Lifestyle factors associated with survival after colorectal cancer diagnosis

Background:

Aside from tumour stage and treatment, little is known about potential factors that may influence survival in colorectal cancer patients. The aim of this study was to investigate the associations between physical activity, obesity and smoking and disease-specific and overall mortality after a colorectal cancer diagnosis.

Methods:

A cohort of 879 colorectal cancer patients, diagnosed in Western Australia between 2005 and 2007, were followed up to 30 June 2012. Cox''s regression models were used to estimate the hazard ratios (HR) for colorectal cancer-specific and overall mortality associated with self-reported pre-diagnosis physical activity, body mass index (BMI) and smoking.

Results:

Significantly lower overall and colorectal cancer-specific mortality was seen in females who reported any level of recent physical activity than in females reporting no activity. The colorectal cancer-specific mortality HR for increasing levels of physical activity in females were 0.34 (95% CI=0.15, 0.75), 0.37 (95% CI=0.17, 0.81) and 0.41 (95% CI=0.18, 0.90). Overweight and obese women had almost twice the risk of dying from any cause or colorectal cancer compared with women of normal weight. Females who were current smokers had worse overall and colorectal cancer-specific mortality than never smokers (overall HR=2.64, 95% CI=1.18, 5.93; colorectal cancer-specific HR=2.70, 95% CI=1.16, 6.29). No significant associations were found in males.

Conclusion:

Physical activity, BMI and smoking may influence survival after a diagnosis of colorectal cancer, with more pronounced results found for females than for males.     

Diabetes and prognosis in older persons with colorectal cancer

Background:

Epidemiological studies have reported that diabetes significantly increases overall mortality in patients with colorectal cancer. However, it is unclear whether diabetes increases colorectal cancer-specific mortality. We used the US Surveillance Epidemiology and End Results (SEER) database linked with Medicare claims data to assess the influence of pre-existing diabetes on prognosis of patients with colorectal cancer.

Methods:

Data from 61 213 patients aged 67 or older with colorectal cancer diagnosed between 2003 and 2009 were extracted and prospectively followed through the date of death or the end of 2012 if the patient was still alive. Diabetes cases with and without complications were identified based on an algorithm developed for the Chronic Condition Data Warehouse (CCW). Cox models were used to estimate hazard ratios (HRs) for total mortality. The proportional subdistribution hazards model proposed by Fine and Gray was used to estimate HRs for colorectal cancer-specific mortality.

Results:

Compared with patients without diabetes, colorectal cancer patients with pre-existing diabetes had significantly higher risk of overall mortality (HR=1.20, 95 % confidence interval (95% CI): 1.17–1.23). The HR for overall mortality was more pronounced for patients who had diabetes with complications (HR=1.50, 95% CI: 1.42–1.58). However, diabetes was not associated with increased colorectal cancer-specific mortality after accounting for non-colorectal cancer outcomes as competing risk.

Conclusions:

Pre-existing diabetes increased risk of total mortality among patients with colorectal cancer, especially among cancer patients who had diabetes with complications. The increased risk of total mortality associated with diabetes was primarily explained by increased cardiovascular-specific mortality, not by increased colorectal cancer-specific mortality.     

Relationship between aspirin use after diagnosis of colorectal cancer and patient survival: a meta-analysis of observational studies

Background:

Epidemiological evidence suggests that use of aspirin after the diagnosis of colorectal cancer can lengthen survival. However, the supporting data vary between studies, and this hypothesis remains controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between use of aspirin after diagnosis of colorectal cancer and patient survival.

Methods:

We searched the Medline and Embase databases up to April 2014 to identify studies related to aspirin use after diagnosis and all-cause mortality or colorectal cancer-specific mortality. Summary effect estimates with 95% confidence intervals (CIs) were derived using a fixed or random effects model, depending on the heterogeneity between the included studies.

