Smoking compromises cause-specific survival in patients with operable colorectal cancer

AimsTo assess whether active smoking compromises survival in patients with colorectal cancer.Materials and methodsWe studied a regionally based cohort of 284 consecutive patients referred to the Tayside Cancer Centre for consideration of adjuvant treatment after curative surgery for colorectal cancer.ResultsCause-specific survival was significantly worse (P = 0.0015) in patients who were actively smoking at the time of their first post-operative visit. The absolute difference in 5-year cause-specific survival (active smokers vs the rest) was 21%. In adjusted multi-variate analysis of patients after pathologically complete (R0) resection, the hazard ratio was 2.55 (95% confidence interval 1.40–4.64) in active smokers compared with non-smokers. T stage, number of positive nodes and co-morbidity score were also of independent prognostic influence.ConclusionsPersistent smoking was, in this small series, an important and independent predictor of cancer-related death after surgery for cancer of the large bowel. Because smoking and deprivation are related, some of the adverse effects of deprivation upon survival in this group of patients may be explained by smoking behaviour.     

Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus

BackgroundWhether metformin therapy affects incident prostate cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated.MethodsThe National Health Insurance reimbursement database of Taiwanese male patients with new-onset T2DM between 1998 and 2002 and aged ⩾40 years (n = 395,481) were retrieved to follow up prostate cancer incidence until the end of 2009. Metformin was treated as a time-dependent variable. Of the patients studied, 209,269 were never-users and 186,212 were ever-users. A time-dependent approach was used to calculate prostate cancer incidence and estimate hazard ratios using Cox regression for ever-users, never-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). Sensitivity analyses were conducted in various subgroups, using time-dependent and non-time-dependent approaches.ResultsDuring the follow-up, 2776 metformin ever-users and 9642 never-users developed prostate cancer, representing an incidence of 239.42 and 737.10 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) after adjustment for propensity score (PS) for ever- versus never-users was 0.467 (0.446–0.488). The PS-adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 0.741 (0.698–0.786), 0.474 (0.441–0.508) and 0.231 (0.212–0.253), respectively (P-trend < 0.001); and were 0.742 (0.700–0.786), 0.436 (0.406–0.468) and 0.228 (0.208–0.251) for the respective cumulative dose (P-trend < 0.001). Sensitivity analyses consistently supported a protective effect of metformin on incident prostate cancer.ConclusionsMetformin use is associated with a decreased risk of incident prostate cancer in Taiwanese male patients with T2DM.     

Oesophageal cancer in The Netherlands: increasing incidence and mortality but improving survival

AimOesophageal cancer is highly lethal with a 5-year relative survival of 10–15%. An increasing incidence has been reported for several parts of the Western world. We studied time trends in incidence, mortality and survival for oesophageal cancer in the Netherlands during 1989–2003.MethodsData on incidence and survival were obtained from the Netherlands Cancer Registry and mortality data from Statistics Netherlands.ResultsThe age standardised incidence increased by 3.4% (p < 0.001) and 1.9% (p = 0.003) per year for males and females, respectively. This increase was almost exclusively caused by oesophageal adenocarcinomas. Age standardised mortality increased 2.5% (p < 0.001) per year among males and 1.7% (p = 0.002) per year among females. Relative survival improved significantly from 8.1% in 1989–1993 to 12.6% in 1999–2003 (p < 0.001). Adjusted for age, stage, tumour location and surgery, the excess risk of death decreased by 22%.ConclusionOesophageal carcinoma incidence is rising in the Netherlands. Mortality increased at a slightly lower pace due to improving survival.     

Predictors of the use of complementary and alternative medicine (CAM) by women at high risk for breast cancer

BackgroundFew data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer.MethodsSelf-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression.ResultsOf 892 women, 55% (n = 489) used CAM, 6% (n = 53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83–3.58, p < 0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00–1.10, p = 0.049), greater anxiety (OR 1.92, 95% CI 1.16–3.16, p = 0.01), not currently smoking (OR 0.64, 95% CI 0.42–0.97, p = 0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72–0.94, p = 0.005).ConclusionsThe majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer.     

