Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations.

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

Thirteen cancers associated with HIV infection in a Black South African cancer patient population (1995-2016).

South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995-2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case-control associations between specific cancers and HIV, using participants with non-infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (ORadj ; 95%CI): (99.1;72.6-135.1), non-Hodgkin lymphoma (11.3;9.3-13.6), cervical cancer (2.7;2.4-3.0), Hodgkin lymphoma (3.1;2.4-4.2), cancer of the eye/conjunctiva (18.7;10.1-34.7), anogenital cancers (anus [2.1;1.4-3.2], penis [5.4;2.7-10.5], vulva [4.8;3.5-6.4], vagina [5.5;3.0-10.2]), oropharyngeal cancer (1.6;1.3-1.9), squamous cell carcinoma of the skin (3.5;2.4-4.9), melanoma (2.0;1.2-3.5) and cancer of the larynx (1.7;1.3-2.4). Kaposi's sarcoma odds ratios increased from the pre-ART (1995-2004) to the early ART (2005-2009) period but declined in the late ART (2010-2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV-associated cancers found in other African settings. The odds ratios of conjunctival and HPV-related cancers continue to rise in the ART era as the HIV positive population ages.

Kaposi sarcoma-associated herpesvirus, HIV-1 and Kaposi sarcoma risk in black South Africans diagnosed with cancer during antiretroviral treatment rollout.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj ) and 95% confidence intervals (CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98%. Among 6649 controls, KSHV seropositivity was higher in males (ORadj  = 1.4 [95%CI 1.23-1.52]), in persons with HIV, (ORadj  = 4.2 [95%CI 3.74-4.73]) and lower in high school leavers (ORadj  = 0.7 [95%CI 0.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28% and 28%, Ptrend < .001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend < .001). HIV-1 seroprevalence increased from 10% in the pre-ART period to 22% in the late ART period (Ptrend < .001). Compared to HIV-1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI 11-62) in HIV-1 seronegative participants and an OR of 2501 (95%CI 1083-5776) in HIV-1 seropositive participants. HIV-1 increases the risk of KS in those infected with KSHV by 100-fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene.

Usefulness of high-risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer: A systematic review and meta-analysis.

We reviewed the literature on the importance of selected anti-high-risk human papillomavirus (HR-HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as potential serological markers for early detection of individuals at high risk of cervical cancer. We searched for studies in PubMed and Embase databases published from 2010 to 2020 on antibodies against HR-HPV E6 and E7 early proteins and cervical cancer. Pooled sensitivity and specificity for HPV16 and HPV18 antibodies were calculated using a bivariate hierarchical random-effects model. A total of 69 articles were identified; we included three studies with 1550 participants. For the three HPV16/18 E6 and E7 antibody tests, enzyme-linked immunosorbent assay-based assays had a sensitivity of 18% for detecting CIN2+ (95% confidence interval [CI]: 15-21) and a specificity of 96% (95% CI: 92-98), for slot-blot, sensitivity was 28.9% (95% CI: 23.3-35.1) and specificity was 72% (95% CI: 66.6-77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S-transferase, sensitivity was 16% (95% CI: 8.45-28.6) and specificity was 98% (95% CI: 97-99) for detecting invasive cervical cancer. HR-HPV16/18 E6 and E7 serological markers showed high specificity, but sensitivity was suboptimal for the detection of cervical cancer in either population screening settings or as point-of-care screening tests.

Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

[This corrects the article DOI: 10.1371/journal.pgen.1006866.].

Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

HLA and KIR Associations of Cervical Neoplasia.

Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods: Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent. Results: The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.

Physical activity, obesity and sedentary behaviour and the risks of colon and rectal cancers in the 45 and up study.

BACKGROUND: Obesity and physical activity (PA) are predictors of colon (CC) and rectal (RC) cancers. Prolonged sitting is also emerging as a potential predictor for these cancers. Little knowledge exists about the interactive effects of obesity, PA and prolonged sitting on cancer risk. This analysis assessed independent and interactive effects of PA, body mass index (BMI) and sitting time on CC and RC risks. METHODS: This analysis used data from a prospective study of 226,584 participants aged 45 years and over in New South Wales (NSW), Australia, who joined the 45 and Up study between 2006 and 2009. Baseline data were linked with data relating to mortality, cancer registration, hospital admission and Department of Human Services to December 2010. Multivariable Cox regression was used to estimate adjusted hazard ratios (referred to as relative risks, RRs) and 95% confidence intervals (Cis). Statistical significance was defined as p < 0.05. RESULTS: There were 846 and 369 ascertained cases of CC and RC. BMI was positively associated with CC risk (p = 0.003, P-trend = 0.0006) but not with RC. CC risk was increased in participants in the highest BMI quartile (≥29.4-≤50 kg/m2) compared to the lowest (15- < 23.6 kg/m2), (RR = 1.32, 95% CI:1.08-1.63). PA was associated with CC risk (p = 0.02) but not with RC. Specifically, CC risk was lower in individuals partaking in any amount of vigorous activity (time/week) compared to participants with no engagement (RR = 0.78, 95% CI:0.65-0.93). Sitting time was not associated with CC or RC. We found no evidence of interactive effects of PA, BMI and prolonged sitting on cancer risk. CONCLUSION: This evidence suggests that a healthy weight and vigorous activity are essential to reduce CC risk since these factors may be independent of each other.

Adult body size, sexual history and adolescent sexual development, may predict risk of developing prostate cancer: Results from the New South Wales Lifestyle and Evaluation of Risk Study (CLEAR).

Prostate cancer (PC) is the most common non-cutaneous cancer in men worldwide. The relationships between PC and possible risk factors for PC cases (n = 1,181) and male controls (n = 875) from the New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) were examined in this study. The associations between PC risk and paternal history of PC, body mass index (BMI), medical conditions, sexual behaviour, balding pattern and puberty, after adjusting for age, income, region of birth, place of residence, and PSA testing, were examined. Adjusted risk of PC was higher for men with a paternal history of PC (OR = 2.31; 95%CI: 1.70-3.14), personal history of prostatitis (OR = 2.30; 95%CI: 1.44-3.70), benign prostatic hyperplasia (OR = 2.29; 95%CI: 1.79-2.93), being overweight (vs. normal; OR = 1.24; 95%CI: 0.99-1.55) or obese (vs. normal; OR = 1.44; 95%CI: 1.09-1.89), having reported more than seven sexual partners in a lifetime (vs. < 3 partners; OR = 2.00; 95%CI: 1.49-2.68), and having reported more than 5 orgasms a month prior to PC diagnosis (vs. ≤3 orgasms; OR = 1.59; 95%CI: 1.18-2.15). PC risk was lower for men whose timing of puberty was later than their peers (vs. same as peers; OR = 0.75; 95%CI: 0.59-0.97), and a smaller risk reduction of was observed in men whose timing of puberty was earlier than their peers (vs. same as peers; OR = 0.85; 95%CI: 0.61-1.17). No associations were found between PC risk and vertex balding, erectile function, acne, circumcision, vasectomy, asthma or diabetes. These results support a role for adult body size, sexual activity, and adolescent sexual development in PC development.

Menopausal hormone therapy use and breast cancer risk in Australia: Findings from the New South Wales Cancer, Lifestyle and Evaluation of Risk study.