Results:

Seven epidemiologic studies that consisted of six cohort studies and one nested case–control study were included in this meta-analysis. The hazard ratio (HR) of the association between aspirin use after colorectal cancer diagnosis and overall mortality, which was reported in five studies, was 0.74 (95% CI, 0.62–0.89) using a random model (heterogeneity test P=0.003, I²=75.3%), and for colorectal cancer-specific mortality (four studies), it was 0.75 (95% CI, 0.51–1.10) using a random model (heterogeneity test P=0.001, I²=84.1%). In addition, we analysed postdiagnosis aspirin use according to whether aspirin was also used before diagnosis. The HR for the overall mortality of patients who did not use aspirin before diagnosis, which was reported in four studies, was 0.84 (95% CI, 0.70–1.00), and for colorectal cancer-specific mortality (three studies), it was 0.79 (95% CI, 0.61–1.02). For those who did use aspirin before diagnosis, the HR for overall mortality (four studies) was 0.88 (95% CI, 0.83–0.93), and for colorectal cancer-specific mortality (three studies), it was 0.80 (95% CI, 0.59–1.09). Subgroup analysis showed that use of aspirin after diagnosis was associated with longer overall survival among patients with the variant PIK3CA gene but not for those with wild-type PIK3CA.

Conclusions:

Based on current evidence, the use of aspirin after diagnosis does not reduce colorectal cancer-specific mortality, but it does reduce all-cause mortality for colorectal cancer patients.     

Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer

Background:

In an earlier study, a 25-hydroxyvitamin D₃ (25(OH)D) score calculated from known predictors of vitamin D status significantly predicted plasma levels of 25(OH)D and the risk of colorectal cancer, but the influence of the 25(OH)D score on survival after diagnosis is unknown.

Materials and methods:

We prospectively examined the influence of post-diagnosis predicted 25(OH)D levels on mortality among 1017 participants in the Nurses'' Health Study and Health Professionals Follow-Up Study who were diagnosed with colorectal cancer from 1986 to 2004. Colorectal cancer-specific and overall mortality according to quintiles of predicted 25(OH)D levels were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) adjusted for other risk factors of survival.

Results:

Higher predicted 25(OH)D levels were associated with a significant reduction in colorectal cancer-specific (P trend=0.02) and overall mortality (P trend=0.002). Compared with levels in the lowest quintile, participants with predicted 25(OH)D levels in the highest quintile had an adjusted HR of 0.50 (95% CI, 0.26–0.95) for cancer-specific mortality and 0.62 (95% CI, 0.42–0.93) for overall mortality.

Conclusion:

Higher predicted 25(OH)D levels after a diagnosis of colorectal cancer may be associated with improved survival. Further study of the vitamin D pathway in colorectal cancer is warranted.     

Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality

Background:

Aims of this study were to describe the prevalence of comorbidity in newly diagnosed elderly cancer cases compared with the background population and to describe its influence on overall and cancer mortality.

Methods:

Population-based study of all 70+ year-olds in a Danish province diagnosed with breast, lung, colorectal, prostate, or ovarian cancer from 1 January 1996 to 31 December 2006. Comorbidity was measured according to Charlson''s comorbidity index (CCI). Prevalence of comorbidity in newly diagnosed cancer patients was compared with a control group by conditional logistic regression, and influence of comorbidity on mortality was analysed by Cox proportional hazards method.

Results:

A total of 6325 incident cancer cases were identified. Elderly lung and colorectal cancer patients had significantly more comorbidity than the background population. Severe comorbidity was associated with higher overall mortality in the lung, colorectal, and prostate cancer patients, hazard ratios 1.51 (95% CI 1.24–1.83), 1.41 (95% CI 1.14–1.73), and 2.14 (95% CI 1.65–2.77), respectively. Comorbidity did not affect cancer-specific mortality in general.

Conclusion:

Colorectal and lung cancer was associated with increased comorbidity burden in the elderly compared with the background population. Comorbidity was associated with increased overall mortality in elderly cancer patients but not consistently with cancer-specific mortality.     

Influence of comorbidity on the effect of adjuvant treatment and age in patients with early-stage breast cancer

Background:

Prevalence of comorbidity at breast cancer diagnosis increases with age and is likely to influence the likelihood of receiving treatment according to guidelines. The aim of this study was to examine the effect of breast cancer treatment on mortality, taking age at diagnosis and comorbidity into account.

