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Current information on the out‐of‐pocket costs incurred by Australians being treated for cancer is limited. We therefore investigated these costs for participants in the QSkin Sun and Health Study...

Hysterectomy is a common gynecological procedure, particularly in middle and high income countries. The aim of this paper was to describe and examine hysterectomy trends in Australia from 2000-2001 to 2013-2014. For women aged 25 years and over, data on the number of hysterectomies performed in Australia annually were sourced from the National Hospital and Morbidity Database. Age-specific and age-standardized hysterectomy rates per 10 000 women were estimated with adjustment for hysterectomy prevalence in the population. Using joinpoint regression analysis, we estimated the average annual percentage change over the whole study period (2000-2014) and the annual percentage change for each identified trend line segment. A total of 431 162 hysterectomy procedures were performed between 2000-2001 and 2013-2014; an annual average of 30 797 procedures (for women aged 25+ years). The age-standardized hysterectomy rate, adjusted for underlying hysterectomy prevalence, decreased significantly over the whole study period [average annual percentage change -2.8%; 95% confidence interval (CI) -3.5%, -2.2%]. The trend was not linear with one joinpoint detected in 2008-2009. Between 2000-2001 and 2008-2009 there was a significant decrease in incidence (annual percentage change -4.4%; 95% CI -5.2%, -3.7%); from 2008-2009 to 2013-2014 the decrease was minimal and not significantly different from zero (annual percentage change -0.1%; 95% CI -1.7%, 1.5%). A similar change in trend was seen in all age groups. Hysterectomy rates in Australian women aged 25 years and over have declined in the first decade of the 21st century. However, in the last 5 years, rates appear to have stabilized.

Aims.There is limited longitudinal research that has looked at the longer term incidence of depressive symptoms, comparing women with a hysterectomy to women without a hysterectomy. We aimed to investigate the association between hysterectomy status and the 12-year incidence of depressive symptoms in a mid-aged cohort of Australian women, and whether these relationships were modified by use of exogenous hormones.Methods.We used generalised estimating equation models for binary outcome data to assess the associations of the incidence of depressive symptoms (measured by the 10-item Centre for Epidemiologic Studies Depression Scale) across five surveys over a 12-year period, in women with a hysterectomy with ovarian conservation, or a hysterectomy with bilateral oophorectomy compared with women without a hysterectomy. We further stratified women with hysterectomy by their current use of menopausal hormone therapy (MHT). Women who reported prior treatment for depression were excluded from the analysis.Results.Compared with women without a hysterectomy (n = 4002), both women with a hysterectomy with ovarian conservation (n = 884) and women with a hysterectomy and bilateral oophorectomy (n = 450) had a higher risk of depressive symptoms (relative risk (RR) 1.20; 95% confidence interval (CI) 1.06–1.36 and RR 1.44; 95% CI 1.22–1.68, respectively). There were differences in the strength of the risk for women with a hysterectomy with ovarian conservation, compared with those without, when we stratified by current MHT use. Compared with women without a hysterectomy who did not use MHT, women with a hysterectomy with ovarian conservation who were also MHT users had a higher risk of depressive symptoms (RR 1.57; 95% CI 1.31–1.88) than women with a hysterectomy with ovarian conservation but did not use MHT (RR 1.17; 95% CI 1.02–1.35). For women with a hysterectomy and bilateral oophorectomy, MHT use did not attenuate the risk. We could not rule out, however, that the higher risk seen among MHT users may be due to confounding by indication, i.e. MHT was prescribed to treat depressive symptoms, but their depressive symptoms persisted.Conclusions.Women with a hysterectomy (with and without bilateral oophorectomy) have a higher risk of new incidence of depressive symptoms in the longer term that was not explained by lifestyle or socio-economic factors.

Cutaneous melanomas are postulated to arise through at least two causal pathways, namely the "chronic sun exposure" and "nevus" pathways. While chronic sun exposure probably causes many head/neck melanomas, its role at other sites is unclear. In a population-based, case-case comparison study conducted in Brisbane, Australia, we determined the prevalence and epidemiologic correlates of chronic solar damage in skin adjacent to invasive, incident melanomas on the trunk (n-=-418) or head/neck (n-=-92) among patients aged 18-79 in 2007-2010. Participants self-reported information about environmental and phenotypic factors, and a dermatologist counted nevi and actinic keratoses. Dermatopathologists assessed solar elastosis adjacent to each melanoma using a four-point scale (nil, mild, moderate, marked), and noted the presence or absence of adjacent neval remnants. We measured associations between various factors and solar elastosis using polytomous logistic regression. Marked or moderate solar elastosis was observed in 10% and 27%, respectively, of trunk melanomas, and 60% and 17%, respectively, of head/neck melanomas. At both sites, marked elastosis was positively associated with age (p

Background and Objectives: Naevi may change in size, shape and colour due to multiple inherent and external factors. We observed naevi changing size in adults at high risk of melanoma, and assessed associations of change with demographic factors, skin type, sites of naevi and history of melanoma. Methods: In total, 29 participants with a personal or first-degree family history of melanoma or those deemed at high risk with multiple naevi of variable morphologies had all melanocytic naevi 0.5-1cm imaged and their maximum diameter recorded. Maximum diameters from repeat imaging of naevi 12 months later were compared to baseline measurements. Newly appearing naevi ≥5mm and naevi that grew or decreased in size by 20% or more were defined as changeable naevi. Associations between changeable naevi and participants' age, sex, skin type, body sites of naevi and personal and family history of melanoma were assessed. Results: There was no difference in changeable naevus rates among sex, age or skin type. Among the body sites, the head and neck were most likely to have changeable naevi, and the upper limbs the least likely. A family history of melanoma almost tripled the likelihood of having changeable naevi compared with those without both personal and family melanoma history. Conclusions: Naevi can continue to change in size throughout adulthood, showing both increases and decreases in size as well as the appearance of new naevi. This has important clinical implications, in particular for sequential body imaging used for the detection of melanoma.

