Statin use and risk of liver cancer: Evidence from two population-based studies

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case–control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43–0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24–0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45–2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.     

Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network

There is increasing interest regarding potential protective effects of low-dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/oesophageal cancer using a population-based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low-dose aspirin (75-300 mg/day) and a matched cohort of nonusers at the start of follow-up from The Health Improvement Network. Cohorts were followed to identify incident cases of gastric/oesophageal cancer. Nested case-control analyses were conducted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs nonuse of low-dose aspirin using logistic regression. Current use was defined as when low-dose aspirin lasted 0 to 90 days before the index date (event date for cases, random date for controls) and previous duration was ≥1 year. We identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. ORs (95% CIs) were 0.46 (0.38-0.57) for gastric cancer and 0.59 (0.51-0.69) for oesophageal cancer. The effect remained consistent with no clear change seen between previous duration of low-dose aspirin use of 1-3, 3-5 or >5 years. The reduced risks was seen with 75 mg/day, and effects were consistent in lag-time analyses. In conclusion, our results indicate that use of low-dose aspirin is associated with a 54% reduced risk of gastric cancer and a 41% reduced risk of oesophageal cancer as supported by mechanistic data.     

Oral disease and risk of oesophageal and gastric cancer in a nationwide nested case-control study in Sweden

The association between the exposure to oral disease and the outcomes of oesophageal and gastric cancer was examined in a Swedish nationwide inpatient register-based nested case-control study in 1964-2008. The study included 6,156 oesophageal squamous-cell carcinoma cases that were compared with 29,993 controls, 2684 oesophageal adenocarcinoma cases that were compared with 15,036 controls and 38,308 gastric cancer cases that were compared with 99,991 controls. For oesophageal squamous cell carcinoma, the age and sex adjusted odds ratio (OR) among patients with a history of oral disease was 1.3 (95% confidence interval (95% CI): 0.9,−1.9), and 1.1 (95% CI 0.8,−1.7) after adjustment for diseases related to alcohol consumption or tobacco smoking. For oesophageal adenocarcinoma, the age and sex adjusted OR was increased (OR 1.7, 95% CI 1.1-2.6), and remained increased (OR 1.6, 95% CI 1.0-2.4) after adjustment for diseases related to smoking or alcohol consumption, gastroesophageal reflux, obesity and ulcer disease. For gastric cancer, no statistically significantly increased risk was observed (age and sex adjusted OR 0.9, 95% CI 0.7-1.1, and fully adjusted OR 0.9, 95% CI 0.7-1.1). In conclusion, this study supports the hypothesis that oral disease increases the risk of oesophageal adenocarcinoma, but not for oesophageal squamous cell carcinoma or gastric cancer. Further investigations are warranted.     

The effect of medications which cause inflammation of the gastro‐oesophageal tract on cancer risk: a nested case–control study of routine Scottish data

Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro‐oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro‐oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case–control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro‐oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro‐oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose–response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro‐oesophageal cancer. Our findings should reassure GPs and patients that these widely‐used medications are safe with respect to gastro‐oesophageal cancer risk.     

Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank

Incidence of upper gastrointestinal cancers of the oesophagus and stomach show a strong unexplained male predominance. Hormonal and reproductive factors have been associated with upper gastrointestinal cancers in women but there is little available data on men. To investigate this, we included 219,425 men enrolled in the UK Biobank in 2006–2010. Baseline assessments provided information on hormonal and reproductive factors (specifically hair baldness, number of children fathered, relative age at first facial hair and relative age voice broke) and incident oesophageal or gastric cancers were identified through linkage to U.K. cancer registries. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During 8 years of follow‐up, 309 oesophageal 210 gastric cancers occurred. There was some evidence that male pattern baldness, was associated with gastric cancer risk (adjusted HR 1.35, 95% CI 0.97, 1.88), particularly for frontal male pattern baldness (adjusted HR 1.52, 95% CI 1.02, 2.28). There was little evidence of association between other hormonal and reproductive factors and risk of oesophageal or gastric cancer, overall or by histological subtype. In the first study of a range of male hormonal and reproductive factors and gastric cancer, there was a suggestion that male pattern baldness, often used as a proxy of sex hormone levels, may be associated with gastric cancer. Future prospective studies that directly test circulating sex steroid hormone levels in relation to upper gastrointestinal cancer risk are warranted.     

