung cancer in men and a 3.97 fold increase in women (95% CI 1.93 to 8.25). Even relatively small decrements in FEV1 ( approximately 90% of predicted) increased the risk for lung cancer by 30% in men (95% CI 1.05 to 1.62) and 2.64 fold in women (95% CI 1.30 to 5.31). CONCLUSION: Reduced FEV1 is strongly associated with lung cancer. Even a relatively modest reduction in FEV1 is a significant predictor of lung cancer, especially among women.