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Background Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users. Methods Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004–12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients. Results Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up. Conclusions Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use. [ABSTRACT FROM AUTHOR]

Background and Aim: People with new‐onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new‐onset diabetes. Methods: We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti‐diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. Results: Among 99 687 women aged ≥ 50 years with new‐onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta‐blockers, acid disorder drugs, and lipid‐modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. Conclusions: Our model doubled the PPV of pancreatic cancer in women with new‐onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge. [ABSTRACT FROM AUTHOR]

: Objective: To determine the test‐retest repeatability of a self‐completed survey with items capturing skin cancer risk factors. Methods: We invited 238 randomly selected participants of the QSkin II cohort to complete the baseline survey a second time. Responses were compared using kappa statistics and intraclass correlation coefficients to quantify agreement for categorical and continuous variables, respectively. We compared the performance of key items with that observed in an earlier repeatability study using the same survey instrument in an independent cohort. Results: Measures of phenotypic characteristics had moderate to almost‐perfect test‐retest repeatability (e.g. eye colour weighted kappa (κ[sub.w]) = 0.87, 95% confidence interval [CI]: 0.81, 0.92). Items measuring sun exposure showed lower agreement (κ[sub.w] range 0.36‐0.54) compared with phenotypic characteristics (κ[sub.w] range 0.59‐0.87). Items relating to treatment of skin cancers demonstrated almost‐perfect test‐retest repeatability (e.g. excisions for skin cancers κ[sub.w] 0.85, 95%CI: 0.80, 0.89). In aggregate, the repeatability of key items was very similar across the two independent repeatability samples. Conclusion: Fair to almost‐perfect repeatability for self‐reported skin cancer risk factors was robust across independent and temporally distant cohorts. Implications for public health: These self‐assessed risk factors for skin cancer are repeatable and suitable for use in clinical practice and research., Skin cancer is Australia's ‘national cancer’; this nation suffers the highest incidence of cutaneous melanoma and keratinocyte cancer in the world.[sup.1-3] Ultraviolet radiation exposure is the principal environmental risk factor; [...]

ObjectivesThe International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE.Study designInterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data.Main outcome measuresHarmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes).ResultsInterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41-53), and that at the last follow-up was 56 years (IQR: 48-64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12-13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8-55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9-24.6%) and 5.1% (range 1.3-13.2%), respectively.ConclusionsThe scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons.

Background Cutaneous squamous cell carcinoma (cSCC) and melanoma have different associations with sun exposure. Objectives To compare trends in the incidence rates of cSCC and melanoma, to provide insight into changing patterns of exposure to ultraviolet radiation (UVR). Methods We compared trends in the incidence of cSCC and melanoma in seven susceptible populations residing at mid-to-high latitudes: Finland, Norway, Sweden, Denmark, Scotland, the Netherlands and Tasmania (Australia). We fitted Joinpoint models to describe trends in age-standardized incidence rates for melanoma and cSCC and calculated the average annual percentage rate of change for the period 1989–2020 (1989–2018 for Tasmania). We calculated the incident rate ratio (IRR) as the ratio of the age-standardized rates (European Standard Population) for cSCC to melanoma and conducted age–period–cohort modelling to compare age, period and cohort effects. Results The ratio of cSCC-to-melanoma incidence increased with proximity to the equator and over time. In the most recent time period, the incidence of cSCC was higher than the incidence of melanoma for men and women in all seven populations. While the ratio of cSCC-to-melanoma incidence was higher for men vs. women, in most countries the cSCC-to-melanoma IRR increased over time to a greater extent in women than in men. Melanoma incidence was higher among younger people and cSCC incidence was higher among older people; the age at which the incidence of cSCC overtook the incidence of melanoma was progressively younger with proximity to the equator. Conclusions Despite concerted international efforts to preserve the ozone layer over the past four decades resulting in significant reductions in surface ultraviolet B at mid-latitudes, the incidence of skin cancer, particularly cSCC, continues to rise in those regions. Our findings are consistent with a stronger association with age-associated cumulative sun exposure for cSCC vs. melanoma and suggest that women are currently receiving greater UV radiation exposure than in the past. [ABSTRACT FROM AUTHOR]

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.