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Background Height and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach. Methods We identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height. Results Based on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91–1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02–1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results. Conclusions These findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status.

Background Observational studies have reported survival benefits associated with non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and non-aspirin NSAIDs (NA-NSAIDs), especially new use post-diagnosis, in women with ovarian cancer (OC). Methods Participants were women aged 18-79 diagnosed with OC in Australia, 2012-2015. Information was gathered through self-completed 3-monthly questionnaires and prescription records. Exposure was defined as any use (NA-NSAIDs/regular-dose aspirin □1/week or daily low-dose aspirin) during the year pre-diagnosis and first year post-diagnosis. We measured overall survival from start of primary treatment (surgery/neoadjuvant chemotherapy) (pre-diagnosis use) or from 12 months after the start of therapy (post-diagnosis) until the earliest of date of death/last follow-up/5 years. Cox proportional hazards regression was used to estimate survival. We also applied inverse-probability of treatment weighting (IPTW), which balances comparison groups regarding potential confounders. Results We observed improved survival associated with pre-diagnosis use of aspirin/NA-NSAIDs ≥4 days/week (frequent-users) compared to Conclusions Our findings suggest aspirin/NA-NSAID use might improve survival in women with OC. Larger cohorts or, preferably, a randomised controlled trial could clarify these findings. Key messages Use of aspirin/NA-NSAIDs may improve OC survival.

Background Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, has a five-year survival of ∼45%, and very few established modifiable risk factors. Some evidence suggests that bisphosphonates could have chemopreventive benefits, but few epidemiological studies have investigated the association between bisphosphonate use and incidence of EOC. Methods We conducted a nested case-control study using linked administrative data. We identified 9,367 women over 50 years diagnosed with EOC (cases) from 2004 to 2013, and for each case identified five controls from the Australian Medicare Enrolment database matched by age, state, area of residence, and area-level socioeconomic disadvantage. We assessed the associations between bisphosphonate use using dispensed prescription data (ever use, duration and dose) and EOC (overall, by histotype), adjusting for comorbidities and MHT use. We conducted sensitivity analyses in women with complete ascertainment of dispensing claims and for residents of one Australian state that had linked with data linked to hospital procedures, including oophorectomy. Results Our analyses show an inverse association between bisphosphonate use and risk of EOC overall (OR = 0.81, 95%CI:0.75-0.88), and for endometrioid (OR = 0.51, 95%CI:0.33-0.79) and serous (OR = 0.84, 95%CI:0.75-0.93) histotypes. There was some evidence that higher dose and duration were associated with a greater reduction in risk. Results from sensitivity analyses were not appreciably different. Conclusions Bisphosphonate use was associated with lower risk of EOC, suggesting bisphosphonates may reduce risk of ovarian cancer development. Key messages Bisphosphonates may protect against development of serous and endometrioid ovarian cancers.

Background Observational studies link vitamin D deficiency with acute respiratory tract infection (ARTI) but results from randomised controlled trials are heterogeneous. Methods We used data from The D-Health Trial (N = 21,315); ARTI was a pre-specified trial outcome. Participants were men and women aged 60 to 79 years (with volunteers aged up to 84 years), supplemented with monthly doses of 60,000 international units of vitamin D and followed for up to 5 years. Participants were asked to report occurrence of ARTI over the previous month via annual surveys, and a subset of participants completed 8-week respiratory symptom diaries in winter. We used regression models to estimate odds ratios, rate ratios and rate differences. Results Vitamin D supplementation did not reduce the risk of ARTI (survey OR 0.98, 95% CI 0.93 to 1.02; diary OR 0.98, 95% CI 0.83 to 1.15). Analyses of diary data showed that vitamin D reduced the average duration by 0.5 days (95% CI 0.2 to 0.7 days) and the average number of days with severe symptoms by 0.4 days (95% CI 0.3 to 0.6 days). Conclusions Monthly bolus doses of 60,000 IU of vitamin D did not reduce the overall risk of ARTI but slightly reduce the duration of symptoms in the general population. Key messages The reduction in the duration of symptoms suggests a potential impact of vitamin D on the immune response to infection.

Background Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4–21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. Methods Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). Results An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85–0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65–0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. Conclusion Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

Contains fulltext : 170949.pdf (Publisher’s version ) (Closed access) BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.

The QSkin Sun and Health Study comprises a cohort of 43 794 men and women aged 40-69 years randomly sampled from the population of Queensland, Australia in 2011. The cohort was established to study the development of skin cancer and melanoma in the population with the highest reported incidence of these diseases in the world. At baseline, besides demographic items and general medical history, information about standard pigmentary characteristics (including hair and eye colour, freckling tendency, tanning ability and propensity to sunburn), past and recent history of sun exposure and sunburns, sun protection behaviours, use of tanning beds and history of skin cancer was collected by self-completed questionnaire. Participants have given their consent for data linkage to the universal national health insurance scheme and for linkage to cancer registries and pathology databases, thus ensuring complete ascertainment of all future skin cancer and melanoma occurrences and medical treatments and other cancer events. Linkage to these registers will occur at predetermined intervals. Approval to access QSkin data can be obtained on application to the study investigators and submission of a formal research plan that has previous approval from the human research ethics committee of the applicant's institution.