Nirmala Pandeya

Global burden of cancer attributable to high body-mass index in 2012: a population-based study

BACKGROUND High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012. METHODS In this population-based study, we derived population attributable fractions (PAFs) using relative risks and BMI estimates in adults by age, sex, and country. Assuming a 10-year lag-period between high BMI and cancer occurrence, we calculated PAFs using BMI estimates from 2002 and used GLOBOCAN2012 data to estimate numbers of new cancer cases attributable to high BMI. We also calculated the proportion of cancers that were potentially avoidable had populations maintained their mean BMIs recorded in 1982. We did secondary analyses to test the model and to estimate the effects of hormone replacement therapy (HRT) use and smoking. FINDINGS Worldwide, we estimate that 481,000 or 3.6% of all new cancer cases in adults (aged 30 years and older after the 10-year lag period) in 2012 were attributable to high BMI. PAFs were greater in women than in men (5.4% vs 1.9%). The burden of attributable cases was higher in countries with very high and high human development indices (HDIs; PAF 5.3% and 4.8%, respectively) than in those with moderate (1.6%) and low HDIs (1.0%). Corpus uteri, postmenopausal breast, and colon cancers accounted for 63.6% of cancers attributable to high BMI. A quarter (about 118,000) of the cancer cases related to high BMI in 2012 could be attributed to the increase in BMI since 1982. INTERPRETATION These findings emphasise the need for a global effort to abate the increasing numbers of people with high BMI. Assuming that the association between high BMI and cancer is causal, the continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer. FUNDING World Cancer Research Fund International, European Commission (Marie Curie Intra-European Fellowship), Australian National Health and Medical Research Council, and US National Institutes of Health.

Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus

Objective: To measure the relative risks of adenocarcinomas of the oesophagus and gastro-oesophageal junction associated with measures of obesity, and their interactions with age, sex, gastro-oesophageal reflux symptoms and smoking. Design and setting: Population-based case–control study in Australia. Patients: Patients with adenocarcinomas of the oesophagus (n = 367) or gastro-oesophageal junction (n = 426) were compared with control participants (n = 1580) sampled from a population register. Main outcome measure: Relative risk of adenocarcinoma of the oesophagus or gastro-oesophageal junction. Results: Risks of oesophageal adenocarcinoma increased monotonically with body mass index (BMI) (ptrend <0.001). Highest risks were seen for BMI ⩾40 kg/m2 (odds ratio (OR) = 6.1, 95% CI 2.7 to 13.6) compared with “healthy” BMI (18.5–24.9 kg/m2). Adjustment for gastro-oesophageal reflux and other factors modestly attenuated risks. Risks associated with obesity were substantially higher among men (OR = 2.6, 95% CI 1.8 to 3.9) than women (OR = 1.4, 95% CI 0.5 to 3.5), and among those aged <50 years (OR = 7.5, 95% CI 1.7 to 33.0) than those aged ⩾50 years (OR = 2.2, 95% CI 1.5 to 3.1). Obese people with frequent symptoms of gastro-oesophageal reflux had significantly higher risks (OR = 16.5, 95% CI 8.9 to 30.6) than people with obesity but no reflux (OR = 2.2, 95% CI 1.1 to 4.3) or reflux but no obesity (OR = 5.6, 95% 2.8 to 11.3), consistent with a synergistic interaction between these factors. Similar associations, but of smaller magnitude, were seen for gastro-oesophageal junction adenocarcinomas. Conclusions: Obesity increases the risk of oesophageal adenocarcinoma independently of other factors, particularly among men. From a clinical perspective, these data suggest that patients with obesity and frequent symptoms of gastro-oesophageal reflux are at especially increased risk of adenocarcinoma.

Prolonged Prevention of Squamous Cell Carcinoma of the Skin by Regular Sunscreen Use

Half of all cancers in the United States are skin cancers. We have previously shown in a 4.5-year randomized controlled trial in an Australian community that squamous cell carcinomas (SCC) but not basal cell carcinomas (BCC) can be prevented by regular sunscreen application to the head, neck, hands, and forearms. Since cessation of the trial, we have followed participants for a further 8 years to evaluate possible latency of preventive effect on BCCs and SCCs. After prolonged follow-up, BCC tumor rates tended to decrease but not significantly in people formerly randomized to daily sunscreen use compared with those not applying sunscreen daily. By contrast, corresponding SCC tumor rates were significantly decreased by almost 40% during the entire follow-up period (rate ratio, 0.62; 95% confidence interval, 0.38-0.99). Regular application of sunscreen has prolonged preventive effects on SCC but with no clear benefit in reducing BCC. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2546–8)

Cigarette Smoking and Adenocarcinomas of the Esophagus and Esophagogastric Junction: A Pooled Analysis From the International BEACON Consortium

BACKGROUND Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation. METHODS We used primary data from 10 population-based case-control studies and two cohort studies from the Barretts Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided. RESULTS The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and > or =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar. CONCLUSIONS Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.

Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn’s disease

Background and aims: Recent studies on appendicectomy rates in ulcerative colitis and Crohn’s disease have generally not addressed the effect of appendicectomy on disease characteristics. The aims of this study were to compare appendicectomy rates in Australian inflammatory bowel disease patients and matched controls, and to evaluate the effect of prior appendicectomy on disease characteristics. Methods: Patients were ascertained from the Brisbane Inflammatory Bowel Disease database. Controls matched for age and sex were randomly selected from the Australian Twin Registry. Disease characteristics included age at diagnosis, disease site, need for immunosuppression, and intestinal resection. Results: The study confirmed the significant negative association between appendicectomy and ulcerative colitis (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.14–0.38; p<0.0001) and found a similar result for Crohn’s disease once the bias of appendicectomy at diagnosis was addressed (OR 0.34, 95% CI 0.23–0.51; p<0.0001). Prior appendicectomy delayed age of presentation for both diseases and was statistically significant for Crohn’s disease (p=0.02). In ulcerative colitis, patients with prior appendicectomy had clinically milder disease with reduced requirement for immunosuppression (OR 0.15, 95% CI 0.02–1.15; p=0.04) and proctocolectomy (p=0.02). Conclusions: Compared with patients without prior appendicectomy, appendicectomy before diagnosis delays disease onset in ulcerative colitis and Crohn’s disease and gives rise to a milder disease phenotype in ulcerative colitis.

Steatosis and chronic hepatitis C: analysis of fibrosis and stellate cell activation

BACKGROUND/AIMS Steatosis is a frequent histological finding in chronic hepatitis C and is associated with increased hepatic fibrosis. METHODS We studied 80 patients with untreated chronic hepatitis C to determine whether steatosis contributes to fibrosis through a steatohepatitis-like pathway. RESULTS Fine sinusoidal and/or central vein fibrosis was present in 52 patients (65%). This was typically located in acinar zone 3 and had a chicken-wire appearance similar to that seen in steatohepatitis. A statistically significant relationship was found between subsinusoidal fibrosis and age (r(s) = 0.33, P = 0.003) and grade of steatosis (r(s) = 0.35, P = 0.001). Mean body mass index was higher in patients with focal (28.4 +/- 4.7 kg/m2) or extensive (29.6 +/- 5.9 kg/m2) subsinusoidal fibrosis than in those patients with no subsinusoidal fibrosis (25.5 +/- 3.7 kg/m2). The extent of alpha-smooth muscle actin staining (as a marker of stellate cell activation) correlated with the degree of portal inflammation and the stage of portal fibrosis, but not with the grade of hepatic steatosis. CONCLUSIONS These findings suggest that in hepatitis C infection, host factors, particularly adiposity, contribute to both steatosis and acinar fibrosis. The implication of these observations is that weight reduction may provide an important therapeutic strategy for patients with chronic hepatitis C.

Control of scabies, skin sores and haematuria in children in the Solomon Islands: another role for ivermectin

OBJECTIVE To assess the effects of a 3-year programme aimed at controlling scabies on five small lagoon islands in the Solomon Islands by monitoring scabies, skin sores, streptococcal skin contamination, serology and haematuria in the island children. METHODS Control was achieved by treating almost all residents of each island once or twice within 2 weeks with ivermectin (160-250 microg/kg), except for children who weighed less than 15 kg and pregnant women, for whom 5% permethrin cream was used. Reintroduction of scabies was controlled by treating returning residents and visitors, whether or not they had evident scabies. FINDINGS Prevalence of scabies dropped from 25% to less than 1% (P < 0.001); prevalence of sores from 40% to 21% (P < 0.001); streptococcal contamination of the fingers in those with and without sores decreased significantly (P = 0.02 and 0.047, respectively) and anti-DNase B levels decreased (P = 0.002). Both the proportion of children with haematuria and its mean level fell (P = 0.002 and P < 0.001, respectively). No adverse effects of the treatments were seen. CONCLUSION The results show that ivermectin is an effective and practical agent in the control of scabies and that control reduces the occurrence of streptococcal skin disease and possible signs of renal damage in children. Integrating community-based control of scabies and streptococcal skin disease with planned programmes for controlling filariasis and intestinal nematodes could be both practical and produce great health benefits.

Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia.

Objective To measure the effectiveness of the quadrivalent human papillomavirus (HPV) vaccine against cervical abnormalities four years after implementation of a nationally funded vaccination programme in Queensland, Australia. Design Case-control analysis of linked administrative health datasets. Setting Queensland, Australia. Participants Women eligible for free vaccination (aged 12-26 years in 2007) and attending for their first cervical smear test between April 2007 and March 2011. High grade cases were women with histologically confirmed high grade cervical abnormalities (n=1062) and “other cases” were women with any other abnormality at cytology or histology (n=10 887). Controls were women with normal cytology (n=96 404). Main outcome measures Exposure odds ratio (ratio of odds of antecedent vaccination (one, two, or three vaccine doses compared with no doses) among cases compared with controls), vaccine effectiveness ((1−adjusted odds ratio)×100), and number needed to vaccinate to prevent one cervical abnormality at first screening round. We stratified by four age groups adjusted for follow-up time, year of birth, and measures of socioeconomic status and remoteness. The primary analysis concerned women whose first ever smear test defined their status as a case or a control. Results The adjusted odds ratio for exposure to three doses of HPV vaccine compared with no vaccine was 0.54 (95% confidence interval 0.43 to 0.67) for high grade cases and 0.66 (0.62 to 0.70) for other cases compared with controls with normal cytology, equating to vaccine effectiveness of 46% and 34%, respectively. The adjusted numbers needed to vaccinate were 125 (95% confidence interval 97 to 174) and 22 (19 to 25), respectively. The adjusted exposure odds ratios for two vaccine doses were 0.79 (95% confidence interval 0.64 to 0.98) for high grade cases and 0.79 (0.74 to 0.85) for other cases, equating to vaccine effectiveness of 21%. Conclusion The quadrivalent HPV vaccine conferred statistically significant protection against cervical abnormalities in young women who had not started screening before the implementation of the vaccination programme in Queensland, Australia.

Alcohol Consumption and the Risks of Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus

BACKGROUND AND AIMS Alcohol has been declared a carcinogen for cancers of the esophagus, although the evidence relates largely to the squamous subtype. Evidence for an effect on adenocarcinomas is scant and inconsistent. METHODS We compared nationwide samples of patients with esophageal adenocarcinoma (EAC) (n=365) or esophagogastric junction adenocarcinoma (EGJAC) (n=426) or esophageal squamous cell carcinoma (ESCC) (n=303) with controls sampled from a population register (n=1580). We used generalized additive models to assess nonlinear effects of self-reported alcohol intake on cancer risk, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic and piecewise regression. RESULTS We observed no association between average weekly alcohol intake and EAC or EGJAC risk. For ESCC, the relationship with alcohol was nonlinear. At intakes of less than 170 g/wk there was no significant association; at greater than this level, there was a significant linear effect (OR, 1.03; 95% CI, 1.02-1.05 per 10 g alcohol/wk). For ESCC, but not EAC or EGJAC, a statistically significant multiplicative interaction between smoking and alcohol was observed (P=.02). In analyses by beverage type, ESCC risks, but not EAC or EGJAC, increased linearly with beer intake (OR, 1.05; 95% CI, 1.04-1.07). Those who drank modest levels of wine (<50-90 g/wk) or port or spirits (<10-20 g/wk) had significantly lower risks of all 3 cancers than nondrinkers; higher intakes were associated with increased risks of ESCC only. CONCLUSIONS Alcohol intake above the recommended US dietary guidelines significantly increases the risk of ESCC, but not EAC or EGJAC. Smoking modifies the effect of alcohol intake on ESCC risk.

Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium

Background Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms. Methods Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m2) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender. Results The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI ≥40 was associated with both OA (OR 4.76, 95% CI 2.96–7.66) and OGJA (OR 3.07, 95% CI 1.89–4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk. Conclusions These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA.