Aspirin protects against gastric cancer: results of a case-control study from Moscow, Russia.

A case-control study of stomach cancer which includes 448 cases and 610 hospital controls has been conducted in Moscow, Russia. Information on life-style habits, such as smoking, alcohol consumption, diet, medical history and use of different medications including aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) was collected using a self-administered structured questionnaire. Venous blood was drawn from 361 cases and 441 controls. A serological test for Helicobacter pylori immunoglobulin G was performed to detect infected individuals. Use of aspirin and other NSAIDs was associated with protection against cancer of the stomach (OR = 0.60, 95% CI 0.41-0.90). Analysis by subsite revealed that aspirin did not affect the risk of cancer of the gastric cardia but had a protective effect for non-cardia gastric cancer. The OR associated with use of aspirin adjusted for age and education for both sexes combined was 0.49 (95% CI 0.31-0.77). A decrease in relative risk was statistically significant for men (OR = 0.48, 95% CI 0.25-0.92) and women (OR = 0.52, 95% CI 0.28-0.97). Controlling for major risk factors did not attenuate the reduction in risk. The observed associations were also present in individuals who were H. pylori immunoglobulin G-positive. There was no reduction in risk associated with aspirin and/or non-aspirin NSAIDs among non-infected subjects.     

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.     

Family history of cancer and risk of esophageal and gastric cancers in the United States

The worldwide rates for histology- and subsite-specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high-incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population-based, case-control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261) or non-cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91-1.97] and non-cardia segments (OR =1.46, 95% CI 1.03-2.08). This familial tendency, particularly for non-cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50-4.23). In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07-2.83) and non-cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09-2.82). Also seen were non-significant familial associations of esophageal squamous-cell cancer with prostate cancer as well as non-cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States.     

Decreasing incidence of both major histologic subtypes of gastric adenocarcinoma--a population-based study in Sweden

While the overall incidence of gastric cancer has fallen, presumably to a large extent in parallel with Helicobacter pylori infection, the occurrence of the diffuse histologic type is thought to have remained more stable, questioning the aetiologic role of H. pylori. We have analysed the incidence of the intestinal and diffuse types separately, while considering subsite (cardia/non-cardia). With an extensive prospective effort we identified all incident cases of gastric adenocarcinoma (n = 1337) in a well-defined Swedish population (1.3 million) 1989-1994. Tumours were uniformly classified histologically and topographically. Subgroup-specific incidence rates were computed and modelled using multivariate logistic regression. Site-specific trends were clearly discrepant. The overall incidence of adenocarcinoma distal to the gastric cardia declined by 9% (95% confidence interval 6-12%) per year, while cardia cancer remained stable. Thus, the feared rise in cardia cancer could not be confirmed despite clear site-specific trend discrepancies. The intestinal type predominated, especially in high-risk areas, while diffuse tumours prevailed among young patients and women. Both main histologic types of gastric adenocarcinoma declined markedly, at similar rapidity, and with no significant trend differences between the intestinal and diffuse types, even after multivariate adjustments. Our results are consistent with an aetiologic role of environmental factors including H. pylori also for diffuse-type gastric cancers.     

Parity and risk of stomach cancer by sub-site: a national Swedish study

We investigated stomach cancer risk by anatomic sub-site in relation to parity, as a marker for higher exposure to sex hormones, in a case-control study, nested within a cohort of 2,406,439 Swedish women born in 1925 or later and followed from 1970 or age 30 until emigration, death, any cancer diagnosis, or through 2004, whichever occurred first. We identified 286 cardia and 2498 non-cardia stomach cancer cases with five matched controls for each case. Cross-linkage with the Multi-Generation Register provided information about reproductive history. Using conditional logistic regression models for estimating odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for education level and occupation, we found no association between any aspect of parity and non-cardia stomach cancer (OR=1.01, 95% CI 0.89-1.15, comparing parous with nulliparous women). However, a 30% risk reduction for postmenopausal cardia cancer (OR=0.7, 95% CI 0.4-1.0) was noted among parous relative to nulliparous women and the risk for premenopausal cardia cancer fell with increasing number of children (P for trend=0.04). Our results indicate that exposure to female sex hormones does not protect against non-cardia stomach cancer and does not explain male predominance. The observed moderate inverse relationship between parity and cardia cancer may be mediated by non-hormonal factors and warrants further study.     

Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus.

Several studies indicate that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric corpus and possibly gastric cardia cancers. The best known action of NSAIDs is to block the enzyme cyclooxygenase, the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins. We investigated the expression of cyclooxygenase-2 (Cox-2) in adenocarcinomas of the gastric cardia (N=19) and corpus (N=15) and in adjacent normal epithelium from a high risk Chinese population. Immunohistochemical detection of Cox-2 revealed positive staining in 36% of the gastric cardia cancer cases and 60% of the gastric corpus cancer cases, whereas histologically normal tissue from the same patients were negative. Smooth muscle, stroma and inflammatory cells were also positive. Our results suggest that Cox-2 is overexpressed in a large proportion of adenocarcinomas of the gastric corpus and in a smaller number of gastric cardia cancer cases.     

Fruit and vegetable consumption and gastric cancer by location and histological type: case-control and meta-analysis.

The available information favours a greater impact of environmental exposures on intestinal type gastric cancer, and risk factors for the cardia and distal stomach cancers also appear to be different. We aimed to estimate the association between fruit and vegetable intake and gastric cancer, by location and histological type. We performed a population-based case-control study and a meta-analysis of studies addressing this issue. Incident cases (n=305) were identified in two large teaching hospitals (Porto, Portugal), and controls were randomly sampled among city dwellers (n=1129). Published studies were searched through PubMed, and effects were combined with random effects meta-analysis. In our case-control study, the odds ratio (OR) for the comparison of the highest vs. lowest tertile of fruit consumption was 0.47 [95% confidence interval (CI): 0.21-1.05] for cardia, 0.53 (95% CI: 0.35-0.80) for non-cardia cancer, 0.36 (95% CI: 0.20-0.62) for intestinal, and 1.00 (95% CI: 0.53-1.90) for the diffuse histological type. For vegetables, the corresponding OR was 0.59 (95% CI: 0.26-1.35), 0.85 (95% CI: 0.58-1.26), 0.95 (95% CI: 0.57-1.57), and 0.60 (95% CI: 0.32-1.14). In meta-analysis, considering fruit consumption (highest vs. lowest category), the combined OR was 0.58 (95% CI: 0.38-0.89) for cardia, 0.61 (95% CI: 0.44-0.84) for non-cardia, 0.49 (95% CI: 0.33-0.72) for intestinal type, and 0.82 (95% CI: 0.57-1.20) for diffuse type. Vegetables also decreased the risk of cardia (OR=0.63, 95% CI: 0.50-0.79), non-cardia (OR=0.75, 95% CI: 0.59-0.95), intestinal (OR=0.61, 95% CI: 0.44-0.86), and diffuse type (OR=0.67, 95% CI: 0.44-1.01). Fruit or vegetable intake was associated with a decreased risk of gastric cancer regardless of the anatomical location and the histological type, although dietary intake had a more clear-cut protective effect on intestinal type cancers.     

Association between nonsteroidal anti-inflammatory drug use and the incidence of lung cancer in the Iowa women's health study.

BACKGROUND: Previous studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of lung cancer, but the data are inconsistent and are limited particularly with respect to the effects of aspirin, separate from other NSAIDs. METHODS: The Iowa Women's Health Study is a prospective cohort of 41,836 Iowa women ages 55 to 69 years old at baseline in 1986. NSAID use was assessed in 1992. Over 10 years of follow-up, 403 incident cases of lung cancer were identified. The association of incident lung cancer with current use of aspirin or non-aspirin NSAIDs was analyzed after adjustment for lung cancer risk factors. Hazard ratios (HR) were estimated using multivariate COX proportional hazards regression. RESULTS: There were 27,162 women in the analytic cohort. After controlling for age, education, alcohol intake, pack-years, smoking status, body mass index, and total fruit intake, the RR of women taking six or more aspirin weekly was 1.21 (95% confidence interval, 0.92-1.59). The HR was 1.23 for women taking six or more non-aspirin NSAIDs weekly (95% confidence interval, 0.92-1.65). There was no statistically significant trend by frequency of use for either aspirin (P(trend) = 0.22) or non-aspirin NSAIDs (P(trend) = 0.53). Analyses by histologic type and smoking status yielded similar null results. Information on dosage and duration of use were not available for this analysis. CONCLUSION: These findings do not suggest that aspirin or other NSAIDs reduce risk of lung cancer in this cohort of postmenopausal women.     

Prospective study of serum selenium levels and incident esophageal and gastric cancers

BACKGROUND: From March 1986 through May 1991, we conducted a randomized nutritional intervention trial, the General Population Trial, in Linxian, China, a region with epidemic rates of squamous esophageal and adenomatous gastric cardia cancers. We found that participants who received selenium, beta-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. In the current study, we examined the relationship between selenium levels measured in pretrial (1985) sera from participants and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers during the trial. METHODS: This study was designed and analyzed in accord with a stratified case-cohort sampling scheme, with the six strata defined by sex and three age categories. We measured serum selenium levels in 590 case subjects with esophageal cancer, 402 with gastric cardia cancers, and 87 with gastric non-cardia cancers as well as in 1062 control subjects. Relative risks (RRs), absolute risks, and population attributable risk for cancers were estimated on the basis of the Cox proportional hazards models. All statistical tests are two-sided. RESULTS: We found highly significant inverse associations of serum selenium levels with the incidence of esophageal (P: for trend <10(-4)) and gastric cardia (P: for trend <10(-6)) cancers. The RR and 95% confidence interval (CI) for comparison of highest to lowest quartile of serum selenium was 0.56 (95% CI = 0.44-0.71) for esophageal cancer and 0.47 (95% CI = 0.33-0.65) for gastric cardia cancer. The population proportion of these cancers that is attributable to low selenium levels was 26.4% (95% CI = 14.45-38.36). We found no evidence for a gradient of serum selenium associated with incidence of gastric non-cardia cancer (P: for trend =.96), with an RR of 1.07 (95% CI = 0.55-2.08) for the highest to lowest quartile of serum selenium. CONCLUSIONS: Our study supports findings from previous prospective studies and randomized trials that variations in selenium levels affect the incidence of certain cancers. In the United States, where intervention trials of selenium are in the planning stages, consideration should be given to including populations at high risk for squamous esophageal and gastric cardia cancers.     

Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer.

OBJECTIVE: Previous epidemiological studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of breast cancer, but some studies have been limited in their ability to separate the effects of aspirin from other NSAIDs or to account for breast cancer risk factors. METHODS: We examined the incidence of breast cancer in association with self-reported aspirin, as well as other nonaspirin NSAID use in a large prospective cohort of postmenopausal women (n = 27,616). Over 6 years of follow-up, 938 incident breast cancers were identified. RESULTS: After adjustment for other breast cancer risk factors, any current use of aspirin or other NSAIDs compared with no use was associated with a reduction in risk of breast cancer [relative risk (RR) = 0.80, 95% confidence interval (CI) 0.67-0.95]. There was a trend of decreasing risk of incident breast cancer with increasing frequency of aspirin use (P(trend) = 0.0011). The multivariate-adjusted RR of breast cancer was 0.71 (95% CI 0.58-0.87) for women who reported using aspirin six or more times per week compared with women who reported no use. These results did not depend on whether women had early or late stage breast cancer. No association was found between nonaspirin NSAID use and incident breast cancer. The adjusted RR of using other NSAIDs six or more times per week compared with no use was 1.01 (95% CI 0.83-1.25). CONCLUSION: This prospective study corroborates other reports that use of aspirin might reduce risk of breast cancer.     

Age-associated increase of codon 72 Arginine p53 frequency in gastric cardia and non-cardia adenocarcinoma.

PURPOSE: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility and prognosis. To examine the role of the polymorphism in the gastric adenocarcinoma, we examined 397 patients with or without the cancer. EXPERIMENTAL DESIGN: DNA samples were extracted from archived gastric tumor tissues and/or normal tissues of gastric adenocarcinoma and noncancer patients. The TP53 codon 72 genotypes were determined by PCR-RFLP. RESULTS: The overall genotype frequencies for Pro/Pro, Arg/Pro, and Arg/Arg were 7.3, 45.1, and 47.6%, respectively. A significant stepwise increased frequency of codon 72 Arg p53 with age was observed in patients with gastric cancer, but not in noncancer patients (P = 0.01). Patients with gastric cardia cancer had a significantly higher frequency of homozygous Arg allele than those with non-cardia tumors (P = 0.03) or than noncancer patients. After adjustment for age and gender, a logistic regression analysis suggested that the risk for a p53 Arg homozygous patient to develop cardia cancer is 3.1 95% confidence interval, 1.4-7.3) times greater than for p53 Pro homozygous and p53 Arg/Pro heterozygous patients. No close relationship was observed among patient gender, tumor histological type, p53 protein expression, and codon 72 genotype distribution. CONCLUSIONS: These findings indicate that codon 72 Arg p53 may be associated with a prolonged survival for patients who have had gastric adenocarcinoma, especially non-cardia adenocarcinoma. It may confer, however, a different role on patients who suffer cardia gastric adenocarcinoma.     

Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma

Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.     

Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression

A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case–control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined whether the risk associated with cigarette smoking, body mass index (BMI), gastroesophageal reflux disease (GERD), and non-steroidal anti-inflammatory drug (NSAID) use varied by P53 overexpression. We defined P53 overexpression through immunohistochemistry of paraffin-embedded tumor tissues, using cutpoints based on percent of cells positive. Polytomous logistic regression was used to assess differences between each case group (defined by tumor subtype and P53 expression) and the control group by risk factors. The proportion of cases overexpressing P53 by tumor subtype was 72% for esophageal adenocarcinoma, 69% for gastric cardia adenocarcinoma, 52% for non-cardia gastric adenocarcinoma, and 67% for esophageal squamous cell carcinoma. For most tumor subtypes, we found little difference in risk factors by tumor P53 overexpression. For non-cardia gastric cancer however, an association with cigarette smoking was suggested for tumors that do not overexpress P53, whereas larger BMI was related to adenocarcinomas that overexpress P53 versus no overexpression. Overall, this study did not find a clear relationship between P53 protein overexpression and the known risk factors for subtypes of esophageal and gastric cancers. Further research on these tumors is needed to identify molecular markers associated with variations in the risk factor profiles.     

Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway.

INTRODUCTION: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce risk of colorectal cancer. Although inhibition of cyclooxygenase (COX)-2 is generally thought to be the relevant mechanism, aspirin-like drugs apparently are involved in other pathways and mechanisms. We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer. METHODS: Genetic polymorphisms of five genes identified as being involved in an insulin-related pathway were genotyped using data collected in a case-control study of 1346 incident colon cancer cases and 1544 population-based controls and 952 incident rectal cancer cases and 1205 controls. Genotypes assessed were the 3' untranslated region poly(A) and the intron 8 BsmI polymorphisms of the VDR gene, a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the Gly972Arg polymorphism of the IRS1 gene, and the Gly1057Asp polymorphism of the IRS2 gene. RESULTS: Use of aspirin and NSAIDs was associated with a decreased risk of colorectal cancer, with slightly greater protection from NSAIDs than aspirin for rectal cancer. We observed a significant interaction between IRS1 genotype and aspirin/NSAIDs use and risk of colorectal cancer. Relative to the GR/RR IRS1 genotype, a protective effect from the GG IRS1 genotype was seen in those who did not use NSAIDs; use of NSAIDs was protective for all genotypes. These associations were especially strong for those diagnosed prior to age 65 (P interaction = 0.0006). We also observed a significant interaction between aspirin/NSAIDs use and the VDR gene. Having the SS or BB VDR genotypes reduced risk of colorectal cancer among non-aspirin/NSAID users; however, aspirin/NSAIDs reduced risk for all VDR genotypes. CONCLUSIONS: These data support the protective effect of aspirin and NSAIDs on colorectal cancer risk. In addition, the observed interactions for aspirin/NSAIDs and IRS1 and VDR genotypes suggest that mechanisms other than COX-2 inhibition may be contributing to the protective effect of aspirin and NSAIDs on colorectal cancer risk.     

Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer

Laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit pancreatic cancer, but epidemiologic data to support this finding are limited. We conducted a prospective study from 1992 through 1999 among 28 283 postmenopausal women who lived in Iowa to examine the association between the self-reported use of aspirin and other NSAIDs and the incidence of pancreatic cancer. Eighty incident cases of pancreatic cancer were identified during 7 years of follow-up. The multivariate-adjusted relative risk of pancreatic cancer associated with any current use of aspirin versus no use was 0.57 (95% confidence interval = 0.36 to 0.90). There was a trend of decreasing risk of pancreatic cancer incidence with increasing frequency of aspirin use per week (P(trend) =.005). Nonaspirin NSAID use was not associated with incident pancreatic cancer. These data indicate that aspirin might be chemopreventive for pancreatic cancer.     

