Showing papers by "David Forman published in 2005"

The Y deletion gr/gr and susceptibility to testicular germ cell tumor

Abstract: Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region—known as the “gr/gr” deletion—has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3–3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5–6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6–5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72–3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.

A Systematic Review and Meta-Analysis of the Sex Ratio for Barrett's Esophagus, Erosive Reflux Disease, and Nonerosive Reflux Disease

Abstract: Barrett's esophagus is associated with reflux disease and substantially increases the risk of esophageal adenocarcinoma. The authors undertook a systematic review and meta-analysis of the sex ratio for Barrett's esophagus, erosive reflux disease (ERD), and nonerosive reflux disease (non-ERD) to compare these results with the sex ratio for esophageal adenocarcinoma. MEDLINE (US National Library of Medicine, Bethesda, Maryland) (1966-2004) and EMBASE (Reed Elsevier PLC, Amsterdam, Netherlands) (1980-2004) were searched for relevant citations with a highly sensitive search strategy. Studies to be included required a sample size of 50 or more patients and consecutive recruitment at an institute accessible by all. Stata, version 8.2, software (StataCorp LP, College Station, Texas) was used to conduct random effects meta-analyses. Excess heterogeneity was investigated by meta-regression. The Barrett's esophagus meta-analysis gave an overall pooled male/female sex ratio of 1.96/1 (95% confidence interval (Cl): 1.77, 2.17/1). For ERD, the pooled male/female sex ratio was 1.57/1 (95% Cl: 1.40, 1.76/1) and, for non-ERD, 0.72/1 (95% Cl: 0.62, 0.84/1). All of these estimates were associated with substantial heterogeneity (I 2 = 81.1%, 92.7%, and 88.8%, respectively). The meta-analysis estimates for ERD and Barrett's esophagus, while showing an excess of males, are substantially lower than similar estimates for esophageal adenocarcinoma. It is important to establish why male Barrett's esophagus and ERD patients are at increased risk of malignancy compared with females.

Ethnicity, Gender, and Socioeconomic Status as Risk Factors for Esophagitis and Barrett's Esophagus

Abstract: Barrett’s esophagus is thought to be a disease occurring predominantly in White Caucasian males of higher socioeconomic status. There are no published studies simultaneously examining risk of Barrett’s esophagus according to ethnicity, gender, and socioeconomic status within a single data set. The authors conducted a retrospective case-control analysis within a cross-sectional study to determine risk of Barrett’s esophagus in relation to sociodemographic variables in a large United Kingdom population. All patients undergoing upper gastrointestinal endoscopy at two clinical centers between January 2000 and January 2003 were evaluated. Data on ethnicity, age, gender, socioeconomic status, and the presence of Barrett’s esophagus and esophagitis at endoscopy were collected. A total of 20,310 patients were analyzed. Barrett’s esophagus was more common in White Caucasians (401/14,095 (2.8%)) than in South Asians (16/5,190 (0.3%)) (adjusted odds ratio (OR) ¼ 6.03, 95% confidence interval (CI): 3.56, 10.22), as was esophagitis (2,500/14,095 (17.7%) vs. 557/5,190 (10.7%); adjusted OR ¼ 1.76, 95% CI: 1.57, 1.97). Patients with Barrett’s esophagus were also more likely to be male (adjusted OR ¼ 2.70, 95% CI: 2.18, 3.35) and of higher socioeconomic status (adjusted OR ¼ 1.58, 95% CI: 1.16, 2.15 (top tertile vs. bottom tertile)). White Caucasian ethnicity, male gender, and higher socioeconomic status are independent risk factors for Barrett’s esophagus. Barrett esophagus; esophagitis; ethnicity; social class

No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARdelta and PPARgamma act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma.

Abstract: Objectives Regular continuous non-steroidal anti-inflammatory drug (NSAID) use has been associated with a reduction in risk of colorectal cancer. Our objective was to investigate whether or not a number of the polymorphic genes involved in the metabolism of NSAIDs, including cytochrome P450 s (CYPs), act as modifiers of this protective effect. Methods As part of a multi-centre case-control study, 478 colorectal cancer patients and 733 controls (433 matched case-control pairs) answered questions on NSAID use. These individuals were then genotyped for common polymorphisms in P450 CYP2C8, P450 CYP2C9, UDP-glucuronosyl transferase (UGT)1A6 and peroxisome proliferator-activated receptor isoforms delta and gamma (PPARdelta and PPARgamma). Results and conclusion Our study confirmed the reduction in risk of colorectal cancer with regular NSAID use (odds ratio (OR) = 0.73, 95% confidence interval (CI) (0.56, 0.95)) but showed that none of the polymorphic genes studied appeared to modify the protective effect of regular NSAID use.

The long term survival of rectal cancer patients following abdominoperineal and anterior resection: results of a population-based observational study.

Abstract: Aims The surgical management of rectal cancer is not uniform. Both abdominoperineal (APR) and anterior resection (AR) are used in potentially curative surgery but there is no definitive evidence regarding comparative survival outcomes and no randomised controlled trials. We sought to determine if any differences in survival existed between patients who received AR or APR. In addition, we sought to determine how variations in surgical management relate to the degree of specialisation and caseload of the managing consultant. Patients and methods A retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service was undertaken. All patients (3521) diagnosed with rectal cancer in the former Yorkshire Regional Health Authority (population 3.6 million) between 1986 and 1994 who received either an APR or AR were included. Survival was assessed in relation to the surgical methods adopted. In addition, we determined whether the extent of specialisation of the managing consultant influenced the type of operation adopted. Results A Log Rank test, stratified for sex and age, showed a statistically significant 6.7% 5-year survival advantage for patients receiving AR ( p =0.0064). AR was more likely to be performed by more specialist colorectal cancer surgeons ( p Conclusions This evidence suggests that the outcomes of the two main surgical procedures used in curative surgery for rectal cancer are different and that, when possible, AR should be the operation of choice. Our results show no indication of excess risk associated with this procedure compared with APR.

The association between Helicobacter pylori infection and adult height

Abstract: Objectives: A cross-sectional survey was performed to evaluate the association between H. pylori and adult height. Methods: H. pylori infection was assessed using a 13C-urea breath test and height measured by a research nurse using a stadiometer in participants between the ages of 40–49 years. Results: Height was measured in 2932/3682 participants that attended and were evaluable. H. pylori infected women were 1.4 cm shorter than uninfected women (95% confidence interval, CI=0.7–2.1 cm) and this statistically significant difference persisted after adjusting for age, ethnicity, childhood and present socio-economic status (H. pylori positives 0.79 cm shorter; 95%CI: 0.05–1.52 cm). H. pylori positive men were 0.7 cm shorter than uninfected men but this did not reach statistical significance (95% CI: −0.1–1.5 cm). Conclusion: Although H. pylori infection is associated with reduced adult height in women, this maybe due to residual confounding.

Re: The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence.