Randomised controlled trials and large-scale observational studies have found that current use of menopausal hormone therapy (MHT) is associated with an increased risk of breast cancer; this risk is higher for oestrogen-progestagen combination therapy than for oestrogen-only therapy. Our study was designed to estimate MHT-associated breast cancer risk in a population of Australian women. Data were analysed for postmenopausal women with self-reported incident invasive breast cancer (n = 1,236) and cancer-free controls (n = 862), recruited between 2006 and 2014 into a large case-control study for all cancer types, the NSW CLEAR study. Information on past and current MHT use was collected from all participants, along with other lifestyle and demographic factors, using a self-administered questionnaire. Unmatched multivariable logistic regression was performed, adjusting for socio-demographic, reproductive and health behaviour variables, body mass index and breast screening history. Compared to never users of MHT, the adjusted odds ratio (aOR) for breast cancer in current users of any type of MHT was 2.09 (95% CI: 1.57-2.78; p < 0.0001) and for past users of any type of MHT was 1.03 (0.82-1.28; p = 0.8243). For current users of oestrogen-only and oestrogen-progestagen therapy, aORs were 1.80 (1.21-2.68; p = 0.0039) and 2.62 (1.56-4.38; p = 0.0003), respectively. These findings are consistent with those from other international observational studies, that current, but not past, use of MHT is associated with a substantially increased risk of breast cancer.

Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis.

Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.

Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence.

BACKGROUND: The smoking epidemic in Australia is characterised by historic levels of prolonged smoking, heavy smoking, very high levels of long-term cessation, and low current smoking prevalence, with 13% of adults reporting that they smoked daily in 2013. Large-scale quantitative evidence on the relationship of tobacco smoking to mortality in Australia is not available despite the potential to provide independent international evidence about the contemporary risks of smoking. METHODS: This is a prospective study of 204,953 individuals aged ≥45 years sampled from the general population of New South Wales, Australia, who joined the 45 and Up Study from 2006-2009, with linked questionnaire, hospitalisation, and mortality data to mid-2012 and with no history of cancer (other than melanoma and non-melanoma skin cancer), heart disease, stroke, or thrombosis. Hazard ratios (described here as relative risks, RRs) for all-cause mortality among current and past smokers compared to never-smokers were estimated, adjusting for age, education, income, region of residence, alcohol, and body mass index. RESULTS: Overall, 5,593 deaths accrued during follow-up (874,120 person-years; mean: 4.26 years); 7.7% of participants were current smokers and 34.1% past smokers at baseline. Compared to never-smokers, the adjusted RR (95% CI) of mortality was 2.96 (2.69-3.25) in current smokers and was similar in men (2.82 (2.49-3.19)) and women (3.08 (2.63-3.60)) and according to birth cohort. Mortality RRs increased with increasing smoking intensity, with around two- and four-fold increases in mortality in current smokers of ≤14 (mean 10/day) and ≥25 cigarettes/day, respectively, compared to never-smokers. Among past smokers, mortality diminished gradually with increasing time since cessation and did not differ significantly from never-smokers in those quitting prior to age 45. Current smokers are estimated to die an average of 10 years earlier than non-smokers. CONCLUSIONS: In Australia, up to two-thirds of deaths in current smokers can be attributed to smoking. Cessation reduces mortality compared with continuing to smoke, with cessation earlier in life resulting in greater reductions.

Prevalence and correlates of current smoking among medical oncology outpatients.

BACKGROUND: Continued smoking following a cancer diagnosis has adverse impacts on cancer treatment and puts individuals at risk of secondary cancers. Data on the prevalence and correlates of smoking among cancer patients are critical for successfully targeting smoking cessation interventions. AIMS: To explore among a sample of medical oncology outpatients (a) the prevalence of self-reported current smoking and (b) the demographic and psychosocial factors associated with self-reported smoking. METHODS: A heterogeneous sample of cancer patients aged 18 years or over was recruited from 1 of 11 medical oncology treatment centres across Australia. Patients completed a survey assessing the following: smoking status; socio-demographic, disease and treatment characteristics; time since diagnosis; anxiety; and depression. Factors associated with self-reported smoking were examined using a univariate and multivariate mixed-effects logistic regression. RESULTS: A total of 1379 patients returned surveys and 1338 were included in the analysis. The prevalence of current smoking was 10.9% (n = 146). After adjusting for treatment centre, patients aged 65 years and older and those without health concession cards were significantly less likely to smoke. Patients diagnosed with lung cancer and those without private health insurance were more likely to smoke. DISCUSSION: A minority of cancer patients reported continued smoking at an average time of 13 months post-diagnosis. Patients, who are younger, have been diagnosed with lung cancer and have lower socioeconomic status are at-risk groups and represent important targets for smoking cessation advice and intervention. Copyright © 2015 John Wiley & Sons, Ltd.