Importance Concerns around possible overdiagnosis and overtreatment of differentiated thyroid cancer (DTC) have been raised. Issues concerning health-related quality of life (HRQOL) after diagnosis and treatment of DTC are understudied in this patient group. Objective To better understand the range of HRQOL outcomes, including possible adverse effects of treatment, associated with diagnosis and treatment of DTC and whether these outcomes vary by type of surgery received. Design, Setting, and Participants This content analysis assessed responses to an open-ended question about outcomes and concerns after DTC diagnosis and treatment among patients ascertained from the major postsurgical thyroid cancer treatment center and the population-based Cancer Registry in Queensland, Australia. Participants were aged 18 to 79 years and recently diagnosed with throid cancer. Responses underwent analysis to identify and code emergent themes to describe HRQOL issues and adverse effects of treatment experienced. Quantitative analysis was used to explore whether surgery type was associated with HRQOL issues and/or adverse effects of treatment. Of 1416 eligible patients, 1005 (71.0%) participated. Data were collected from July 1, 2013, through August 31, 2016, and analyzed from January 11 through April 9, 2018. Main Outcomes and Measures Issues concerning HRQOL. Results The analysis included 1005 patients (72.2% female [n = 726]; mean [SD] age, 52 [14.0 years) with DTC. Most patients were diagnosed with papillary thyroid cancer (889 of 1003 [88.6%]), had tumors smaller than 2 cm in size (564 of 1000 [56.4%]), and received a total thyroidectomy (791 of 1005 [78.7%]). Overall, 775 patients (77.1%) reported HRQOL issues after diagnosis and treatment of DTC. The following 4 main themes emerged from content analysis of patient responses: physical (663 [66.0%]), psychological (187 [18.6%]), lifestyle (82 [8.2%]), and no issue or adverse effect (246 [24.5%]). Patients who had a total thyroidectomy (without neck dissection) were 1.5 times (odds ratio, 1.49; 95% CI, 1.04-2.12) more likely to report an HRQOL issue or an adverse effect of treatment compared with patients who underwent a hemithyroidectomy. Conclusions and Relevance According to results of this study, patients diagnosed with DTC report wide-ranging HRQOL issues; these are more prevalent among patients who have total thyroidectomies rather than hemithyroidectomies. For patients with small, localized DTCs, hemithyroidectomy may offer fewer adverse effects of treatment and better HRQOL outcomes than total thyroidectomy. It appears that issues with HRQOL should be considered by patients and physicians when deciding on the best treatment approach after a diagnosis of DTC.

Objective : Alcohol and tobacco are the two major established environmental factors associated with squamous cell carcinoma of the esophagus (ESCC). However, the prevalence of these exposures differs substantially between men and women. Moreover, the prevalence of smoking has declined in recent years, whereas per capita consumption of alcohol has remained steady in both sexes. Quantifying the burden of ESCC attributable to these causal factors is necessary to inform potential preventive strategies. Methods : We estimated the population attributable fraction (PAF) of ESCC due to smoking and alcohol, using data from an Australian population based case–control study (305 ESCC cases, 1554 controls). Results : Estimated PAF for ESCC were 49% (95% CI: 38–60) and 32% (95% CI: 25–40) due to smoking and heavy alcohol consumption respectively. More than 75% of the ESCC burden in men could be attributed to smokers with heavy alcohol consumption. The highest burden was among ≥30 pack years smokers who also consumed alcohol heavily (>17 drinks/week); this differed significantly between men (PAF 36%, 95% CI 29–44) and women (PAF 5%, 95% CI 2–10). Among women only, low intakes of fruit and vegetables accounted for about 9% of the ESCC burden. Conclusion : The burden of ESCC attributable to smoking combined with heavy alcohol consumption is remarkably high in men. In women, the burden of ESCC due to these factors is lower, and poor nutrition may also play a role.

STUDY QUESTION Are parity and the timing of menarche associated with premature and early natural menopause? SUMMARY ANSWER Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP

Tobacco smoking is a strong risk factor for cancer, but associations with basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) of the skin have been inconsistent. We prospectively investigated the associations between cigarette smoking and 3-year incidence of first primary BCC or SCC in the QSkin cohort (n=43765). Smoking history was self-reported at baseline; newly diagnosed and surgically treated BCCs and SCCs were ascertained through linkage to the national health insurance scheme and verified by histopathology reports. We restricted our analyses to white participants who at baseline reported no past history of skin cancer excisions or cutaneous melanoma (registry-confirmed) and no more than 5 destructively-treated skin lesions (n=18830). Cox proportional hazards regression analysis was used to examine the association between smoking status and risk of BCC and SCC, adjusted for demographic and phenotypic characteristics and sun exposure history. Current smokers had significantly lower risks of BCC (HR 0.6; 95% CI, 0.4-0.9) but significantly increased risks of SCC (HR 1.9; 95% CI, 1.1-3.1) compared with never smokers. Former smoking was not associated. In analyses restricted to people with no past history of destructively-treated lesions (n=13323), we found a non-significant decreased risk of BCC (HR 0.8; 95% CI, 0.5-1.3) and a significant increased risk of SCC (HR 2.3; 95% CI, 1.3-4.4) among current smokers compared to never smokers. Future analyses will investigate associations with age at initiation, duration and intensity of smoking, and time since quitting. These findings suggest current smoking is a risk factor for cutaneous SCC but not BCC.