Cardiorespiratory fitness,lifestyle factors and cancer risk and mortality in Finnish men

BackgroundPhysical fitness along with lifestyle factors may have important roles in the prevention of cancer. We examined the relationship between common lifestyle factors such as energy expenditure, physical activity and maximal oxygen uptake (VO_2max), nutrition and smoking habits and the risk of cancer.MethodsA population-based cohort study was carried out in 2268 men from Eastern Finland with no history of cancer. They were followed up for an average of 16.7 years. The outcome measures were cancer incidence (n = 387) and cancer mortality (n = 159).ResultsMen with VO_2max of more than 33.2 mL/kg/min (highest tertile) had 27% (95% confidence interval (CI) 0.56–0.97) decreased cancer incidence and 37% (95% CI 0.40–0.97) reduced cancer mortality than men with VO_2max of less than 26.9 mL/kg/min (lowest tertile) after adjustment for age, examination year, alcohol, smoking, socioeconomic status, waist-to-hip ratio and energy, fibre and fat intake. The risk reduction was mainly due to decreased risk of lung cancer in fit men. The adjusted risk of cancer was 0.73 (95% CI 0.55–0.98) among fit (VO_2max ? 26.9 mL/kg/min) men with the total energy expenditure of physical activity over 2500 kcal/week. A total of 290 active (energy expenditure >2500 kcal and at least 2 h of physical activity per week) men with a favourable lifestyle (good fitness, balanced diet and non-smoking) had an adjusted relative risk of 0.63 (95% CI 0.46–0.87) for cancer.ConclusionFavourable lifestyle including good cardiorespiratory fitness and healthy dietary habits with active and non-smoking lifestyle considerably reduces the risk of cancer.     

Effect of cigarette smoking on quality of life in small cell lung cancer patients

BackgroundContinued cigarette smoking after small cell lung cancer (SCLC) diagnosis has been shown to shorten patients’ survival, but little is known about the impact of smoking and cessation on quality of life (QOL) profile (e.g., overall QOL, pain, fatigue, cough, dyspnea, appetite change, and performance status) in SCLC survivors (who survived at least 6 months post initial diagnosis). In this study, we sought to evaluate the relationship between cigarette smoking and QOL profiles in SCLC patients.MethodsA total of 223 survivors were classified into five groups: never smokers, former smokers (quit more than 1 year prior to diagnosis), recent quitters (quit within 1 year surrounding diagnosis), late quitters (quit after 1 year post diagnosis) and never quitters. One hundred and sixty-eight of these survivors were matched with 334 lung-cancer-free controls on age, gender, and smoking status for comparative analysis. QOL scales were scored from 0 (worse) to 100 (best). Conditional logistic regression, linear mixed-effect models, and Wilcoxon signed rank tests were used.ResultsSCLC survivors consistently showed a significant deficit in QOL profile; e.g., mean overall QOL in patients was 17.5 points worse than the controls (p < 0.0001). Among all smokers, former smokers reported the best QOL profile, while late or never quitters reported the worst. The recent quitters showed an improving trend in QOL profile and lower percent of reduced appetite (an average of 43%) compared to the late or never quitters (58%).ConclusionsOur study confirmed the negative impact of smoking on SCLC survivors’ QOL and found that smoking cessation surrounding the time of diagnosis could improve overall QOL and symptoms. The findings of this study provide evidence for oncologists to recommend smoking cessation to their SCLC patients.     

Active and passive cigarette smoking and the risk of endometrial cancer in Poland

BackgroundEpidemiological studies have consistently reported that active cigarette smoking is inversely associated with endometrial cancer risk. However, dose-response relationships with quantitative measures of active smoking or passive smoking remain less clear.MethodsData on lifetime active and passive smoking were collected for 551 endometrial cancer cases and 1925 controls in a population-based case-control study conducted during 2001–2003 in Poland (Warsaw and ?ódz).ResultsCompared with never active smokers, active current (Odds Ratio (OR) = 0.51, 95% Confidence Interval (CI): 0.39, 0.68) and former smokers (OR = 0.60, 95% CI: 0.45, 0.80) were at a statistically significantly decreased risk. We did not observe statistically significant inverse dose-response relationships with increasing exposure with duration and cumulative measures. However, there was some indication that the highest category of number of years (OR = 0.35, 95% CI: 0.23–0.55), intensity (OR = 0.41, 95% CI: 0.24–0.69), and dose (OR = 0.38, 95% CI: 0.24–0.60) of smoking among current smokers had the greatest inverse association compared to never smokers. Our data did not support the presence of an inverse association with passive smoking among never active smokers (OR = 0.92; 95% CI: 0.65, 1.29).ConclusionOur results support that long-term and heavy smoking among current smokers strongly influence endometrial cancer risk.     