Methods:

Four nationwide population registries in Denmark: the Danish Civil Registration System, the Danish Breast Cancer Cooperative Group, the Danish National Patient Register, and the Danish Register of Causes of Death provided information on 62 591 women diagnosed with early-stage breast cancer, 1990–2008, of whom data on treatment were available for 39 943. Comorbidity was measured using the Charlson Comorbidity Index. Adjuvant treatment were categorised as none, chemotherapy, endocrine therapy, and unknown. Multivariable Cox modelling assessed the effect of comorbidity on breast cancer-specific mortality and other cause mortality according to treatment, adjusting for age at diagnosis and other clinical prognostic factors.

Results:

The impact of comorbidity on mortality was most pronounced in patients aged 50–79 years. Patients receiving chemotherapy with mild to moderate comorbidity had HR 0.99 (95% confidence interval (CI); 0.82–1.19) and 1.06 (95% CI; 0.77–1.46) for breast cancer-specific mortality, respectively, compared with patients without comorbidity.

Conclusion:

Comorbidity at breast cancer diagnosis is an independent adverse prognostic factor for death after breast cancer. We identified a subgroup of patients with mild to moderate comorbidity receiving chemotherapy who had similar breast cancer mortality as patients with no comorbidity.     

Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women

Background:

Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone therapy (HT) independently decrease the risk of colorectal cancer. However, their role in altering survival after a colorectal cancer diagnosis is not well established.

Methods:

We examined the association between the use of these common medications before diagnosis and colorectal cancer survival among women in western Washington State diagnosed with incident colorectal cancer from 1997 to 2002. Cases were ascertained using the Surveillance, Epidemiology and End Results cancer registry; mortality follow-up was completed through linkages to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We observed no overall association between colorectal cancer survival and pre-diagnostic NSAID use. However, when stratified by tumour sub-site, NSAID use was associated with a reduced risk of colorectal cancer mortality for women diagnosed with proximal (HR=0.55; 95% CI: 0.32–0.92), but not distal or rectal (HR=1.32; 95% CI: 0.83–2.10) tumours. The usage of HT was not associated with colorectal cancer survival overall or by tumour sub-site.

Conclusion:

Usage of NSAIDs before diagnosis may be associated with improved colorectal cancer survival among women diagnosed with proximal tumours. The usage of HT does not appear to have a function in altering colorectal cancer mortality.     

Serum lactate dehydrogenase and survival following cancer diagnosis

Background:

There is evidence that high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in several malignancies, but its link to cancer-specific survival is unclear.

Methods:

A total of 7895 individuals diagnosed with cancer between 1986 and 1999 were selected for this study. Multivariable Cox proportional hazards regression was used to assess overall and cancer-specific death by the z-score and clinical categories of serum LDH prospectively collected within 3 years before diagnosis. Site-specific analysis was performed for major cancers. Analysis was repeated by different lag times between LDH measurements and diagnosis.

Results:

At the end of follow-up, 5799 participants were deceased. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific death in the multivariable model were 1.43 (1.31–1.56) and 1.46 (1.32–1.61), respectively, for high compared with low prediagnostic LDH. Site-specific analysis showed high LDH to correlate with an increased risk of death from prostate, pulmonary, colorectal, gastro-oesophageal, gynaecological and haematological cancers. Serum LDH assessed within intervals closer to diagnosis was more strongly associated with overall and cancer-specific death.

Conclusions:

Our findings demonstrated an inverse association of baseline serum LDH with cancer-specific survival, corroborating its role in cancer progression.     

Pre-existing diabetes and breast cancer prognosis among elderly women

Background:

The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis.

Methods:

Women (n=2833) with centrally confirmed invasive breast cancer in the Women''s Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality.

Results:

Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23–2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86–2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality.

Conclusions:

Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality.     

A clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes B colorectal cancer

Background:

The prognosis of patients with Dukes stage B colorectal cancer is unpredictable and there is continuing interest in simply and reliably identifying patients at high risk of developing recurrence and dying of their disease. The aim of this study was to devise a clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes stage B colorectal cancer.

Methods:

A total of 1350 patients who underwent surgery for Dukes stage B colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the analysis.