The costs of diagnosing and treating basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the highest of all cancers in Australia. However, information regarding incidence, multiplicity and risk are scarce as keratinocyte cancers (KCs) are not captured by most registries. To address these gaps, we initiated the QSKIN Study in 2010 recruiting 43,794 Queensland residents from a population register (participation 24%). Participants self-completed a baseline survey recording information on residential history, sun exposure, phenotype and medical and family history. We identified keratinocyte cancers through linkage to the national insurance register, confirming histopathology where possible. During the first three years of follow-up, 6936 (17%) participants had at least one KC excised; 1626 (4%) had 3 or more excisions. Of lesions with known histology, there were 9713 BCCs (in 4080 people) and 3505 SCCs (in 1782 people). We developed a tool to predict the risk of developing KC using backwards stepwise logistic regression models. The primary model retained terms for 10 items, including history of >20 prior skin cancers excised (OR 8.6), >50 skin lesions destroyed (OR 3.4), age >70 years (OR 3.5) and fair skin color (OR 1.8). Discrimination was high (Area under ROC 0.80, 95%CI 0.79-0.81) and the model appeared well calibrated. Among those reporting no prior history of skin cancer, a model with 10 factors (including age, sex, ethnicity and phenotypic factors) predicted KC events with reasonable discrimination (AUROC 0.72, 95% CI 0.70-0.75). The tool is undergoing external validation in primary care skin cancer clinics.

Estrogens have photosensitizing properties, but few prospective studies have examined the relationship between hormonal and reproductive factors and incidence of basal cell carcinoma (BCC) in women. Previous findings have been inconsistent, particularly in relation to parity and use of oral contraceptives (OCs) and menopausal hormone therapy (MHT). Given the heterogeneity in the literature, we sought to examine the association between hormonal and reproductive factors and BCC risk in a cohort of women (n=23,879) enrolled in the QSkin Study in 2011. The baseline survey included questions about use of OCs and MHT, age at menarche, menopausal status, age at menopause and parity. We restricted our analysis to white women with no past history of treatments for skin cancer and less than 6 treatments for actinic keratoses (n=11,204) and used Cox proportional hazards models to estimate the hazards ratio associated with each potential hormonal/reproductive factor and first histologically confirmed BCC, while taking account of the potentially confounding influence of sun exposure history, phenotypic characteristics, body mass index and smoking history. During a median follow-up duration of 2.95 years, 352 women developed BCC. In preliminary analyses, amongst post-menopausal women, ever use of MHT at baseline was associated with an increased risk of developing BCC compared to never users (adjusted HR1.4; 95%CI 1.1-1.9), but risk did not differ by duration of use. We found no association between parity, age at menarche, age at menopause or use of OCs and BCC incidence. Future work will examine whether MHT use is associated with an increased risk of a second primary BCC.

Frequent gastroesophageal reflux (GER) causes chronic inflammation and damages esophageal mucosa, which can lead to Barrett's esophagus. It has also been consistently found to be a strong risk factor for esophageal adenocarcinoma. The prevalence of GER appears to vary; however, population-based Australian studies investigating the symptoms are limited. This study aimed to estimate the population prevalence and identify the determinants of frequent GER symptoms in the Australian population. Self-reported information on the frequency of reflux symptoms were collected from 1,580 adults from a population register. We estimated age- and sex-standardized prevalence of occasional (

Aliment Pharmacol Ther 2011; 34: 1235–1244 Summary Background Epidemiological studies have consistently reported inverse associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and oesophageal adenocarcinoma, but few have investigated associations with the precursor lesion, Barrett’s oesophagus. Aim To investigate the relationship between NSAID use and risk of Barrett’s oesophagus. Methods We conducted a large population-based case-control study that collected information on patterns of intake for aspirin and non-aspirin NSAIDs during the past 5 years and other exposures from 285 patients with nondysplastic Barrett’s oesophagus, 108 patients with dysplastic Barrett’s oesophagus, and two separate control groups: 313 endoscopy patients with acute inflammatory changes (‘inflammation controls’) and 644 population controls. We calculated odds ratios (ORs) and 95% CIs using unconditional logistic regression. Results Use of aspirin was not associated with nondysplastic Barrett’s oesophagus when compared with population (OR = 1.01, 95% CI 0.71–1.43) or inflammation controls (OR = 1.16, 95% CI 0.80–1.68). Whereas we observed significant risk reductions for use of non-aspirin NSAIDs when nondysplastic Barrett’s oesophagus cases were compared with population controls (OR = 0.69, 95% CI 0.49–0.97), the effect was weaker and nonsignificant when cases were compared with inflammation controls (OR = 0.82, 95% CI 0.57–1.18), and no dose-response effects were present in either analysis. We found no evidence that aspirin or non-aspirin NSAID use conferred risk reductions for dysplastic Barrett’s oesophagus, regardless of the control series. We excluded effect modification by known risk factors as an explanation for these null findings. Conclusions We found little support for an inverse association between use of NSAIDs and Barrett’s oesophagus. The question of whether or not these medications prevent the onset of Barrett’s oesophagus remains open.

Infection with Helicobacter pylori is associated with significantly reduced risks of oesophageal adenocarcinoma; however, few studies have examined the association between H. pylori and Barrett's oesophagus (BO), the precursor lesion. We explored the relationship between H. pylori infection and BO and sought to identify potential modifiers. We compared the prevalence of positive H. pylori serology among 217 adults with simple BO (without dysplasia), 95 with dysplastic BO and 398 population controls sourced from the metropolitan Brisbane area. We determined H. pylori serostatus using enzyme-linked immunosorbent assay. To estimate relative risks, we calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression in the entire sample and stratified by factors known to cause BO. The prevalence of H. pylori seropositivity was 12%, 3%, and 18%, respectively, among patients with simple BO, dysplastic BO and population controls. BO patients were significantly less likely to have antibodies for H. pylori (Simple BO: OR = 0.51, 95% CI: 0.30-0.86; Dysplastic BO: OR = 0.10, 95% CI: 0.03-0.33) than population controls. For simple BO, the association was diminished after adjustment for frequency of gastro-oesophageal reflux (GOR) symptoms. Adjustment for frequency of GOR symptoms did not substantially alter the observed effect for dysplastic BO. Although there was some variation in the magnitude of risk estimates across strata of age, sex, GOR symptoms and use of proton pump inhibitors or H2-receptor antagonists, the differences were uniformly nonsignificant. Helicobacter pylori infection is inversely associated with BO, and our findings suggest that decreased acid load is not the only mechanism underlying the H. pylori protective effect.