The risk of skin rash and stomatitis with the mammalian target of rapamycin inhibitor temsirolimus: a systematic review of the literature and meta-analysis

ObjectiveWe conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing skin rash and stomatitis among patients receiving temsirolimus.MethodsDatabases from PubMed and Web of Science from January, 1998 until June, 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of skin rash and stomatitis were calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies.ResultsA total of 779 patients from 10 clinical trials were included in this analysis. The overall incidence of all-grade rash was 45.8% (95% confidence interval (CI): 35.6–56.3%), with a RR of 7.6 (95% CI: 4.4–13.3; p < 0.001). The overall incidence of high-grade rash was 3.3% (95% CI: 1.9–5.6%), with a RR of 13.70 (95% CI: 0.82–227.50, p = 0.07). The overall incidence of all-grade stomatitis was 44.3% (CI: 32.1–57.1%), with a RR of 11.10, 95% CI: 5.60–22.00; p < 0.001). The overall incidence of high-grade stomatitis was 3.2% (95% CI: 1.9–5.4%), with a RR of 13.2 (95% CI: 0.80–218.50, p = 0.07).ConclusionThere is a significant risk of developing skin rash and stomatitis in cancer patients receiving temsirolimus. The risk is independent of underlying tumour. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing.     

Cigarette smoking and pancreatic cancer risk: More to the story than just pack-years

PurposeCigarette smoking is an established risk factor for pancreatic adenocarcinoma. However, few studies have thoroughly investigated the effects of independent smoking dimensions (duration, intensity, cumulative dose and time since quitting) on risk estimates. We analysed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, with the aim of determining which smoking component is primarily important to pancreatic cancer risk.MethodsOur study included 705 pancreatic cancer patients and 711 controls. Logistic regression and generalised additive logistic regression (for non-linear dose effects) were used to determine odds ratios (ORs) and 95% confidence intervals (CIs).ResultsCompared to never-smokers, current smokers had an increased risk of pancreatic cancer (OR = 3.4; 95% CI 2.4–5.0) after adjustment for age, sex, education, alcohol intake and birth country. Of the various smoking dimensions, smoking duration and time since quitting had a greater effect on OR estimates (OR 1.3; 95% CI 1.1–1.4 and OR 0.8; 95% CI 0.7–0.8) than smoking intensity (OR 1.1; 95% CI 0.9–1.2), once ever-smoking was accounted for.ConclusionsThis study confirms the association between cigarette smoking and pancreatic adenocarcinoma, and provides evidence to suggest that smoking pattern, in addition to dose effect, may affect disease risk.     

Lead-time in the European Randomised Study of Screening for Prostate Cancer

BackgroundLead-time is defined as the time by which screening advances the diagnosis compared with absence of screening. A sufficiently long lead-time needs to be achieved so that cancer can be detected while still curable. A very short lead-time may indicate poor sensitivity of the screening test, while a very long lead-time suggests overdiagnosis.Material and methodsIn the first screening round, a total of 56,294 men aged 55–74 years were screened with serum prostate specific antigen (PSA) in five countries of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with an overall detection rate (prevalence) of 2.8% (1972 prostate cancers). Prostate cancer incidence among 92,142 men randomly allocated to the control arm of the trial was also assessed. Lead-time was estimated as the time required to accumulate a similar cumulative risk of prostate cancer in the control arm to the detection rate in the intervention arm, i.e. from the ratio of detection rate (prevalence of screen-detected cases) and expected incidence (cumulative risk).ResultsUsing a serum PSA cut-off of 4 ng/ml, the mean lead-time in the whole study population was estimated as 6.8 years (95% confidence interval (95% CI) 7.9–8.4). It was 8 years in The Netherlands, 6 in Sweden and Finland, 5 in Italy and 4 in Belgium. The mean lead-time was similar, 6–7 years, at ages 50–64 years, but close to 8 years among men aged 65–74 years. A lower PSA cut-off level of 3 ng/ml used in Sweden and The Netherlands prolonged the mean lead-time by approximately 1 year. Lead-time based on advanced prostate cancer only was slightly shorter, mean 5.3 years (95% CI 4.6–6.0). The lead-time for the second screening round was slightly shorter than that for the first (5.9, 95% CI 5.4–6.4), reflecting a similar relation between detection rate and control group incidence.ConclusionThe lead-time for prostate cancer found in ERSPC substantially exceeded that found for breast, cervical and colorectal cancer screening. One round of prostate cancer screening can advance clinical diagnosis by 4–8 years. Overdiagnosis or detection of non-progressive tumours may contribute substantially to the lead-time.     