Results:

On follow-up, 926 patients died of whom 479 died of their cancer. At 10 years, cancer-specific survival was 61% and overall survival was 38%. On multivariate analysis, age ⩾75 (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.15–1.82, P=0.001), emergency presentation (HR 1.59, 95% CI 1.27–1.99, P<0.001) and anastomotic leak (HR 2.17, 95% CI 1.24–3.78, P<0.01) were independently associated with cancer-specific survival in colon cancer. On multivariate analysis, only age ⩾75 (HR 1.58, 95% CI 1.14–2.18, P<0.01) was associated with cancer-specific survival in rectal cancer. Age, presentation and anastomotic leak hazards could be simply added to form a clinical risk score from 0 to 2 in colon cancer. In patients with Dukes B stage colon cancer, the cancer-specific survival at 5 years for patients with a cumulative score 0 was 81%, 1 was 67% and 2 was 63%. The cancer-specific survival rate at 10 years for patients with a clinical risk score of 0 was 72%, 1 was 58% and 2 was 53%.

Conclusion:

The results of this study, in a mature cohort, introduce a new simple clinical risk score for patients undergoing surgery for Dukes B colon cancer. This provides a solid foundation for the examination of the impact of additional factors and treatment on prediction of 3-, 5- and 10-year cancer-specific survival.     

Efficacy and toxicity of external-beam radiation therapy for localised prostate cancer: a network meta-analysis

Background:

Many radiation regimens for treating prostate cancer have been used over the years, but which regimen is optimal for localised or locally advanced prostate cancer lacks consensus. We performed a network meta-analysis to identify the optimal radiation regimen.

Methods:

We systematically reviewed data from 27 randomised controlled trials and could group seven radiation regimens as follows: low- and high-dose radiation therapy (LDRT and HDRT), LDRT+ short- or long-term androgen deprivation therapy (LDRT+SADT and LDRT+LADT), HDRT+SADT, hypofractionated radiotherapy (HFRT), and HFRT+SADT. The main outcomes were overall mortality (OM), prostate-specific antigen (PSA) failure, cancer-specific mortality, and adverse events.

Results:

For the network meta-analysis of 27 trials, LDRT+LADT and LDRT+SADT were associated with decreased risk of OM as compared with LDRT alone as was LDRT+LADT compared with HDRT. Apart from HFRT, all other treatments were associated with decreased risk of PSA failure as compared with LDRT. HFRT+SADT was associated with decreased risk of cancer-specific mortality as compared with HFRT, LDRT+SADT, HDRT, and LDRT.

Conclusions:

HFRT+SADT therapy might be the most efficacious treatment but with worst toxicity for localised or locally advanced prostate cancer, and HDRT showed excellent efficacy but more adverse events.     

Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study

Background:

Aspirin has been widely reported to reduce the incidence of colorectal cancer. Recently, a survival benefit after diagnosis has also been suggested. Data regarding such a benefit are to date contradictory. This study examines the effect of non-steroidal anti-inflammatory drug (NSAID) use on mortality in colorectal cancer in a larger patient cohort than previously to further clarify this effect, especially in terms of exposure timing and dosing.

Methods:

A study using the General Practice Research Database assessed whether aspirin or NSAID exposure in the year immediately following diagnosis affected all-cause mortality in a cohort of 13 994 colorectal cancer patients. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index and comorbidity.

Results:

Overall mortality was slightly lower in patients treated with aspirin, (hazard ratio (HR)=0.91; 95% confidence interval (CI)=0.82–1.00). This effect was observed only in patients treated with prophylaxis-dose aspirin (HR=0.89, CI=0.80–0.98) and only in patients taking aspirin before diagnosis (HR=0.86, CI=0.76–0.98). Differential effects were observed depending on the time after diagnosis. Up to 5 years, a reduction in mortality was observed for aspirin users (HR=0.83, CI=0.75–0.92), whereas after 10 years there was an increase in mortality (HR=1.94, CI=1.26–2.99). For NSAID use, no significant effect was observed on overall mortality (HR=1.07, CI=0.98–1.15). High-dose NSAID use was associated with a slight increase in mortality (HR=1.41, CI=1.26–1.56).

Interpretation:

These findings provide further indication that aspirin may be beneficial in reducing mortality in colorectal cancer during the first 5 years. The same cannot be said for other NSAIDs, where a small increase in mortality was observed.     

Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer

Background:

AMP-activated protein kinase (AMPK, PRKA) has central roles in cellular metabolic sensing and energy balance homeostasis, and interacts with various pathways (e.g., TP53 (p53), FASN, MTOR and MAPK3/1 (ERK)). AMP-activated protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a tumour suppressor and a potential therapeutic target. However, no study has examined its prognostic role in colorectal cancers.

Methods:

Among 718 colon and rectal cancers, phosphorylated AMPK (p-AMPK) and p-MAPK3/1 expression was detected in 409 and 202 tumours, respectively, by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations.

Results:

Phosphorylated AMPK expression was not associated with survival among all patients. Notably, prognostic effect of p-AMPK significantly differed by p-MAPK3/1 status (P_interaction=0.0017). Phosphorylated AMPK expression was associated with superior colorectal cancer-specific survival (adjusted HR 0.42; 95% confidence interval (CI), 0.24–0.74) among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases (adjusted HR 1.22; 95% CI: 0.85–1.75).

Conclusion:

Phosphorylated AMPK expression in colorectal cancer is associated with superior prognosis among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases, suggesting a possible interaction between the AMPK and MAPK pathways influencing tumour behaviour.     

Emergency presentation of cancer and short-term mortality

Background:

The short-term survival following a cancer diagnosis in England is lower than that in comparable countries, with the difference in excess mortality primarily occurring in the months immediately after diagnosis. We assess the impact of emergency presentation (EP) on the excess mortality in England over the course of the year following diagnosis.

Methods:

All colorectal and cervical cancers presenting in England and all breast, lung, and prostate cancers in the East of England in 2006–2008 are included. The variation in the likelihood of EP with age, stage, sex, co-morbidity, and income deprivation is modelled. The excess mortality over 0–1, 1–3, 3–6, and 6–12 months after diagnosis and its dependence on these case-mix factors and presentation route is then examined.

Results:

More advanced stage and older age are predictive of EP, as to a lesser extent are co-morbidity, higher income deprivation, and female sex. In the first month after diagnosis, we observe case-mix-adjusted excess mortality rate ratios of 7.5 (cervical), 5.9 (colorectal), 11.7 (breast ), 4.0 (lung), and 20.8 (prostate) for EP compared with non-EP.

Conclusion:

Individuals who present as an emergency experience high short-term mortality in all cancer types examined compared with non-EPs. This is partly a case-mix effect but EP remains predictive of short-term mortality even when age, stage, and co-morbidity are accounted for.     

Breast cancer incidence and mortality in a transitioning Chinese population: current and future trends

Background:

Projections of future trends in cancer incidence and mortality are important for public health planning.

Methods:

By using 1976–2010 data in Hong Kong, we fitted Poisson age-period-cohort models and made projections for future breast cancer incidence and mortality to 2025.

Results:

Age-standardised breast cancer incidence (/mortality) is projected to increase (/decline) from 56.7 (/9.3) in 2011–2015 to 62.5 (/8.6) per 100 000 women in 2021–2025.

Conclusions:

The incidence pattern may relate to Hong Kong''s socio-economic developmental history, while falling mortality trends are, most likely, due to improvements in survival from treatment advancement and improved health service delivery.     

Vitamin C intake and breast cancer mortality in a cohort of Swedish women

Background:

Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied.

Methods:

Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort.

Results:

From 1987–2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57–0.99) compared with those in the lowest quartile (P_trend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR=0.84; 95% CI=0.71–1.00; P_trend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (≈1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52–2.17).

Conclusion:

Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.     

Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.

Methods:

We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.

Results:

After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.

Conclusion:

Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.     

Non-steroidal anti-inflammatory drug and aspirin use and the risk of head and neck cancer

Background:

Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect.

Methods:

Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC.

Results:

Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use.

Conclusion:

Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.     

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM

Background:

Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests.

Methods:

We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up.

Results:

Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81–4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations.

Conclusions:

Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.