Alcohol intake and endogenous sex hormones in women: meta-analysis of cohort studies and Mendelian randomization.

Background: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. Methods: We investigated cross-sectional associations between self-reported alcohol intake and serum or plasma concentrations of oestradiol, oestrone, progesterone (in pre-menopausal women only), testosterone, androstenedione, DHEAS (dehydroepiandrosterone sulphate) and SHBG (sex hormone binding globulin) in 45 431 pre-menopausal and 173 476 post-menopausal women. We performed multivariable linear regression separately for UK Biobank, EPIC (European Prospective Investigation into Cancer and Nutrition) and EHBCCG (Endogenous Hormones and Breast Cancer Collaborative Group), and meta-analysed the results. For testosterone and SHBG, we also conducted two-sample Mendelian Randomization (MR) and colocalisation using the ADH1B (Alcohol Dehydrogenase 1B) variant (rs1229984). Results: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in pre-menopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal oestradiol to 6.6% for post-menopausal DHEAS. There was an inverse association of alcohol with SHBG in post-menopausal women but a small positive association in pre-menopausal women. MR identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI: 0.6%, 7.6%) and free testosterone (7.8%; 4.1%, 11.5%), and an inverse association with SHBG (-8.1%; -11.3%, -4.9%). Colocalisation suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (PP4: 0.81 and 0.97 respectively). Conclusions: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.

Performance of cardiovascular disease risk prediction equations in more than 14 000 survivors of cancer in New Zealand primary care: a validation study.

BACKGROUND: People with cancer have an increased risk of cardiovascular disease. Risk prediction equations developed in New Zealand accurately predict 5-year cardiovascular disease risk in a general primary care population in the country. We assessed the performance of these equations for survivors of cancer in New Zealand. METHODS: For this validation study, patients aged 30-74 years from the PREDICT open cohort study, which was used to develop the New Zealand cardiovascular disease risk prediction equations, were included in the analysis if they had a primary diagnosis of invasive cancer at least 2 years before the date of the first cardiovascular disease risk assessment. The risk prediction equations are sex-specific and include the following predictors: age, ethnicity, socioeconomic deprivation index, family history of cardiovascular disease, smoking status, history of atrial fibrillation and diabetes, systolic blood pressure, total cholesterol to HDL cholesterol ratio, and preventive pharmacotherapy (blood-pressure-lowering, lipid-lowering, and antithrombotic drugs). Calibration was assessed by comparing the mean predicted 5-year cardiovascular disease risk, estimated using the risk prediction equations, with the observed risk across deciles of risk, for men and women, and according to the three clinical 5-year cardiovascular disease risk groups in New Zealand guidelines (<5%, 5% to <15%, and ≥15%). Discrimination was assessed by Harrell's C statistic. FINDINGS: 14 263 patients were included in the study. The mean age was 61 years (SD 9) for men and 60 years (SD 8) for women, with a median follow-up of 5·8 years for men and 5·7 years for women. The observed cardiovascular disease risk was underpredicted by a maximum of 2·5% in male and 3·2% in female decile groups. When patients were grouped according to clinical risk groups, observed cardiovascular disease risk was underpredicted by less than 2% in the lower risk groups and overpredicted by 2·2% for men and 3·3% for women in the highest risk group. Harrell's C statistics were 0·67 (SE 0·01) for men and 0·73 (0·01) for women. INTERPRETATION: The New Zealand cardiovascular disease risk prediction equations reasonably predicted the observed 5-year cardiovascular disease risk in survivors of cancer in the country, in whom risk prediction was considered clinically appropriate. Prediction could be improved by adding cancer-specific variables and considering competing risks. Our findings suggest that the equations are reasonable clinical tools for use in survivors of cancer in New Zealand. FUNDING: Auckland Medical Research Foundation, Health Research Council of New Zealand.

Bias in survival estimates created by a requirement for consent to enter a clinical breast cancer registry.