Treatment-related mortality in children with acute myeloid leukaemia in Central America: incidence, timing and predictors

BackgroundCure rates in paediatric acute myeloid leukaemia in low-income countries lag behind those in high-income countries, in part secondary to higher rates of treatment-related mortality. Patterns of treatment-related mortality are likely to differ between low and high-income centres. Understanding low-income setting patterns is necessary before effective interventions aimed at decreasing treatment-related mortality can be designed. Our aim was to describe the incidence, timing and predictors of treatment-related mortality among Central American children with acute myeloid leukaemia.Patients and methodsWe evaluated patients younger than 21 years diagnosed with acute myeloid leukaemia from 2000 to 2008 in El Salvador, Honduras or Guatemala. Biologic, socioeconomic and nutritional variables collected prospectively were examined as potential predictors of treatment-related mortality.ResultsAmong 279 patients, treatment-related mortality occurred in 65 (23%). Of 65 deaths, 51 (78.5%) occurred before or during induction, resulting in an early death rate of 18.3%. The most common causes of treatment-related mortality were infection (29/65; 45%) and haemorrhage (13/65; 20%). Infection accounted for 33% of treatment-related mortality before remission induction therapy versus 40% during induction and 77% after induction (P = 0.03). Rates of treatment-related mortality did not vary between time periods 1 and 2 (24.8% versus 21.4%; P = 0.32). Only lower initial platelet count predicted early death (odds ratio per 10 × 10⁹/L = 0.88, 95% Confidence Interval (CI) 0.79–0.97; P < 0.001).ConclusionsTreatment-related mortality remains a significant cause of treatment failure. Supportive care interventions are needed. Children presenting with low initial platelet counts were at highest risk of induction death, suggesting that transfusion practices should be evaluated.     

ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer specific mortality

BackgroundERG (ETS regulated gene) protein expression has been shown to reflect ERG genomic rearrangements in prostate cancer (PCA). However, ERG protein expression prognostic value has not been yet investigated.DesignERG protein expression was investigated in a cohort of 312 men with PCA diagnosed in transurethral resection of the prostate.ResultsERG expression was detected in 76/293 (25.9%) of patients. Overall ERG expression was associated with Gleason score (GS) (p < 0.0001), tumour volume (p = 0.04) and with cancer specific mortality (p = 0.15). Low ERG intensity was significantly associated with higher GS (p = 0.02) and marginally with cancer specific mortality (p = 0.11). The association with caner specific mortality was more significant in patients without any hormonal manipulation (p = 0.02). Multivariate Cox model using GS, tumour volume and ERG intensity to predict time to cancer specific death yielded a marginally significant effect for high versus low ERG protein expression (hazard ratio (HR) = 0.36; 95% confidence interval (CI): 0.10–1.38; p = 0.14) and a non-significant effect for GS >7 (HR = 4.85; 95% CI: 0.48, 48.65; p = 0.18). Men with ERG expression showed longer free progression time to castration resistant disease compared to men with no ERG expression (mean 11.39 versus 6.1 months, p = 0.08).ConclusionWe report significant association between ERG protein levels and each of GS, progression to castration resistant and cancer specific mortality. High ERG intensity was associated with lower GS, better overall survival and longer free progression times to castration resistant disease. ERG protein levels may have prognostic and therapeutic role in PCA and should be investigated in future studies.     

Patient demographics and lifestyle factors influencing long-term survival of oesophageal cancer and gastric cardia cancer in a nationwide study in Sweden

BackgroundLittle is known about the possible influence of demographic and aetiologic risk factors on the survival amongst patients with oesophageal and cardia cancer.MethodsIn a Swedish nationwide case–control study conducted in 1995–1997, 618 patients diagnosed with oesophageal or cardia cancer were interviewed regarding demographic and lifestyle factors, and followed up for survival through a 2004. Information about the treatment was collected through review of medical records, and 38 patients with missing records were excluded. Survival curves were estimated by Kaplan–Meier method. Cox proportional hazards regression models were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for known or suspected prognostic factors.ResultsAmongst the 580 included patients, 177 had oesophageal adenocarcinoma, 159 oesophageal squamous-cell carcinoma and 244 had cardia adenocarcinoma. Surgical resection was conducted in 224 patients (39%). The overall 5-year survival rate was 12%. Amongst patients with oesophageal adenocarcinoma, obese patients had a favourable prognosis compared to those of normal weight (HR = 0.6, 95%CI 0.3–1.0). Amongst patients with oesophageal squamous-cell carcinoma, lean patients had a better prognosis (HR = 0.6, 95%CI 0.4–1.0), whilst previous smokers (HR = 2.1, 95%CI 1.0–4.4) and low educated (HR = 1.9, 95%CI 1.1–3.4) had a worse prognosis. There were no statistically significant associations between sex, age, reflux symptoms, alcohol consumption or physical activity and prognosis in any of the three studied cancer subtypes.ConclusionsBody mass, tobacco smoking and education might influence the long-term survival of patients with oesophageal cancer.     