Toenail trace element status and risk of Barrett's oesophagus and oesophageal adenocarcinoma: results from the FINBAR study

Trace elements have been cited as both inhibitory and causative agents of cancer but importantly exposure to them is potentially modifiable. Our study aimed to examine toenail trace element status and risk of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Toenail clippings from each hallux were obtained from 638 participants of the FINBAR (Factors Influencing the Barrett's Adenocarcinoma Relationship) study comprising 221 healthy controls, 98 reflux oesophagitis, 182 BO and 137 OAC cases. The concentrations of eight toenail trace elements were determined using instrumental neutron activation analysis. Using multivariable adjusted logistic regression analysis, odds ratios (OR) and 95% confidence intervals (CIs) were calculated within tertiles of trace element concentrations. A twofold increased risk of BO was observed, but not OAC, among individuals in the highest tertile of toenail zinc status OR 2.21 (95% CI, 1.11-4.40). A higher toenail selenium status was not associated with risk of OAC OR 0.94 (95% CI, 0.44-2.04) or BO OR 0.89 (95% CI, 0.37-2.12). A borderline significant increased risk of BO was detected with a higher toenail cobalt concentration, OR 1.97 (95% CI, 1.01-3.85). No association was found between toenail levels of chromium, cerium, mercury and OAC or BO risk. This is the first case-control study to investigate a variety of trace elements in relation to OAC and BO risk. Despite antioxidant and proapoptotic properties, no associations were found with selenium. Higher concentrations of toenail zinc and cobalt were associated with an increased BO risk, but not OAC. These findings need confirmation in prospective analysis.     

The influence of needle catheter jejunostomy on weight development after oesophageal cancer surgery in a population-based study.

AIMS: We aimed to assess whether needle catheter jejunostomy (NCJ) influences the weight development or discharge from hospital after oesophageal cancer surgery in an unselected and prospectively collected series of patients. METHODS: Data regarding patients who underwent oesophageal cancer surgery between April 2001 and October 2004 and were followed up until April 2005 were collected from the Swedish Esophageal and Cardia Cancer Register. Details of patient characteristics, including preoperative body weight and length, tumour characteristics, surgical procedures, including NCJ insertion, complications and ward time were obtained. Six months postoperatively the patients responded to a questionnaire that gave information about postoperative weight development. Relative risks were estimated as odds ratios (ORs) calculated with 95% confidence intervals (CIs) using multinomial logistic regression, adjusted for patient and tumour characteristics, type of treatment, type of hospital and occurrence of complications. RESULTS: A total of 233 patients participated, among whom 48% received NCJ. Patients with NCJ had a 42% statistically non-significantly decreased risk of weight loss compared to those without NCJ after adjustment for covariates (OR 0.58; 95% CI 0.25-1.39). Patients with NCJ had a non-statistically significantly longer hospital stay than patients without NCJ, but were seemingly less often discharged to other care homes than their own home compare to the group without NCJ (OR 0.62; 95% CI 0.28-1.38). CONCLUSION: Use of needle catheter jejunostomy might counteract weight loss and facilitate discharge to home after oesophageal cancer resection.     

The contribution of smoking and smokeless tobacco to oesophageal squamous cell carcinoma risk in the African oesophageal cancer corridor: Results from the ESCCAPE multicentre case-control studies

Tobacco use is a well-established risk factor for oesophageal squamous cell carcinoma (ESCC) but the extent of its contribution to the disease burden in the African oesophageal cancer corridor has not been comprehensively elucidated, including by type of tobacco use. We investigated the contribution of tobacco use (smoking and smokeless) to ESCC in Tanzania, Malawi and Kenya. Hospital-based ESCC case-control studies were conducted in the three countries. Incident cases and controls were interviewed using a comprehensive questionnaire which included questions on tobacco smoking and smokeless tobacco use. Logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of ESCC associated with tobacco, adjusted for age, sex, alcohol use, religion, education and area of residence. One thousand two hundred seventy-nine cases and 1345 controls were recruited between August 5, 2013, and May 24, 2020. Ever-tobacco use was associated with increased ESCC risk in all countries: Tanzania (OR 3.09, 95%CI 1.83-5.23), and in Malawi (OR 2.45, 95%CI 1.80-3.33) and lesser in Kenya (OR 1.37, 95%CI 0.94-2.00). Exclusive smokeless tobacco use was positively associated with ESCC risk, in Tanzania, Malawi and Kenya combined (OR 1.92, 95%CI 1.26-2.92). ESCC risk increased with tobacco smoking intensity and duration of smoking. Tobacco use is an important risk factor of ESCC in Tanzania, Malawi and Kenya. Our study provides evidence that smoking and smokeless tobacco cessation are imperative in reducing ESCC risk.     

Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas

Oesophageal and gastric adenocarcinoma share an unexplained male predominance, which would be explained by the hypothesis that oestrogens are protective in this respect. We carried out a nested case-control study of hormone replacement therapy (HRT) among 299 women with oesophageal cancer, 313 with gastric cancer, and 3191 randomly selected control women, frequency matched by age and calendar year in the General Practitioners Research Database in the United Kingdom. Data were adjusted for age, calendar year, tobacco smoking, alcohol consumption, body mass index, hysterectomy, and upper gastrointestinal disorders. Among 1 619 563 person-years of follow-up, more than 50% reduced risk of gastric adenocarcinoma was found among users of HRT compared to nonusers (odds ratio (OR), 0.48, 95% confidence interval (CI) 0.29-0.79). This inverse association appeared to be stronger for gastric noncardia (OR 0.34, 95% CI 0.14-0.78) and weaker for gastric cardia tumours (OR 0.68, 95% CI 0.23-2.01). There was no association between HRT and oesophageal adenocarcinoma (OR 1.17, 95% CI 0.41-3.32).     

β-Blocker usage and colorectal cancer mortality: a nested case–control study in the UK Clinical Practice Research Datalink cohort

BackgroundEpidemiological and laboratory studies suggest that β-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic β-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort.Patients and methods: A nested case–control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to β-blocker usage (data from GP-prescribing records).ResultsPost-diagnostic β-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78–1.02). Similar associations were found when analysing drug frequency, β-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in β-blocker users (adjusted OR = 0.88; 95% CI 0.77–1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40–0.97; P = 0.04).ConclusionsIn this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic β-blocker use and colorectal cancer-specific mortality.Clinical Trials numberNCT00888797.     

Hormone replacement therapy and oral contraceptives and risk of oesophageal adenocarcinoma: A systematic review and meta‐analysis

There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results. We conducted a systematic literature search and meta‐analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel–Haenszel random‐effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR = 0.75; 95% CI: 0.58–0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR = 0.76; 95% CI: 0.57–1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted.     

Morning chronotype and digestive tract cancers: Mendelian randomization study

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome-wide significance level (P < 5 × 10⁻⁸) were used as instrumental variables from a genome-wide meta-analysis of 449 734 individuals. Summary-level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta-analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90-0.98), stomach cancer (OR 0.84, 95% CI: 0.73-0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87-0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers.     

Association between Dietary Factors and Breast Cancer Risk among Chinese Females: Systematic Review and Meta-analysis

Background: Evidence for associations between dietary factors and breast cancer risk is inconclusive amongChinese females. To evaluate this question, we conducted a systematic review of relevant case-control and cohortstudies. Methods: Studies were systematically searched among 5 English databases (PudMed, ScienceDirect,Wiley, Clinicaltrials.gov, and Cochrane) and 3 Chinese databases (CNKI, WanFang, and VIP) until November2012. Random effects models were used to estimate summary odds ratios (ORs) and the corresponding 95%confidence intervals (CIs). Results: Thirty one case-control studies and two cohort studies involving 9,299 casesand 11,413 controls were included. Consumption of both soy and fruit was significantly associated with decreasedrisk of breast cancer, with summary ORs of 0.65 (95% CIs: 0.43–0.99; I2=88.9%, P<0.001; N=13) and 0.66(95% CIs: 0.47–0.91; I2=76.7%, P<0.001; N=7), respectively. Consumption of fat was significantly associatedwith increased risk of breast cancer (OR=1.36; 95% CIs: 1.13–1.63; I2=47.9%, P=0.088; N=6). There was nonsignificantassociation between consumption of vegetables and breast cancer risk (OR=0.72; 95% CIs: 0.51–1.02; I2= 74.4%, P<0.001; N=9). However, sensitivity analysis based on adjusted ORs showed decreased risk of breastcancer was also associated with consumption of vegetables (OR=0.49; 95% CIs: 0.30-0.67). Conclusion: Bothsoy food and fruit are significantly associated with decreased risk of breast cancer among Chinese females, andvegetables also seems to be protective while dietary fatexerts a promoting influence.     

Reproductive and sex hormonal factors and oesophageal and gastric junction adenocarcinoma: A pooled analysis

BackgroundThe rapidly rising incidence and the striking male predominance are as yet unexplained features of oesophageal and gastric junction adenocarcinoma. Few and underpowered studies have examined the impact of female reproductive factors on risk of these adenocarcinomas in women. We therefore pooled data on women from four population-based case-control studies to examine the association of female reproductive and sex hormonal factors with oesophageal and gastric junction adenocarcinoma.MethodsData on women from case-control studies conducted in Ireland, the United Kingdom (UK), Australia and United States of America (USA) were pooled. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a range of reproductive factors, adjusted for age, study and major risk factors for oesophageal and gastric junction adenocarcinoma.ResultsWe included 218 cases and 862 controls. Among parous women, a reduced risk of oesophageal and gastric junction adenocarcinoma was found after breastfeeding (OR = 0.58, 95% CI = 0.37–0.92) and the risk decreased with increased duration of breastfeeding (>12 months OR = 0.42, 95% CI = 0.23–0.77). The endogenous reproductive factors such as parity, menstruation, history of pregnancy and the exogenous factors such as use of oral contraceptives and of hormone replacement therapy were not statistically significantly associated with oesophageal and gastric junction adenocarcinoma.ConclusionOur findings suggest that breastfeeding is associated with a decreased risk of oesophageal and gastric junction adenocarcinoma. The potential mechanism of this association warrants further investigation.     

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site

Background To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site.Methods A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed.Results The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65).Conclusion Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.Subject terms: Risk factors, Epidemiology     

Family history of hormonal cancers and colorectal cancer risk: A case‐control study conducted in Ontario

Aggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well‐described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first‐degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk. Population‐based CRC cases and controls were recruited by the Ontario Familial Colorectal Cancer Registry (OFCCR). Logistic regression was conducted to obtain odds ratio (OR) estimates and 95% confidence intervals (95% CIs). First‐degree family history of breast cancer was associated with a modest, borderline statistically significant increased CRC risk (age‐, sex‐adjusted OR = 1.2, 95% CI = 1.0, 1.5). The magnitude of CRC risk was greatest if more than one first‐degree kin had breast cancer (age‐, sex‐adjusted OR = 1.7, 95% CI = 1.0, 2.0), as well as if the kin was diagnosed at >50 years of age (age‐, sex‐adjusted OR = 1.4, 95% CI = 1.1, 1.8). Family history of ovarian cancer was associated with reduced CRC risk (multivariate‐adjusted OR = 0.6, 95% CI = 0.3, 1.0). Although statistically significant increases in CRC risk were observed in the age‐, sex‐adjusted OR estimates for family history of endometrial and prostate cancers, the associations were no longer significant after multivariate‐adjustment. In conclusion, individuals with a first‐degree kin with breast cancer may have a modest increased risk for CRC compared to individuals without. © 2009 UICC     