Co-occurrence of chronic disease lifestyle risk factors in middle-aged and older immigrants: A cross-sectional analysis of 264,102 Australians.

BACKGROUND: The way in which lifestyle risk factors for chronic disease co-occur among people with different cultural backgrounds is largely unknown. METHODS: This study investigated chronic disease risk among immigrants aged ≥45 years in Australia by combining common lifestyle risk factors into a weighted chronic disease risk index (CDRI). Among 64,194 immigrants and 199,908 Australian-born participants in the 45 and Up Study (2006-2009), Poisson regression was used to derive relative risks (RR) and 95% confidence intervals (CI) for five risk factors (smoking, alcohol use, overweight/obesity, physical activity, diet) by place of birth adjusting for socio-demographic characteristics. Multiple linear regression was used to determine adjusted mean differences (AMDs) in CDRI score by place of birth and years lived in Australia. RESULTS: Immigrants had higher RRs of smoking than Australian-born participants, lower RRs of excessive alcohol consumption and overweight/obesity, and no difference in RR for physical inactivity and insufficient fruit/vegetable intake. Participants born in the Middle East/North Africa (AMD 3.5, 95% CI 2.7, 4.3), Eastern/Central Europe (1.3, 0.8, 1.9), and Western Europe (0.5, 0.1, 0.8) had higher mean CDRI scores than Australian-born participants, while participants born in East Asia (-7.2, -7.8, -6.6), Southeast Asia (-6.6, -7.2, -6.1), Central/South Asia (-3.1, -4.0, -2.1), Sub-Saharan Africa (-1.9, -2.6, -1.2) and the United Kingdom/Ireland (-0.2, -0.5, 0.0) had lower scores. CDRI score among immigrants generally approximated that of Australian-born participants with greater years lived in Australia. CONCLUSIONS: This study reveals differences in potential risk of chronic disease among different immigrant groups in Australia.

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma.

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.

Quantifying disparities in cancer incidence and mortality of Australian residents of New South Wales (NSW) by place of birth: an ecological study.

BACKGROUND: In 2013, about 32% of the Australian population over 15 years of age was born overseas. Previous cancer-related immigrant health studies identified differences in mortality and incidence between immigrants and Australian-born people. To identify groups that may require targeted interventions, we describe by region of birth: 1. the highest cancer incidence and mortality rates for NSW residents, Australia's most populous state; and 2. mortality to incidence ratios (MIR) for all cancers. METHODS: Cancer incidence and mortality data were obtained from NSW residents for 2004-2008 (averaged) by sex, region of birth and 10 year age groups. Age standardised incidence and mortality rates were calculated with 95% confidence intervals (per 100,000), using the world standard population. In the place of 5-year survival rates, we used age standardised MIRs (=M/I) as a simple proxy indicator of cancer survival. RESULTS: All-cancer incidence only exceeded Australian born people (308.5) for New Zealand born (322). The highest reported incidence rates for cancers from all regions were prostate and breast cancers. All-cancer mortality exceeded Australian-born (105.3) in people born in Western Europe (110.9), Oceania (108.2) and UK and Ireland (106.4). For Australian-born residents, the MIR was 34 cancer deaths per 100 cases compared to residents from Central Europe at 38 deaths per 100 cases and lowest at 28 deaths per 100 cases for residents from Central and Southern Asia. CONCLUSION: Some disparities between Australian-born NSW residents and immigrants were identified in prostate, breast and lung cancer mortality rates. While on average most immigrant groups have similar cancer characteristics for the top cancers, areas for improvement to inform strategies to alleviate cancer disparities are required. This analysis suggests that NSW residents could benefit from specific prevention programmes on healthy eating and smoking cessation, especially people from Central Europe, UK and Ireland and Western Europe. Rising immigration rates encourage us to continue to address the areas indicated for improvement.