Survival of elderly rectal cancer patients not improved: analysis of population based data on the impact of TME surgery

IntroductionThe incidence of rectal cancer is highest in elderly patients. However, these patients are often underrepresented in randomised studies. Therefore, it is not clear whether results of rectal cancer studies are equally applicable to both elderly and younger patients.In this paper, the Dutch Total Mesorectal Excision (TME) study is revisited, focused on patients aged 75 years and above. The rectal cancer databases of the Comprehensive Cancer Centres (CCC) South and West were combined to analyse the effect of the TME-study in three different periods: before (1990–1995), during (1996–1999) and after (2000–2002) the trial.ResultsImplementation of preoperative radiotherapy, as investigated in the TME trial, and the introduction of TME surgery resulted in improved 5 year survival during the subsequent periods, in patients younger than 75 years, of 60% (1990–1995) to 67% (1996–1999) and 70% (2000–2002) (log rank p < 0.0001). The older patients did not improve and remained at 41%, 40% and 43% at 5 years in the respective periods.Furthermore, mortality during the first 6-month period after treatment is significantly raised compared to younger patients: 14% in the elderly, compared to 3.9% in the younger TME-study patient (p < 0.0001 X²). In the CCC database these figures were confirmed at 16% and 3.9% (p < 0.0001 X²).ConclusionOverall survival was not improved in the elderly rectal cancer patient after introduction of preoperative radiotherapy and TME-surgery. Non-cancer related mortality is a significant problem in the first 6 months after surgery.     

Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium

Background and methodsFamilial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals.ResultsIndividuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment.ConclusionsThe occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.     

Cigar and pipe smoking,smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4)

BackgroundCigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco.Materials and methodsWe conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case–control studies (6056 cases and 11 338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates.ResultsCompared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2–2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4–1.6). The OR was 1.1 (95% CI 0.69–1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75–1.3).ConclusionThis collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.     

Increased incidence and survival for oesophageal cancer but not for gastric cardia cancer in the Netherlands

IntroductionA worldwide increasing incidence is seen for oesophageal adenocarcinoma, but not for oesophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma. Purposes of the current study were to evaluate the changing incidence rates of oesophageal and gastric cardia cancer, and to assess survival trends.Patients and methodsPatients diagnosed with oesophageal adenocarcinoma (N = 12,195) or SCC (N = 9046), or gastric cardia adenocarcinoma (N = 9900) between 1989 and 2008 in the Netherlands were included. Changes in European Standard Population (ESP) and relative survival over time were evaluated.ResultsIncidence rates for oesophageal adenocarcinoma increased in males (+7.5%, P < 0.001) and females (+5.2%, P < 0.001), while the incidence for oesophageal SCC remained stable in males (−0.2%, P = 0.6) and slightly increased in females (+1.7%, P = 0.001). The incidence for gastric cardia cancer decreased in males (−1.2%, P < 0.006), and remained stable in females (−0.2%, P = 0.7).Five-year survival for both M0 and M1 oesophageal carcinoma doubled over the last 20 years. No significant changes in survival were found for M0 and M1 gastric cardia carcinoma.DiscussionIn the Netherlands, a rising incidence is seen for oesophageal adenocarcinoma, but not for gastric cardia adenocarcinoma. This finding most likely reflects true changes in disease burden, rather than being the result of changes in diagnosis or classification. The increased survival for oesophageal carcinoma can be attributed to centralisation of surgery, and an increased use of multimodality therapy, factors hardly acknowledged for gastric cancer.     