Background and Aim: To estimate the sero-prevalence of Helicobacter Pylori infection in the Australian adult population and identify determinants.

Obesity, gastroesophageal reflux, and smoking have repeatedly been shown to be important and independent risk factors for adenocarcinoma of the esophagus (EAC) and of the gastroesophageal junction (GEJAC). There have been few attempts, however, to quantify the proportion of disease associated with these potentially modifiable factors. The authors have estimated the population attributable fraction of EAC and GEJAC attributable to obesity, symptoms of gastroesophageal reflux, and smoking using data from a population-based case-control study conducted in Australia between 2002 and 2005. Cases were patients with EAC (n = 364) or GEJAC (n = 425). Controls (n = 1,580) were randomly sampled froma population register. Combinations of smoking, body mass index (weight in kilograms divided by height in meters squared), and gastroesophageal reflux together accounted for 76% (95% confidence interval: 66, 84) of EAC cases and 69% (95% confidence interval: 58, 78) of GEJAC cases. Individually, high body mass index (>= 30) and frequent acid reflux (>= 1 time/week) accounted for the greatest proportions of EAC (23% and 36%, respectively), and smoking and frequent symptoms of acid reflux accounted for the greatest proportions of GEJAC (43% and 28%, respectively). The present study suggests that these cancers may be largely prevented by maintaining healthy body mass index, avoiding smoking, and controlling symptomatic gastroesophageal reflux.

Background: It is currently unclear whether betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Methods: Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the community-based Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age- and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. Results: SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR = 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Conclusions: Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. Impact: This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case–control studies. Cancer Epidemiol Biomarkers Prev; 20(6); 1171–7. ©2011 AACR.

Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

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.We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's 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.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; andor =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.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.

Although sun exposure is known to be associated with basal cell carcinoma (BCC), it is not known what determines multiple occurrences of BCCs among sporadically affected individuals or why BCCs develop on uncommonly sun-exposed body sites like the trunk. In a prospective community-based skin cancer study in Queensland, Australia, we studied all participants who experienced a histologically confirmed BCC from 1992 to 2007. Sun exposure history was monitored, and dermatologists documented phenotype at baseline and signs of photodamage over the study period. Anatomic sites of all incident BCCs were recorded. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression. Of 401 participants who developed a new BCC during the 16 years of follow-up, 232 (58%) developed more than 1. Male sex (OR = 2.5, 95% CI 1.5-5.3) and age 60 or over (OR = 4.2, 95% CI 1.5-11.8) but not skin type were associated with highest BCC counts among those affected. Participants with high numbers of solar keratoses were most likely to experience the highest BCC counts overall (OR = 4.3, 95% CI 1.4-13.5). Moreover, occurrences of BCC on the trunk (OR = 3.3, 95% CI 1.4-7.6) and on the limbs (OR = 3.7, 95% CI 2.0-7.0) were strongly associated with high numbers of solar keratoses on these sites, respectively. Among those newly affected by BCC, chronic cutaneous sun damage predicts those who will be affected by more than 1 BCC, while chronic sun damage on the trunk and limbs predicts BCC occurrence on the trunk and limbs, respectively.

Medical out-of-pocket costs paid by patients can be problematic when it adversely affects access to care. Survey research involving patients with out-of-pocket expenses may have selection biases, so accurate estimates are unknown. During 2010–11, 419 participants from the QSkin Sun and Health Study (n=43794) had a confirmed diagnosis of either melanoma, prostate, breast, colorectal or lung cancer. These were matched to a general population group (n=421) and a group of high users of GP services (n=419). Medical fees charged and out-of-pocket medical expenses for Medicare services were analysed. Over 2 years, three-quarters of individuals with cancer paid up-front provider fees of up to A$20551 compared with A$10995 for the high GP user group and A$6394 for the general population group. Out-of-pocket expenses were significantly higher for those with cancer (mean A$3514) compared with the high GP-user group (mean A$1837) and general population group (A$1245). Highest expenses were for therapeutic procedures (mean A$2062). Older individuals, those with poor perceived health or private health insurance had the highest costs. Regardless of private insurance status, patients with one of the main five cancers pay significantly higher out-of-pocket costs for health care compared with those without cancer.

OBJECTIVE: Participation rates have been declining in case-control studies, particularly among controls, raising concerns about possible bias. Formal assessments of the effect of low participation on odds ratios (OR) are seldom presented however. We sought to quantify possible bias using multiple imputation techniques. METHODS: Using data from two Australian case-control studies, we estimated the relative risks of oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC), and serous ovarian cancer (SOC) associated with smoking and body mass index (BMI). We compared ORs observed using self-reported data from participating controls with ORs derived using imputed exposures for non-participating controls. RESULTS: Participating controls were less likely than non-participants to smoke currently. Smoking remained significantly associated with oesophageal cancer even under the most extreme assumption of smoking prevalence among non-participants (OSCC: observed OR 6.54, 4.62-9.28, imputed OR 3.94, 2.83-5.49; OAC: observed OR 2.69, 1.87-3.85 imputed OR 1.58, 1.13-2.22). For SOC however, risks associated with smoking were attenuated to null under plausible smoking assumptions among non-participants. BMI distributions were similar among participating and non-participating controls, and risk estimates were essentially unchanged. CONCLUSION AND IMPLICATIONS: Bias is not an inevitable consequence of low control participation and depends on the association examined. Sensitivity analyses can assist in interpretation of results.

Since hyperinsulinaemia may promote obesity-linked cancers, we compared type 2 diabetes prevalence among oesophageal adenocarcinoma (OAC) patients and population controls. Diabetes increased the risk of OAC (adjusted odds ratio 1.59, 95% confidence interval (CI) 1.04-2.43), although the risk was attenuated after further adjusting for body mass index (1.32, 95% CI 0.85-2.05).

Smoking has been identified as a risk factor for esophageal cancer; however, there is evidence that magnitudes and patterns of association differ by histologic type. The authors aimed to measure and compare the independent effects of various dimensions of smoking (duration, intensity, total dose, and time since quitting) on risks of esophageal adenocarcinoma (EAC), gastroesophageal junction adenocarcinoma (GEJAC), and esophageal squamous cell carcinoma (ESCC). They used data from a population-based Australian case-control study (2002-2005) comprising 367 EAC cases, 426 GEJAC cases, and 309 ESCC cases and 1,580 controls. Multivariate logistic and generalized additive logistic regression (for nonlinear dose effects) were used. Ever smokers had significantly higher risks of EAC (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.3, 2.3), GEJAC (OR = 2.4, 95% CI: 1.8, 3.2), and ESCC (OR = 2.8, 95% CI: 2.0, 4.0) than did never smokers; however, there were significant differences in magnitude and patterns of association between subtypes. When multiple dimensions of smoking were assessed concurrently, duration was significantly associated with all three subtypes but intensity was associated only with GEJAC and ESCC, and the associations were nonlinear. For all types of esophageal cancer, time since quitting was independently associated with approximately 15-19% risk reductions per decade.

Microsatellite instability (MSI) is an alternative pathway of colorectal carcinogenesis. It is found in 10% to 15% of sporadic colorectal neoplasms and is characterized by failure of the DNA mismatch-repair system. High-level MSI (MSI-H) is associated with tumor-infiltrating lymphocytes (TILs) and a favorable prognosis. Expression of Fas ligand (FasL/CD95L) by cancer cells may mediate tumor immune privilege by inducing apoptosis of antitumor immune cells. The aim of this study was to investigate the relationship between FasL expression and MSI status in primary colon tumors. Using immunohistochemistry, we detected FasL expression in 91 colorectal carcinoma specimens, previously classified according to the level of MSI as MSI-H (n = 26), MSI-low (MSI-L) (n = 29), and microsatellite stable (n = 36). Tumor-infiltrating lymphocyte density was quantified by immunohistochemical staining for CD3. MSI-H tumors were significantly associated with reduced frequency (P = .04) and intensity (P = .066) of FasL expression relative to non-MSI-H (ie, microsatellite stable and MSI-L) tumors. Higher FasL staining intensity correlated with reduced TIL density (P = .059). Together, these findings suggest that the abundance of TILs found in MSI-H tumors may be due to the failure of these tumor cells to up-regulate FasL and may explain, in part, the improved prognosis associated with these tumors.

Aspirin may reduce the risk of cancer at some sites but its effect at the lung is unclear. We prospectively examined associations between aspirin use and risk of lung cancer in 109,348 women in the Nurses' Health study from 1980 to 2004. During this time, 1,360 lung cancers were documented in participants 36-82 years of age. Aspirin use and smoking were assessed every 2 years. Risk of lung cancer was a non-significant 16% lower for regular aspirin users of one or two tablets per week and a significant 55% higher for users of 15 or more tablets per week compared with women who never regularly used aspirin. Results were similar when limited to never smokers. For both the low and high quantity aspirin users, risk of lung cancer did not decline or increase with longer durations of use, and associations attenuated as the latency period between aspirin assessment and lung cancer diagnosis was lengthened. Our findings, together with those from previous clinical trials and prospective studies, do not provide consistent evidence that aspirin influences the development of lung cancer and further investigation is required with adjustment for smoking.

Background and Objective Basal cell carcinoma (BCC) is the most common of all cancers. Ultraviolet radiation is the major etiologic agent in the pathogenesis of BCC, but there is not a straightforward relationship between cumulative exposure and risk. A high proportion of lesions arise on the trunk, which is generally much less exposed to the sun than the head, the major site affected. We tested the hypothesis that the phenotypic determinants and patterns of sun exposure that give rise to BCC on the head and trunk vary in a way that explains the anomalous site distribution. Methods The study was set in the context of the Nambour Skin Cancer Study, a community-based follow-up study among 1621 participants with virtually complete ascertainment of BCCs between 1992 and 2004. We compared phenotypic and sun exposure characteristics of participants who developed a first BCC of the head or trunk with those of participants who had no diagnosis of BCC. Results BCCs of the trunk were more likely to occur in men; they also occurred at a younger age than BCCs of the head. There was a positive association between sun sensitivity and BCC of the head that was absent for BCC of the trunk. A high number of solar keratoses conferred a greater than 3-fold risk for BCCs of both the head and the trunk. BCCs of the trunk had a particularly strong association with the number of reported sunburns and solar lentigines on the trunk, whereas many lentigines conferred a greater than 3-fold risk of truncal BCC compared with a 50% increased risk of BCC of the head. Limitations The relatively small numbers of tumors may have limited our ability to detect statistically significant differences. Conclusions BCCs of the trunk are the result of overexposure of the sensitive basal cells of the epidermis to ultraviolet radiation. This may result from acute intense exposures sufficient to cause sunburn among people whose ability to tan makes the skin of their face generally less susceptible to the carcinogenic effects of ultraviolet radiation.

Background Evidence for an association between aspirin or other nonsteroidal antiinflammatory drug (NSAID) use and basal cell carcinoma (BCC) has been inconsistent. Objective We conducted a systematic review and metaanalysis to assess the effect of oral NSAIDs on BCC. Methods PubMed, Web of Science, and Embase databases were searched up to December 3, 2014. A random effects model metaanalysis was used to calculate summary estimates of the effects of aspirin, nonaspirin NSAIDs, or any (aspirin or nonaspirin) NSAID use in patients with BCC. Results The summary estimates from 11 studies (1 randomized controlled trial, 5 cohort studies, and 5 case control studies) found a 10% risk reduction of BCC among those using any NSAID (relative risk [RR], 0.90 [95% confidence interval {CI}, 0.84-0.97]). A similar but not statistically significant inverse association was observed for nonaspirin NSAIDs (RR, 0.93 [95% CI, 0.86-1.02]), while aspirin use was more weakly associated (RR, 0.95 [95% CI, 0.91-1.00]). The strongest inverse associations were noted among those with either a history of skin cancers or a high prevalence of actinic keratoses. Limitations Dose-effect estimates could not be calculated because the available data were too heterogeneous to pool. Conclusion The intake of NSAIDs may help prevent BCC, particularly in high-risk populations. A large randomized controlled trial is required to confirm these findings.

Regular physical activity is important for optimal health and significant benefits occur from even modest amounts of physical activity,1 including lower cancer rates.2 There is consistent evidence from a systematic review and meta-analysis of cohort studies that physical activity is associated with a reduced risk of colon cancer.3 Research has also consistently demonstrated links between physical activity and reduced risk of post-menopausal breast cancer4 and endometrial cancer.5 The World Cancer Research Fund (WCRF) has concluded that there is “convincing” or “probable” evidence that insufficient physical activity causes cancers of the colon, post-menopausal breast and endometrium.6 The most recent Australian guidelines for physical activity and sedentary behaviour were released in February 2014.7 They recommend that adults perform at least 150 minutes of moderate intensity physical activity or 75 minutes of vigorous intensity physical activity per week to help improve blood pressure, cholesterol, heart health and muscle and bone strength. This should be increased to 300 minutes of moderate intensity physical activity or 150 minutes of vigorous intensity physical activity per week to reap greater health benefits and help to prevent cancer and unhealthy weight gain.7 The National Guidelines defines 60 minutes of moderate intensity physical activity on most days of the week (assumed 5 days) as a sufficient level to help prevent cancer. We aimed to estimate the fraction and number of cancers of the colon, post-menopausal breast and endometrium arising in the Australian population in 2010 that were attributable to failing to meet this target. We assumed that lower levels of physical activity conferred some benefit, but less than optimum.

Assays to determine the pathogenicity of unclassified sequence variants in disease-associated genes include the analysis of lymphoblastoid cell lines (LCLs). We assessed the ability of several assays of LCLs to distinguish carriers of germline BRCA1 and BRCA2 gene mutations from mutation-negative controls to determine their utility for use in a diagnostic setting.Post-ionising radiation cell viability and micronucleus formation, and telomere length were assayed in LCLs carrying BRCA1 or BRCA2 mutations, and in unaffected mutation-negative controls.Post-irradiation cell viability and micronucleus induction assays of LCLs from individuals carrying pathogenic BRCA1 mutations, unclassified BRCA1 sequence variants or wildtype BRCA1 sequence showed significant phenotypic heterogeneity within each group. Responses were not consistent with predicted functional consequences of known pathogenic or normal sequences. Telomere length was also highly heterogeneous within groups of LCLs carrying pathogenic BRCA1 or BRCA2 mutations, and normal BRCA1 sequences, and was not predictive of mutation status.Given the significant degree of phenotypic heterogeneity of LCLs after gamma-irradiation, and the lack of association with BRCA1 or BRCA2 mutation status, we conclude that the assays evaluated in this study should not be used as a means of differentiating pathogenic and non-pathogenic sequence variants for clinical application. We suggest that a range of normal controls must be included in any functional assays of LCLs to ensure that any observed differences between samples reflect the genotype under investigation rather than generic inter-individual variation.

Background Although animal studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, may protect against cutaneous squamous cell carcinoma (SCC) and actinic keratoses (AKs), possible effects on keratinocytic cancers in humans are unknown. Objective We sought to examine the relationship between ingestion of NSAIDs and the risk of SCC and AKs in humans. Methods We conducted a case-control study nested within a community-based cohort of 1621 people in southern Queensland, Australia. Eighty-six persons with SCC were compared with 187 age- and sex-matched control subjects randomly selected from within the cohort. NSAID use was captured through face-to-face interviews with study participants, supplemented by color photographs of product packaging. We defined regular use of NSAIDs as consumption of at least two tablets per week (low frequency) or at least 8 tablets per week (high frequency) for at least 1 year. AKs were counted on the face, ears, right hand, and right forearm by a single physician. Results Patients with SCC were significantly less likely than control subjects to have used any NSAIDs 8 or more times per week for more than 1 year (multivariate odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.71) and to have used full-dose NSAIDs 2 or more times per week for more than 5 years (OR, 0.20; 95% CI, 0.04-0. 96). Among participants without SCC, current regular users of NSAIDs (≥2 times per week) had significantly lower counts of AKs than nonusers (rate ratio [RR], 0.52; 95% CI, 0.30-0.91). Limitations Estimates of NSAID use were based on self-reported data. Statistical power to detect associations was limited by the number of cases with SCC. Conclusion Regular users of NSAIDs appear to have lower risks of SCC and lower counts of AKs than nonusers.

Appendicectomy and smoking are environmental factors that are known to influence ulcerative colitis (UC). The phenotype of UC is different in patients with coexistent primary sclerosing cholangitis (PSC). This study investigates the interaction of appendicectomy and PSC on the epidemiology and clinical behaviour of colitis.Patients were from the Brisbane IBD Research Group database. Controls were from the Australian twin registry. Seventy eight PSC-inflammatory bowel disease (PSC-IBD) patients, 12 pure PSC, and 294 UC patients were matched with 1466 controls by sex and birth cohort that comprised randomly selected twins from each twin pair. The effects of appendicectomy, smoking, or PSC on the onset of disease, disease extent, disease severity (as identified by immunosuppression-colectomy or liver transplant), and disease related complications (high grade dysplasia, colorectal cancer, or cholangiocarcinoma) were investigated using univariate and multiple logistic regression analyses.PSC-IBD patients had a more extensive colitis than UC patients (p0.0001) but required less immunosuppression (p = 0.007), which was independent of disease extent. They were more likely to have high grade dysplasia or colorectal cancer (p = 0.029) than UC patients. Appendicectomy rates in the PSC groups were not different from the control groups (p = 0.72, 0.76), which was in sharp contrast with UC where the rate was four times less (p = 0.0001). Prior appendicectomy appeared to be associated with an approximate five year delay in the onset of intestinal (PSC-IBD or UC) or hepatic (PSC) disease, which was independent of smoking. Appendicectomy did not independently alter the extent or severity of disease in PSC. In contrast, prior appendicectomy in UC was associated with more extensive disease but with a lesser requirement for immunosuppression or colectomy for the treatment of colitis (p = 0.004). There were trends for high grade dysplasia or colorectal cancer with appendicectomy in both PSC-IBD and UC. Although these trends were not statistically significant, colorectal cancer appeared more frequent with appendicectomy in a meta-analysis of the available UC data from this and another Australian study.In contradistinction to UC, appendicectomy did not significantly influence the prevalence of the PSC groups, or the extent of colitis in PSC-IBD, but as with UC, did appear to delay their onset. The extensive milder colitis, which is characteristic of PSC-IBD, relates to other poorly understood factors. Further prospective studies are required to determine any influence of appendicectomy on the extent of colitis in IBD and an associated dysplasia or colorectal cancer.

The research project described in the present paper aimed to explore the types of self-reported management which families in relatively 'high', 'moderate' and 'low' medically resourced areas use for episodes of incapacity and the length of time from an initial symptom to the management behaviours. A telephone survey was conducted in rural and remote Queensland, Australia, to explore one or more types of management for the most recent incapacity episode of family members. A respondent indicated at least one type of management for any one episode. These included using a home remedy, self-treatment and an ambulatory doctor's visit. Data were analysed descriptively and analytically. Log transformations were used for all outcomes prior to using bivariate analyses which incorporated the correlation between observations to compare the time from initial symptom to management between groups. Among 394 households contacted, 270 provided information about 697 household members, 269 (38.5%) of whom had had at least one episode of incapacity in the previous 12 months. Among people in each of the three resourced areas, there was a significant difference in the length of time taken to visit accident and emergency (A&E) units. Men visited the units and consulted books earlier than women. Although age was not quite significantly related to the use of A&E units (P = 0.06), data suggested that people 35 years or older tended to take a longer time to use the services than the younger age groups. After taking into account that the members of the same household might take the same time from initial symptoms to management, people who were incapacitated and lived in areas with different levels of medical resources and gender were likely to be different in the time taken to use services at the A&E units.

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Background: Increased levels of tumor necrosis factor (TNF)-alpha and oxidative stress have been implicated as factors contributing to hepatic injury in fatty liver diseases. As steatosis is associated with an accelerated progression of fibrosis in chronic hepatitis C (HCV), we hypothesized that the messenger (m)RNA expression of genes involved with the production of reactive oxygen species, inflammation and cellular injury would be increased in liver tissue from subjects with steatosis and chronic HCV. Methods: Real-time polymerase chain reaction was performed to determine relative mRNA expression levels of collagen I, TNF-alpha, cytochrome P450 2E1 (CYP 2E1), transforming growth factor-beta1 and CD14 in liver biopsies from 38 patients with chronic HCV. The mRNA expression levels were compared between subjects with and without steatosis, fibrosis, and inflammation. Results: Multivariate analysis demonstrated that collagen I mRNA expression was increased by 199% in steatosis (P = 0.02), 85% in moderate to severe fibrosis (P = 0.02) and 157% in inflammation (P = 0.03). Livers of patients with steatosis also had an increase in TNF-alpha mRNA expression by 50% (P = 0.03) and CYP 2E1 expression by 37% (P = 0.04) compared with non-steatotic livers. Tumor necrosis factor-alpha protein was localized to Kupffer cells, bile ducts and portal inflammatory cells by immunohistochemistry. Conclusion: Increased expression of TNF-alpha may be involved in the pathogenesis of liver injury and progression of fibrosis in individuals who have steatosis in association with chronic HCV. (C) 2003 Blackwell Publishing Asia Pty Ltd.

At semiarid Charters Towers, north Queensland, Australia, the importance of Aedes aegypti (L.) in wells was assessed in relation to the colonization of surface habitats during the wet season. From April to July 1999, 10 wells (five positive for Ae. aegypti) were monitored to assess their status and larvae population numbers therein. All surface containers located within a 100 m radius of each well were removed, treated with s-methoprene or sealed to prevent the utilization of these containers by mosquitoes. These inner cores were surrounded by outer zones for a further 100 m in which surface containers were left untreated but all subterranean habitats were treated. Ovitraps were monitored monthly in the inner cores for 36 wk from August 1999 to April 2000 and differences in the proportions of ovitraps positive for Ae. aegypti and Ochlerotatus notoscriptus (Skuse) were analyzed by logistic regression. Analysis of the proportions of ovitraps positive for Ae. aegypti near positive wells indicated significantly greater colonization from November to March (the wet season), compared with those situated near Ae. aegypti negative wells. As Oc. notoscriptus were not produced from subterranean sites, comparisons of the proportions of ovitraps positive for Oc. notoscriptus in positive and negative inner cores provided an indication of the relative productivity of the uncontrolled surface containers in the outer zones. Differences in the utililization of ovitraps by Oc. notoscriptus among positive and negative cores were observed during only one month (March), when oviposition was greater in ovitraps in the negative cores, compared with the positive cores. Best subsets linear regression analysis of the proportion of ovitraps positive for Ae. aegypti against meteorological variables (rainfall, mean wind speed, mean relative humidity, mean minimum, and maximum temperature) during the week of ovitrapping indicated that minimum temperature and wind speed accounted for 63.4% of the variability. This study confirms that for semiarid towns such as Charters Towers, the practice of treating a relatively small number of key subterranean habitats during winter will significantly affect Ae. aegypti recolonization of surface container habitats during summer, the period of greatest risk for dengue.

Introduction: Premature menopause and early menopause are known risk factors for adverse health outcomes in later life. While cigarette smoking is an established risk factor for earlier age at menopause, the overall size and strength of its relationship with premature or early menopause is yet to be fully elucidated.Objectives: To quantify the magnitude of the relationship between cigarette smoking status with the age at final menstrual period (FMP).Methods: The International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) enables the use of pooled data on 51 450 women from nine longitudinal observational studies in the UK, Scandinavia, Australia and Japan. Age at FMP was confirmed by at least 12 months of cessation of menses and categorised as: premature menopause (FMP before age 40), early menopause (FMP 40–44 years), 45–49 years, 50–51 years, 52–53 years, or 54 or more years. Cigarette smoking was categorised as current smoker, past smoker, or never smoker. Multinomial logistic regression was used to identify associations with age categories for FMP, after adjusting for birth year, age at menarche, education level, marital status, parity, and body mass index during midlife.Findings: Overall 18% of the women were smokers, with a mean age at FMP of 48.9 years (SD 4.2). The mean (SD) for never or past smokers was 50.1 (4.2) years. Current smokers were at a higher risk of having premature menopause (RRR 1.48, 95% CI 1.17 to 1.88), early menopause (1.70, 1.43 to 2.03), FMP at 45–49 years (1.43, 1.31 to 1.56) compared with never smokers. Past smokers had similar risks as never smokers.Conclusions: This study identified robust evidence for the effect of cigarette smoking on the timing of menopause before the age of 50, with the effect being highest for early menopause. Findings underscore support for smoking prevention and quitting programmes for women of reproductive age.

Nonsteroidal anti-inflammatory drugs (NSAIDS) have received increasing attention as potential chemopreventive agents of skin cancer, but evidence is inconsistent. To investigate whether the use of aspirin and other NSAIDS reduces the risk of squamous cell carcinoma (SCC), we conducted a systematic review on the basis of published epidemiologic studies and calculated summary estimates for aspirin, nonaspirin NSAIDS, and any NSAIDS use. Summary estimates from nine studies (five case–control, three cohort, and one intervention) indicated significantly reduced risks of SCC among users of nonaspirin NSAIDS (relative risk (RR) 0.85, 95% confidence interval (CI) 0.78–0.94) and among users of any NSAIDS (RR 0.82, 95% CI 0.71–0.94) compared with nonusers with the effect seen particularly in those with previous actinic skin tumors. A reduced risk was also observed among aspirin users, although with borderline statistical significance (RR 0.88 95% CI 0.75–1.03). There was significant heterogeneity between studies regarding SCC risk estimates for aspirin use and any NSAIDS use. These findings suggest that NSAIDS collectively have the potential to prevent the development of cutaneous SCC.

Background: Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Methods: Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Results: Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of

Cutaneous melanomas are postulated to arise through at least two causal pathways, namely the "chronic sun exposure" and "nevus" pathways. While chronic sun exposure probably causes many head/neck melanomas, its role at other sites is unclear. In a population-based, case-case comparison study conducted in Brisbane, Australia, we determined the prevalence and epidemiologic correlates of chronic solar damage in skin adjacent to invasive, incident melanomas on the trunk (n = 418) or head/neck (n = 92) among patients aged 18-79 in 2007-2010. Participants self-reported information about environmental and phenotypic factors, and a dermatologist counted nevi and actinic keratoses. Dermatopathologists assessed solar elastosis adjacent to each melanoma using a four-point scale (nil, mild, moderate, marked), and noted the presence or absence of adjacent neval remnants. We measured associations between various factors and solar elastosis using polytomous logistic regression. Marked or moderate solar elastosis was observed in 10% and 27%, respectively, of trunk melanomas, and 60% and 17%, respectively, of head/neck melanomas. At both sites, marked elastosis was positively associated with age (p(trend) 0.0001) and inversely associated with neval remnants (p(trend) 0.001). For trunk melanomas, marked elastosis was associated with highest quartiles of total sun exposure [odds-ratio (OR) = 5.47, 95% confidence interval (CI) = 1.08-27.60] and facial freckling (OR = 2.98, 95% CI = 1.17-7.56), and inversely associated with deeply tanning skin (OR = 0.29, 95% CI = 0.08-1.11) and high nevus counts (OR = 0.08, 95% CI = 0.01-0.66). Mostly similar associations were observed with moderate solar elastosis. About one in three trunk melanomas in Queensland have evidence of moderate-to-marked sun damage, and they differ in risk associations from those without.

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.

Naevi may change in size, shape and colour due to multiple inherent and external factors. We observed naevi changing size in adults at high risk of melanoma, and assessed associations of change with demographic factors, skin type, sites of naevi and history of melanoma.In total, 29 participants with a personal or first-degree family history of melanoma or those deemed at high risk with multiple naevi of variable morphologies had all melanocytic naevi 0.5-1 cm imaged and their maximum diameter recorded. Maximum diameters from repeat imaging of naevi 12 months later were compared to baseline measurements. Newly appearing naevi ≥5 mm and naevi that grew or decreased in size by 20% or more were defined as changeable naevi. Associations between changeable naevi and participants' age, sex, skin type, body sites of naevi and personal and family history of melanoma were assessed.There was no difference in changeable naevus rates among sex, age or skin type. Among the body sites, the head and neck were most likely to have changeable naevi, and the upper limbs the least likely. A family history of melanoma almost tripled the likelihood of having changeable naevi compared with those without both personal and family melanoma history.Naevi can continue to change in size throughout adulthood, showing both increases and decreases in size as well as the appearance of new naevi. This has important clinical implications, in particular for sequential body imaging used for the detection of melanoma.

Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-beta, interleukin-10, and tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P =.001), immune-mediated liver disease (P =.018), normal pre-OLT creatinine clearance (P =.037), and fewer HLA class 1 mismatches (P =.038) were independently associated with rejection, Renal impairment occurred in 80% of patients and was moderate or severe in 39%, Clinical variables independently associated with renal impairment were female sex (P =.001), pre-OLT renal dysfunction (P =.0001), and a diagnosis of viral hepatitis (P =.0008), There was a significant difference in the frequency of TNF-alpha -308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-alpha -308 polymorphism and graft rejection approached significance (P =.06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT, Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions.

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/m 2 ) or extensive (29.6±5.9 kg/m 2 ) subsinusoidal fibrosis than in those patients with no subsinusoidal fibrosis (25.5±3.7 kg/m 2 ). The extent of α -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.

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)