BACKGROUND: A requirement for consent for inclusion may bias the results from a clinical registry. This study gives a direct measure of this bias, based on a population-based clinical breast cancer registry where the requirement for consent was removed after further ethical review and data could be re-analysed. METHODS: In Auckland, New Zealand, the population-based clinical breast cancer registry required written patient consent for inclusion from 2000-2012. A subsequent ethical review removed this requirement and allowed an analysis of consented and non-consented patients. Kaplan-Meier survival to 10 years (mean follow-up 5.1 years, maximum 13.9 years), demographic and clinical characteristics were compared. Of 9244 women with invasive cancer, 926 (10.4%) were not consented, and of 1642 women with ductal carcinoma in situ, 245 (14.9%) were not consented. RESULTS: Survival was much higher for consenting patients; invasive cancer, 5 year survival 83.2% (95% confidence limits 82.2-84.1%) for consenting patients, 57.1% (53.0-60.9%) for non-consenting, and 80.8% in all patients. Analyses based only on consenting patients overestimate survival in all patients by around 2% at 2, 5, and 10 years. Non-consented patients were older, more often of Pacific ethnicity, had fewer screen-detected cancers, and more often had metastatic disease; they less frequently had primary surgery or systemic treatments. CONCLUSION: Data from a registry requiring active consent gives an upward bias in survival results, as non-consenting patients have more extensive disease, less treatment, and lower survival. To give unbiased results active consent should be not required in a clinical cancer registry.

Lung cancer mutation testing: a clinical retesting study of agreement between a real-time PCR and a mass spectrometry test.

To investigate the clinical validity and utility of tests for detecting Epidermal Growth Factor Receptor (EGFR) gene mutations in non-squamous non-small cell lung cancer patients, tumour DNA extracts from 532 patients previously tested by the cobas EGFR Mutation Test (RT-PCR test) were retested by the Sequenom/Agena Biosciences MassArray OncoFocus mass spectrometry test (MS test). Valid results from both tests were available from 470 patients (88%) for agreement analysis. Survival data were obtained for 513 patients (96%) and 77 patients (14%) were treated with EGFR tyrosine kinase inhibitors (TKIs). Agreement analysis revealed moderately high positive (79.8%), negative (96.9%) and overall percentage agreement (93.2%) for the detection of EGFR mutations. However, EGFR mutations were detected by one test and not by the other test in 32 patients (7%). Retesting of discordant samples revealed false-positive and false-negative results generated by both tests. Despite this, treatment and survival outcomes correlated with the results of the RT-PCR and MS tests. In conclusion, this study provides evidence of the clinical validity and utility of the RT-PCR and MS tests for detection of EGFR mutations that predict prognosis and benefit from EGFR-TKI treatment. However, their false-positive and false-negative test results may have important clinical consequences.

The role of multilevel factors in geographic differences in bicycle crash risk: a prospective cohort study.

BACKGROUND: Regular cycling plays an important role in increasing physical activity levels but raises safety concerns for many people. While cyclists bear a higher risk of injury than most other types of road users, the risk differs geographically. Auckland, New Zealand's largest urban region, has a higher injury risk than the rest of the country. This paper identified underlying factors at individual, neighbourhood and environmental levels and assessed their relative contribution to this risk differential. METHODS: The Taupo Bicycle Study involved 2590 adult cyclists recruited in 2006 and followed over a median period of 4.6 years through linkage to four national databases. The Auckland participants were compared with others in terms of baseline characteristics, crash outcomes and perceptions about environmental determinants of cycling. Cox regression modelling for repeated events was performed with multivariate adjustments. RESULTS: Of the 2554 participants whose addresses could be mapped, 919 (36%) resided in Auckland. The Auckland participants were less likely to be Maori but more likely to be socioeconomically advantaged and reside in an urban area. They were less likely to cycle for commuting and off-road but more likely to cycle in the dark and in a bunch, use a road bike and use lights in the dark. They had a higher risk of on-road crashes (hazard ratio: 1.47; 95% CI: 1.22, 1.76), of which 53% (95% CI: 20%, 72%) was explained by baseline differences, particularly related to cycling off-road, in the dark and in a bunch and residing in urban areas. They were more concerned about traffic volume, speed and drivers' behaviour. CONCLUSIONS: The excess crash risk in Auckland was explained by cycling patterns, urban residence and factors associated with the region's car-dominated transport environment.

Regional variations in pedal cyclist injuries in New Zealand: safety in numbers or risk in scarcity?

OBJECTIVE: To assess regional variations in rates of traffic injuries to pedal cyclists resulting in death or hospital inpatient treatment, in relation to time spent cycling and time spent travelling in a car. METHODS: Cycling injuries were identified from the Mortality Collection and the National Minimum Dataset. Time spent cycling and time spent travelling as a driver or passenger in a car/van/ute/SUV were computed from National Household Travel Surveys. There are 16 census regions in New Zealand, some of which were combined for this analysis to ensure an adequate sample size, resulting in eight regional groups. Analyses were undertaken for 1996-99 and 2003-07. RESULTS: Injury rates, per million hours spent cycling, varied widely across regions (11 to 33 injuries during 1996-99 and 12 to 78 injuries during 2003-07). The injury rate increased with decreasing per capita time spent cycling. The rate also increased with increasing per capita time spent travelling in a car. There was an inverse association between the injury rate and the ratio of time spent cycling to time spent travelling in a car. The expected number of cycling injuries increased with increasing total time spent cycling but at a decreasing rate particularly after adjusting for total time spent travelling in a car. CONCLUSIONS: The findings indicate a 'risk in scarcity' effect for New Zealand cyclists such that risk profiles of cyclists are likely to deteriorate if fewer people use a bicycle and more use a car. IMPLICATIONS: Cooperative efforts to promote cycling and its safety and to restrict car use may reverse the risk in scarcity effect.

Use of health care by young Asian New Zealanders: findings from a national youth health survey.

AIM: To examine the use of health services and perceived barriers to accessing health care among young Asian New Zealanders. METHODS: Secondary analysis of data from Youth2000, a cross-sectional survey of secondary school students in New Zealand (NZ) conducted in 2001. Of the 9567 survey participants (aged 12-18 years), this study was restricted to students who identified with an 'Asian' ethnic category (n = 922). RESULTS: Chinese and Indian students (the largest Asian ethnic groups in NZ) reported levels of overall health comparable to NZ European (NZE) students. However, relative to NZE students, Chinese students were more likely to report (i) not having a usual location for health care (adjusted OR 3.28; 95% CI: 2.51-4.43); and (ii) having problems getting health care when they needed it (adjusted OR 1.61; 95% CI: 1.32-1.96). Asian students who had been in NZ for 5 years or less (compared with NZ-born students), as well as those who did not speak English at home (compared with those who did) were less likely to report having a usual source of health care, even after adjusting for their overall health (adjusted OR 2.13, 95% CI: 1.27-3.56; and adjusted OR 1.69, 95% CI: 1.11-2.56, respectively). CONCLUSION: Young Asian New Zealanders are less likely to access health care than their NZE counterparts. The perceived barriers require explicit attention within the broader platforms of health-care quality, and professional and cultural competence of health-care services.

Drink driving and the patterns and context of drinking among New Zealand adolescents.

AIM: To examine the association between drink driving and the patterns and locations of usual drinking among New Zealand adolescents. METHODS: This is a secondary analysis of data from a nationally representative youth health survey, the sampling frame for which was all New Zealand secondary schools with more than 50 students enrolled in years 9 to 13 (ages 12 to 18 years) in 2001. The analysis was restricted to the 3408 survey respondents aged 15 years or older who were current drinkers and drivers. RESULTS: In total, 17.3% of participants reported drink driving in the previous month. Drink driving was significantly associated with frequent (at least weekly) alcohol use, binge drinking and usually drinking away from home, that is in cars, outdoors, at bars or nightclubs, at parties, at school and at work. Students' perception that parents and schools care about them, parental monitoring, and high academic achievement was associated with a reduced risk of drink driving while having friends who drink alcohol increased this risk. These associations were similar among boys and girls. CONCLUSION: The findings support calls to address how and where young people drink, and indicate the potential gains to be made with family- and school-based interventions.

Supermarket sales data: feasibility and applicability in population food and nutrition monitoring.

Population food and nutrition monitoring plays a critical role in understanding suboptimal nutrition at the population level, yet current monitoring methods such as national surveys are not practical to undertake on a continuous basis. Supermarket sales data potentially address this gap by providing detailed, timely, and inexpensive monitoring data for informing policies and anticipating trends. This paper reviews 22 studies that used supermarket sales data to examine food purchasing patterns. Despite some methodological limitations, feasibility studies showed promising results. The potential and limitations of using supermarket sales data to supplement food and nutrition monitoring methods are discussed.