Risk factors for oesophageal cancer in northeast China

A hospital-based case-control study of oesophageal cancer was carried out in the Heilongjiang Province, a low-risk area for oesophageal cancer in China. From May 1985 to May 1989, 196 histologically confirmed cases and 392 controls with other (non-neoplastic) diseases were personally interviewed in the wards of 5 major hospitals. Information was obtained about usual consumption in the early 1980s of 32 major contributors to the diet in the province, socio-demographic status, smoking and alcohol consumption. Odds ratios (OR) were obtained from logistic regression models, and confounding was controlled by means of multivariate models. Smoking and alcohol consumption were major risk factors for oesophageal cancer in this population. Smokers of handmade cigarettes exhibited a particularly high risk. A near multiplicative synergism was found between smoking and alcohol consumption. There was a significant inverse dose-risk trend for combined consumption of vegetables and fruits; a 300-g increase per day lowered risk by 35%. Vitamin C intake was negatively associated with risk; a 100-mg increase per day lowered risk by 39%. Our data suggest a modifying effect of vitamin C and β-carotene on risk associated with smoking, but the power of analyses was low. Salt, salt-preserved foods and pickled vegetables were not associated with increased risk. High temperature of meals and drinks was a strong risk indicator in this population. The strength of tea and overall tea consumption were independent determinants of the risk. © Wiley-Liss, Inc.     

Combined effects of the p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer in never-smokers

Because p53 and p73 are associated with critical cellular processes and can be inactivated or degraded by the human papillomavirus (HPV) E6 oncoprotein, we investigated the combined effects of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer. We analyzed genotype data from 326 patients with squamous cell carcinoma of the oral cavity or oropharynx and 349 cancer-free controls. We found that HPV16 seropositivity was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.42; 95% confidence interval (CI), 2.28-5.13], especially among never-smokers (adjusted OR, 8.20; 95% CI, 3.66-18.4) and subjects with variant genotypes [adjusted OR for p53 Arg/Pro + Pro/Pro (Pro carriers), 5.00; 95% CI, 2.72-9.21; adjusted OR for p73 GC/AT + AT/AT (AT carriers), 3.83; 95% CI, 1.98-7.41]. HPV16 seropositivity was also associated with an significantly increased risk of oral cancer in all three risk groups with combined genotypes [adjusted ORs (95% CIs) were 2.28 (1.15-4.54) for p53 Arg/Arg and p73 GC/GC, the low-risk group; 3.97 (2.14-7.36) for p53 Arg/Arg and p73 AT carriers or p53 Pro carriers and p73 GC/GC, the medium-risk group and 5.11 (2.00-13.0) for p53 Pro carriers and p73 AT carriers, the high-risk group]. Moreover, HPV16-seropositive never-smokers in the high-risk group exhibited an approximately 11-fold greater risk of oral cancer (adjusted OR, 11.3; 95% CI, 1.22-106.0) than did HPV16-seronegative never-smokers in the low-risk group. These findings suggest that the combined variants of p53 and p73 significantly increase the risk of HPV16-associated oral cancer, especially among never-smokers.     

The role of socio-economic status in the decision making on diagnosis and treatment of oesophageal cancer in The Netherlands

In the United States (USA), a correlation has been demonstrated between socio-economic status (SES) of patients on the one hand, and tumour histology, stage of the disease and treatment modality of various cancer types on the other hand. It is unknown whether such correlations are also involved in patients with oesophageal cancer in The Netherlands. Between 1994 and 2003, 888 oesophageal cancer patients were included in a prospective database with findings on the diagnostic work-up and treatment of oesophageal cancer. Socio-economic status of patients was defined as the average net yearly income. Linear-by-linear association testing revealed that oesophageal adenocarcinoma was more frequently observed in patients with higher SES and squamous cell carcinoma in patients with lower SES (P=0.02). Multivariable logistic regression analysis showed no correlation between SES and staging procedures and preoperative TNM stage. The adjusted odds ratio (OR) for stent placement was 0.82 (95% CI 0.71-0.95), indicating that with an increase in SES by 1200 [euro], the likelihood that a stent was placed declined by 18%. Patients with a higher SES more frequently underwent resection or were treated with chemotherapy (OR: 1.15; 95% CI 1.01-1.32 and OR: 1.16; 95% CI 1.02-1.32, respectively). Socio-economic factors are involved in oesophageal cancer in The Netherlands, as patients with a higher SES are more likely to have an adenocarcinoma and patients with a lower SES a squamous cell carcinoma. Moreover, the correlations between SES and different treatment modalities suggest that both patient and doctor determinants contribute to the decision on the most optimal treatment modality in patients with oesophageal cancer.