Non-linear dose–response relationship between cigarette smoking and pancreatic cancer risk: Evidence from a meta-analysis of 42 observational studies

BackgroundQuestion remains about the shape of the dose–response relationship between cigarette smoking and pancreatic cancer risk.MethodsRelevant studies were identified by searching PubMed, ISI Web of Science and China National Knowledge Infrastructure (CNKI) databases and by reviewing the reference lists of retrieved articles. Random-effects models were applied to estimate summary relative risks (RRs).ResultsForty-two publications were finally included. The overall meta-analysis showed evidence of non-linear association between smoking intensity and pancreatic cancer risk (P for non-linearity = 0.000). Compared with non-smokers, the summary RRs were 1.5 (95% confidence interval (CI): 1.4, 1.6) for 10 cigarettes/day, 1.9 (95% CI: 1.8, 2.0) for 20 cigarettes/day, 2.0 (95% CI: 1.9, 2.1) for 30 cigarettes/day and 2.1 (95% CI: 1.9, 2.3) for 40 cigarettes/day with marginal between-study heterogeneity (I² = 29%). Similar results were also found for smoking duration and cumulative amount of cigarettes smoked. Besides, the summary RR for former smokers reduced with increasing time since quitting smoking compared with current smokers without heterogeneity (P for non-linearity = 0.008, I² = 0%). The results of stratified analysis by study design were comparable to those of overall meta-analysis. When stratified by sex, non-linear dose–response associations were detected for all metrics of cigarette smoking in women, while linear relationships were observed for smoking duration and cumulative amount of cigarettes smoked in men except for smoking intensity.ConclusionThis meta-analysis reveals a non-linear dose–response association between cigarette smoking and pancreatic cancer risk, but it might differ between sexes.     

Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation

BackgroundSkin cancers are known to be associated with sun exposure, whereas sunlight through the production of vitamin D may protect against some cancers. The aim of this study was to assess whether patients with skin cancer have an altered risk of developing other cancers.MethodsThe study cohort consisted of 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer extracted from 13 cancer registries. 10,886 melanoma and 35,620 non-melanoma skin cancer cases had second cancers. The observed numbers (O) of 46 types of second primary cancer after skin melanoma, basal cell carcinoma or non-basal cell carcinoma, and of skin cancers following non-skin cancers were compared to the expected numbers (E) derived from the age, sex and calendar period specific cancer incidence rates in each of the cancer registries (O/E = SIR, standardised incidence ratios). Rates from cancer registries classified to sunny countries (Australia, Singapore and Spain) and less sunny countries (Canada, Denmark, Finland, Iceland, Norway, Scotland, Slovenia and Sweden) were compared to each other.ResultsSIR of all second solid primary cancers (except skin and lip) after skin melanoma were significantly lower for the sunny countries (SIR(S) = 1.03; 95% CI 0.99–1.08) than in the less sunny countries (SIR(L) = 1.14; 95%CI 1.11–1.17). The difference was more obvious after non-melanoma skin cancers: after basal cell carcinoma SIR(S)/SIR(L) = 0.65 (95%CI = 0.58–0.72); after non-basal cell carcinoma SIR(S)/SIR(L) = 0.58 (95%CI = 0.50–0.67). In sunny countries, the risk of second primary cancer after non-melanoma skin cancers was lower for most of the cancers except for lip, mouth and non-Hodgkin lymphoma.ConclusionsVitamin D production in the skin seems to decrease the risk of several solid cancers (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma, which is consistent with earlier reports that non-melanoma skin cancers reflect cumulative sun exposure, whereas melanoma is more related to sunburn.     

The lifelong risk of metachronous colorectal cancer justifies long-term colonoscopic follow-up

BackgroundThe aim of this study was to calculate the risk of metachronous colorectal cancers, to specify their characteristics and potential risk factors in a well-defined French population over a 27-year period.Patients and methodsThe 10,801 patients who had colorectal cancers totalled 61,879 person-years of follow-up. The actuarial method was used to obtain crude metachronous colorectal cancer rates. Standardised incidence ratios (SIRs) were calculated.ResultsThe cumulative rate of metachronous colorectal cancer was 1.8% at 5 years, 3.4% at 10 years and 7.2% at 20 years. The incidence of metachronous colorectal cancer following a first colorectal cancer was higher than expected (SIR: 1.5 [1.3–1.7] p < 0.001). It remained greater throughout the study period, significantly only between the first and the fifth years following diagnosis (SIR: 1.9 [1.6–2.3] p < 0.010). As compared to solitary cancers, metachronous cancers were diagnosed at earlier stages (23.5% versus 40.9% were stage I, p < 0.001). None of the personal and tumour characteristics were predicting factors for the development of metachronous colorectal cancer.ConclusionPatients with colorectal cancer are at greater risk of developing a metachronous colorectal cancer. Among them, no predicting factors for the development of metachronous tumours were found. Thus lifelong colonoscopic surveillance is needed.