Background & Aims

Epstein-Barr virus (EBV) has been causally associated with cancer; some gastric carcinomas have a monoclonal EBV genome in every cancer cell, indicating that they arose from a single infected progenitor cell. However, the proportion of EBV-positive gastric carcinomas is uncertain and the etiological significance is unknown.

Methods

We conducted a meta-analysis of 70 studies including 15,952 cases of gastric cancer assessed by in situ hybridization for EBV-encoded small RNA.

Results

The pooled prevalence estimate of EBV-positivity was 8.7% (95% CI: 7.5, 10.0) overall, with a two-fold difference by sex: 11.1% (95% CI: 8.7, 14.1) of gastric cancer cases in males vs. 5.2% (95% CI: 3.6, 7.4) of cases in females. Tumors arising in the gastric cardia (13.6%) or corpus (13.1%) were more than twice as likely to be EBV-positive as those in the antrum (5.2%; p<0.01 for both comparisons). EBV-prevalence was four times higher (35.1%) for tumors in post-surgical gastric stump/remnants. Over 90% of lymphoepithelioma-like carcinomas were EBV-positive but only 15 studies reported any cases of this type; prevalence did not significantly differ between the more common diffuse (7.6%) and intestinal (9.5%) histologies. EBV-prevalence was similar in cases from Asia (8.3%), Europe (9.2%), and the Americas (9.9%).

Conclusions

EBV-positive gastric cancers greatly differ from other gastric carcinomas based on sex, anatomic subsite, and surgically disrupted anatomy, indicating that it is a distinct etiologic entity. Epidemiologic studies comparing EBV-positive and -negative gastric cancers are warranted to investigate EBV’s role in gastric carcinogenesis.

Background

Oesophageal cancers rank as the eighth most common cancer and the sixth most common cause of cancer death, worldwide. Gastric atrophy, as determined by a low serum pepsinogen I/II ratio, may be associated with an increased risk of oesophageal squamous cell carcinoma (OSCC). Ghrelin, a hormone which, like pepsinogen, is produced in the fundic glands of the stomach, may be a sensitive and specific marker of gastric atrophy, but its association with OSCC is not known.

Methods

To examine the relationship between baseline serum ghrelin concentration and subsequent risk of OSCC, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. 82 cases of OSCC were matched (1:1) by age and date of blood draw to controls from the ATBC study. Serum ghrelin was measured by radioimmunoassay. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression with adjustment for potential confounders.

Results

For those individuals in the lowest quartile of serum ghrelin, compared to those in the highest, the multivariate odds ratio of subsequent OSCC was 6.83 (95% CI: 1.46, 31.84). These associations were dose dependent (P for trend = 0.005 for both), and independent of the effects of low pepsinogen I/II ratio (a marker of gastric fundic atrophy) and Helicobacter pylori infection. The significance of these associations remained even for individuals developing OSCC up to 10 years after baseline ghrelin measurement, though they become attenuated after 10 years.

Conclusion

Lower baseline concentrations of serum ghrelin were associated with an increase in risk of OSCC. Further studies are needed to confirm this finding in other populations and to explore the role of ghrelin in the aetiology of OSCC.

Background and Aims

Recent observational and genetic studies suggest that some hyperplastic polyps may be associated with increased risk of colorectal cancer. Prospective information on the risk of adenoma recurrence associated with hyperplastic polyps is limited. We sought to investigate whether the coexistence of hyperplastic polyps with adenomatous polyps increases the risk of adenoma recurrence.

Methods

We used multiple unconditional logistic regression models to examine the association between baseline hyperplastic polyps and subsequent adenoma recurrence during a three-year follow up, among 1,637 participants in the Polyp Prevention Trial.