Abstract: Pohl and Welch consider whether the reported dramatic increase in esopha-geal adenocarcinoma represents a real increase in disease burden or whether it can be explained by artifacts introduced by classifi cation problems and/or increased diagnostic intensity (1). Based on an analysis of the National Cancer In stitute's Surveillance, Epidemiology and End Results (SEER) database, they conclude that the observed increase not only represents a true increase in disease but also that the rate of increase makes this cancer \" the fastest rising malig-nancy in the United States. \" They show an approximate sixfold increase in incidence between 1973–1975 and 1999– 2001, a rate substantially higher than that for other cancers known to be increasing in incidence (e.g., two-to threefold increa ses for melanoma and prostate cancer). The authors dismiss reclassifi cation of gastric cardia adenocarcinoma as an arti-factual explanation for the increase in esophageal adenocarcinoma because incidence of the former is also increasing over time and, they argue, if the reclassi-fi cation were to explain the increase in esophageal adenocarcinoma, cardia adenocarcinoma incidence should decrease. This is true if the entirety of the increase were to occur through reclassifi-cation, but changes over time in the approach to cardia adenocarcinoma clas-sifi cation could profoundly affect the magnitude of the increase in cancers in this region of the body. The esophagus and cardia are anatomically juxtaposed, and their respective tumors cannot be distinguished by microscopic pathology. It can be diffi cult, and sometimes impossible, to assign many tumors unambiguously to the stomach or the esophagus. After the growth in interest in esophageal adenocarcinoma, it is also likely that a potential bias is operating, such that, given uncertainty, surgeons and gastroenterologists may have become increasingly more prone to assign tumors at the gastroesophageal junction to the esophagus. When making comparisons over time using routinely acquired data, it is prudent to combine results for adenocarcinoma at both the gastric cardia and the esophagus. By combining, the sixfold increase reported by Pohl and Welch between 1975 and 2001 reduces to less than threefold. Pohl and Welch also fail to take into account overall trends in gastric cancer incidence, especially those for which subsite information is unavailable. Fig. 1 shows, using the same SEER data (2) and the same time period considered by Pohl and Welch, trends in gastric adenocarci-noma incidence separately for the cardia, other specifi ed subsites, and unspecifi ed for subsite. The most …

Site-specific occurrence of nonmelanoma skin cancers in patients with cutaneous melanoma

Abstract: In a registry-based case–control study, we compared the site-specific occurrence of nonmelanoma (keratinocytic) skin cancers among patients with cutaneous melanoma cases (cases, n=3774) and solid tumours (controls, n=349 923), respectively. Overall, patients with melanoma were almost five-fold more likely to develop keratinocytic cancers compared with solid tumour controls (adjusted OR 4.7, 95% CI 4.1–5.3), but the risks varied depending upon the site of melanoma. Whereas patients with melanoma of the head and neck had similarly increased risks of keratinocytic cancers across all body sites, patients with melanoma of the trunk were significantly more likely to develop keratinocyte cancer diagnosed on the trunk (adjusted OR 12.5, 95% CI 7.2–20.2) than on the head and neck (adjusted OR 3.0, 95% CI 2.2–4.3). Similar colocalisation of skin tumours was observed for patients with melanomas of the lower limb. These findings provide support for the hypothesis that skin cancers at different anatomical sites may arise through different causal pathways.

Is the rate of biological aging, as measured by age at diagnosis of cancer, socioeconomically patterned?

Abstract: Study objective: To investigate the hypothesis that biological aging, as measured by age at diagnosis of some common cancers, is socioeconomically patterned. Design: A cross sectional analysis of the association between an area based measure of material deprivation and age at diagnosis of four common cancers (breast, prostate, colorectal, and lung cancers). A further analysis, restricted to breast and colorectal cancer, adjusted for stage and grade of cancer at diagnosis. Setting: The Northern and Yorkshire cancer registry and information service, Northern and Yorkshire region, UK. Participants: All people living in the Northern and Yorkshire region diagnosed with breast, prostate, colorectal, or lung cancer in 1986–1995. All people living in the Northern and Yorkshire region diagnosed with breast or colorectal cancer in 1998–2000 with data on stage and grade of cancer at diagnosis. Main results: There was evidence that greater material deprivation was associated with younger age at diagnosis of cancer in prostate (s coefficient –0.073), colorectal (women: –0.042; men: –0.063), and lung cancer (women: –0.214; men: –0.161). The opposite association was found in women with breast cancer (0.149). Adjusting for stage and grade at incidence, where possible, had little effect on the magnitude of the s coefficients. Conclusions: Age at diagnosis of some common cancers seems to be socioeconomically patterned with people from more deprived areas being diagnosed with prostate, colorectal, and lung cancers earlier in life. The opposite was seen in women with breast cancer. Further work is required to investigate the socioeconomic distribution of more accurate measures of biological aging.