A rising trend of gastric cardia cancer in Gansu Province of China

We evaluated the incidence, age, gender, and anatomical distribution of gastric cancers in 65,284 cases of upper GI endoscopies. A total of 5253 gastric cancer cases were identified. Cancers of the cardia, fundus, body and antrum account for 33.6%, 2.7%, 23.6% and 34.0% of all cases, respectively. The mean age for gastric cancers was 56.9 ± 10.2 years and 69.7% of the cancer cases were found in the 50–69 year age group. Subjects with cardia cancer were slightly older than subjects with non-cardia cancer. Over the 12-year period, the incidence of the gastric antrum cancer had significantly declined, whereas the incidence of the gastric cancer in the cardia and body had risen steadily. Thus, there was a rising trend of cardia cancers and a decreasing trend of most non-cardia cancers.     

Prospective study of tooth loss and incident esophageal and gastric cancers in China

Objective: To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study. Methods: Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases. Results: Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1–1.6) in the esophagus, 1.3 (1.0–1.6) in the gastric cardia, and 1.8 (1.1–3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort. Conclusions: In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines.     

Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for > or =60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for > or =60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (> or =30 pills per month for > or =5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.     

Dosage,duration and timing of nonsteroidal antiinflammatory drug use and risk of prostate cancer

Experimental studies suggest that NSAIDs could reduce prostate cancer risk. Results of observational studies on the relation between NSAIDs and prostate cancer risk have, however, been inconsistent. Moreover, none has addressed the issues of dosage, duration and timing of exposure. In a population-based, age-matched case-control study, we measured the association between prostate cancer risk and NSAIDs defined in terms of mean daily dose, cumulative duration and timing of exposure. Eight-year drug exposure history was obtained from the Quebec health insurance system database. Parallel analyses were performed for aspirin and NSAIDs other than aspirin. We controlled for detection bias and assessed the potential impact of protopathic bias. Analyses were performed with conditional logistic regression. Among the 2,221 cases and 11,105 controls, there was a negative trend between cumulative duration of aspirin use and prostate cancer risk (p = 0.0009). Also, exposure to a mean daily dose of aspirin of at least 80 mg, maintained throughout the entire 8 years of follow-up, was associated with an 18% reduction in prostate cancer risk (OR = 0.82, 95% CI 0.71-0.95). In more recent users of such a dose, the risk reduction was 7%. However, 1 year after the end of a 7-year regular aspirin exposure, no residual protective effect persisted. No association was observed between prostate cancer risk and exposure to NSAIDs other than aspirin. The results suggest that long-term and regular use of aspirin, at a dosage beneath that usually recommended for an anti-inflammatory effect, may prevent prostate cancer.     

Association Analysis of Common Genetic Variations in MUC5AC Gene with the Risk of Non-cardia Gastric Cancer in a Chinese Population

Several lines of evidence suggest that genetic variation in MUC5AC gene might contribute to the risk of gastriccancer. We conducted a case-control study to evaluate the relationship between common genetic variations inMUC5AC gene and non-cardia gastric cancer using an LD-based tagSNP approach in Baotou, north-westernChina. We genotyped 12 tagSNPs by TaqMan method among 288 cases with non-cardia gastric cancer and 281normal controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidenceintervals (CIs) for non-cardia gastric cancer risk in association with alleles, genotypes and haplotypes. Weobserved that the frequencies of rs3793964 C allele and rs11040869 A allele were significantly lower in cases thanin controls. Meanwhile, minor allele homozygotes of rs3793964 and rs11040869 were significantly associated witha decreased risk of non-cardia gastric cancer when compared with their major allele homozygotes. Furthermore,a statistically significantly protective effect of rs885454 genotypes on non-cardia gastric cancer was also observed(for CT vs. CC: OR=0.581, 95%CI=0.408-0.829; for CT/TT vs. CC: OR=0.623, 95%CI=0.451-0.884). Our resultsindicated that some common genetic variations in the MUC5AC gene might have effects on the risk of non-cardiagastric cancer in our studied population.