Results

A total of 437 participants (26.7%) had hyperplastic polyps coexisting with adenomas at baseline. Of these, 132 (30.2%) had at least one hyperplastic polyp in the proximal colon while 305 (69.8%) had only distal hyperplastic polyps. When compared with subjects without any hyperplastic polyps at baseline, there was no statistically significant association between presence of baseline hyperplastic polyps and recurrence of any adenoma, OR 1.19 (95% CI: 0.94–1.51) or advanced adenoma, OR 1.25 (95% CI: 0.78–2.03). Also, there was no association between hyperplastic polyp location and adenoma recurrence: OR 1.01 (95% CI: 0.69–1.48) for any proximal hyperplastic polyp and OR 1.26 (95% CI: 0.96–1.65) for distal hyperplastic polyps.

Conclusions

The coexistence of hyperplastic polyps with adenomas, irrespective of location, does not confer an increased risk of adenoma recurrence beyond that of adenomatous polyps alone within three years of follow-up. Prospective long-term studies on adenoma recurrence risk associated with hyperplastic polyps in screening populations are needed.

OBJECTIVES

Osteosarcoma typically occurs during puberty. Studies of the association between height and/or birth-weight and osteosarcoma are conflicting. Therefore, we conducted a large pooled analysis of height and birth-weight in osteosarcoma.

METHODS

Patient data from 7 studies of height, and 3 of birth-weight were obtained, resulting in 1067 cases with height and 434 cases with birth-weight data. We compared cases to the 2000 US National Center for Health Statistics Growth Charts by simulating 1000 age and gender matched controls per case. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between height or birth-weight and risk of osteosarcoma for each study were estimated using logistic regression. All of the case data were combined for an aggregate analysis.

RESULTS

Compared to average birth-weight subjects (2665–4045g), individuals with high birth-weight (≥4046g) had an increased osteosarcoma risk (OR 1.35, 95%CI 1.01–1.79). Taller than average (51st–89th percentile) and very tall individuals (≥90th percentile) had an increased risk of osteosarcoma (OR 1.35, 95%CI 1.18–1.54, and OR 2.60, 95%CI 2.19–3.07, respectively; Ptrend <0.0001).

CONCLUSIONS

This is the largest analysis of height at diagnosis and birth-weight in relation to osteosarcoma. It suggests that rapid bone growth during puberty and in utero contributes to OS etiology.

Background

Cancers of the upper gastrointestinal tract remain a significant cause of morbidity and mortality. Cysteine, known to be involved in a myriad of immuno-modulatory, anti-oxidant, and anti-carcinogenic pathways, has not been investigated in the aetiology of oesophageal or gastric cancers. To examine the relationship between serum cysteine concentration and risk of these cancers we conducted a nested case-cohort study within the General Population Nutrition Intervention Trial in Linxian, China.

Methods

498 oesophageal squamous cell carcinomas (OSCC) and 255 gastric cardia adenocarcinomas (GCA) were matched by age and sex to 947 individuals from the wider cohort. We calculated hazard ratios (HR) and 95% confidence intervals (95% CI) using the case-cohort estimator for the Cox proportional hazards models, stratified on age and sex, with adjustment for potential confounders.

Results

Higher concentrations of serum cysteine were significantly associated with a lower risk of both OSCC and GCA. For those in the highest quartile of serum cysteine, compared to those in the lowest, the multivariate HRs were 0.70 for OSCC (95% CI: 0.51, 0.98) and 0.59 for GCA (95% CI: 0.38, 0.91). These associations were dose dependent (P for trend = 0.006 and 0.008, respectively). These inverse associations were not significantly modified by other risk factors, with the exception of age, where a stronger association was noted among persons in the older age strata.

Conclusion

Higher serum concentrations of cysteine were associated with a significantly reduced risk of OSCC and GCA. Cysteine should be further investigated for its potential as a chemopreventive agent for upper gastrointestinal cancers.

Background

Cancers of the upper gastrointestinal tract remain a substantial cause of morbidity and mortality worldwide. Ghrelin is a hormone produced in the oxyntic glands of the stomach, and under conditions of chronic inflammation and atrophy, serum ghrelin concentrations decrease. However, the relationship between ghrelin and the risk of gastric and esophagogastric junctional cancers has not been investigated.

Methods

We conducted a nested case–control study within the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine the relationship between serum ghrelin concentration and the risk of gastric noncardia adenocarcinoma (GNCA) and esophagogastric junctional adenocarcinoma (EGJA). Data from 261 GNCA patients, 98 EGJA patients, and 441 control subjects were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for potential confounders. Lag analysis was also performed to investigate the temporal nature of the associations between baseline serum pepsinogen I and ghrelin in GNCA and EGJA patients. All statistical tests were two-sided.

Results

Lower concentrations of serum ghrelin were statistically significantly associated with an increased risk of both GNCA (adjusted OR = 1.75, 95% CI = 1.49 to 2.04; P < .001) and EGJA (adjusted OR = 1.56, 95% CI = 1.28 to 1.89, P < .001). A multivariable model found that the risk of both GNCA and EGJA were statistically significantly increased for those individuals in the lowest quartile of serum ghrelin levels compared with those in the highest quartile (OR of GNCA = 5.63, 95% CI = 3.16 to 10.03; OR of EGJA = 4.90, 95% CI = 2.11 to 11.35). The statistical significance of these associations remained even after restricting the analysis to those patients who developed cancer more than 10 years after baseline serum ghrelin measurements.

Conclusion

Low baseline concentrations of serum ghrelin were associated with a statistically significant increase in the risk of GNCA and EGJA, suggesting a potential role for gastric hormones in carcinogenesis.

BACKGROUND

The national and international epidemic of chronic disease, including among children, is largely fueled by increasing obesity. It is recommended that primary care play a key role in the treatment of pediatric obesity.

METHODS

A written survey was administered to providers and staff at 13 primary care practices across North Carolina, assessing perceptions on multiple dimensions of pediatric obesity treatment and knowledge of dietitian services.

RESULTS

The response rate for the survey was 66.9% (n = 273). Although providers reported feeling comfortable and confident in many areas of childhood obesity, perceived effectiveness was low. Moreover, comfort and confidence were lower for non–primary care providers (PCPs) involved in obesity treatment than for PCPs, and PCP comfort and confidence levels were low for the ability to conduct motivational interviewing and for knowledge of billing for obesity as a diagnosis. Personnel perceived that there were benefits to having a registered dietitian (RD) in their practice and generally understood RD capacity. Survey results provided no evidence that integration of an RD into the practice changed perceptions or knowledge over the course of 1 year.

LIMITATIONS

The present study included only 13 practices, mostly rural and all of at least moderate size.

CONCLUSION

Significant change is required if primary care practices are to play the role envisioned for them in stemming childhood obesity and chronic disease. Change will require identifying and addressing specific knowledge and skill gaps, such as those identified in this study. Respondents’ positive perceptions of the benefits of RD integration suggest the importance of exploring this clinical model.

Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1β, 6, 8, and 10, alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence.. Overall, SNPs in genes encoding IL-1β, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR = 2.23, 95% CI: 1.07–4.66, P interaction = 0.03) or IL-10 -819 C (OR = 2.18, 95% CI: 1.05–4.51, P interaction = 0.05) had an elevated risk of high risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 -174 GG in combination with above median flavonol intake (OR = 0.14, 95% CI: 0.03–0.66) or with decreased IL 6 concentrations (OR = 0.14, 95% CI: 0.03–0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence.

Background

Serum adiponectin, leptin, C-peptide, and homocysteine are indicators for obesity, hyperinsulinemia, and chronic inflammation, which have all been associated with colorectal cancer.

Aims

To determine whether serum adiponectin, leptin, C-peptide, and homocysteine are associated with fat, fiber, fruit & vegetable, flavonol, or dry bean intake, and colorectal adenoma recurrence.

Methods

Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for adenoma recurrence in 627 participants from the control arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit & vegetable diet on adenoma recurrence.

Results

Serum concentrations of C-peptide and homocysteine were inversely related to fiber, fruits & vegetables, and flavonol intake and positively related to percentage of calories from fat (all Ptrend ≤ 0.01). High homocysteine concentrations were associated with any (4th versus 1st quartile, OR = 2.26, 95% CI: 1.30-3.94) and more than one adenoma recurrence (OR = 2.11, 95% CI: 1.01-4.40). Individuals in the highest, versus lowest, tertile of serum leptin concentration had a decreased risk of advanced adenoma recurrence (OR = 0.22, 95% CI: 0.06-0.79).

Conclusion

Our results suggest that serum homocysteine may serve as an indicator of dietary exposure, including a low-fat and high-fiber, -fruit & vegetable, and -flavonol diet, as well as colorectal adenoma recurrence.

Impact

Discovering biomarkers that are both modifiable and can predict cancer risk is critical. We identified serum homocysteine as a novel indicator that is modified by diet and predicts risk of adenoma recurrence.

Though incidence of colorectal cancer (CRC) in the US, has declined in recent years, rates remain higher in men than women and the male-to-female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than Whites or Blacks have not been frequently reported. To examine CRC rates by sex across anatomic subsite, age, and racial/ethnic groups, we used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992–2006. Incidence rates were expressed per 100,000 person-years and age-adjusted to the 2000 US Standard Population; MF IRR and 95% confidence intervals were also calculated. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from <1.0 at ages <50 years to 1.4–1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently <1.5; among American Indian/Alaska Natives it was <1.0 across all ages. The MF IRRs for CRC vary markedly according to subsite and age but less by racial/ethnic group. These findings may partially reflect differences in screening experiences and access to medical care but also suggest that etiologic factors may be playing a role.

An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first degree relatives, mostly in Western populations. Limited data exists from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women.

We followed 73,358 women in the Shanghai Women’s Health Study for cancer incidence until December 2005. After an average of 7 years of follow-up, 391 women were diagnosed with colorectal cancer. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards models adjusted for age, smoking, family income, education, body mass index, physical activity and history of diabetes.

We observed a significant association between colorectal cancer risk and history of a parent being diagnosed with colorectal cancer (hazard ratio: 3.34; 95% confidence interval: 1.58, 7.06). No association was observed for colorectal cancer diagnosed among siblings. Colorectal cancer risk was not influenced by a positive family history of cancer generally or any of the other cancers investigated (lung, breast, prostate, gastric, esophageal, endometrial, ovarian, urinary tract, central nervous system, small bowel).

Our cohort results suggest that, consistent with findings from Western populations, having a family history of colorectal cancer may influence colorectal cancer risk to a similar extent in a low-risk population.

Background

Beginning a graduate medical education training program is associated with a steep learning curve for incoming residents.

Objective

To compare the efficacy and efficiency of live versus webcast formats for Institutional Orientation.

Methods

This 2-year non-blinded study, with a nonrandomized cohort, compares outcomes for trainees oriented Summer 2005 in a ‘‘live-lecture’’ format with trainees oriented Summer 2006 using a webcast format. Outcomes include posttest success, the time required, presentation quality and utility, and cost.

Results

In 2005, 249 trainees attended the live orientation. Of the 211 who completed the posttest; 132 (63%) passed it within 3 attempts. Of the 241 trainees in 2006, 236 completed the posttest. Of these, 215 (91%) passed it within 3 attempts. Compared to the live-lecture cohort, the webcast cohort rated the posttest as more difficult. Despite performing better, significantly fewer trainees in the webcast cohort rated the posttest as “appropriate” (χ2 =  5 28.57, df 5 1, P , .001). There were no significant differences between the 2 groups on their perceptions of quality and utility of the presentations. While the first year cost of the webcast exceeded that of live lectures, the amortized cost was nearly identical to the live-lecture costs.

Discussion

As corroborated by resident comments, the web-based approach was more effective because it provided trainees flexibility regarding when to study, options on how to view the material, and opportunities to review it if needed for mastery. We plan to continue using the webcast strategy, revising the content as needed.