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This systematic review examines the relationship with multiple myeloma (MM) risk for sunlight and vitamin D related exposures, including vitamin D supplementation, circulating 25-hydroxyvitamin D concentration, personal ultraviolet B radiation exposure, ambient solar irradiance and vitamin D receptor (VDR) gene polymorphisms We conducted a search for terms related to multiple myeloma, vitamin D, vitamin D receptor, ultraviolet radiation, sunlight, and single nucleotide polymorphism (SNP) using Ovid MEDLINE, Ovid EMBASE, Web of Science and Cochrane CENTRAL. Studies were assessed for risk of bias and quality using the RoB 2.0, ROBINS-E or Q-Genie tools. We identified 13 eligible studies: one randomised controlled trial, two cohort studies, and ten case-control studies, including one nested case-control study and one meta-analysis of genome-wide association studies. We conducted a qualitative synthesis; quantitative synthesis was not appropriate due to study heterogeneity and the small number of studies identified. There was insufficient evidence to support an effect of any sunlight or vitamin D related exposure on MM risk. No polymorphisms in VDR were found to be strongly related to risk for people of European ancestry. Of the identified studies, many had high risk of bias or were of lower quality. Few studies have investigated the association between sunlight and vitamin D related exposures and multiple myeloma risk. The scarcity of high-quality studies makes it difficult to evaluate potential effects of these exposures on MM risk. Further research is necessary to investigate the influence of vitamin D related exposures on risk of multiple myeloma.., Competing Interests: Declaration of Competing Interest S.J.H. declares consultancy and advisory board membership for AbbVie; consultancy and advisory board membership for and honoraria from Amgen; consultancy, honoraria, and advisory board membership for and research funding from Bristol Myers Squibb/Celgene, Janssen-Cilag, Novartis; consultancy for and research funding and honoraria from GSK; consultancy, advisory board membership, and investigator on studies for and honoraria from Roche/Genetec; consultancy and advisory board membership for and honoraria from Takeda; scientific advisory board membership for and research funding from Haemalogix; and consultancy and an advisory role for Sanofi. The funders had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report, or the decision to submit the paper for publication., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The influence of early-life growth pattern and body size on follicular lymphoma (FL) risk and survival is unclear. In this study, we aimed to investigate the association between gestational age, growth during childhood, body size, changes in body shape over time, and FL risk and survival., Methods: We conducted a population-based family case-control study and included 706 cases and 490 controls. We ascertained gestational age, growth during childhood, body size and body shape using questionnaires and followed-up cases (median=83 months) using record linkage with national death records. We used a group-based trajectory modeling approach to identify body shape trajectories from ages 5-70. We examined associations with FL risk using unconditional logistic regression and used Cox regression to assess the association between body mass index (BMI) and all-cause and FL-specific mortality among cases., Results: We found no association between gestational age, childhood height and FL risk. We observed a modest increase in FL risk with being obese 5 years prior to enrolment (OR=1.43, 95 %CI=0.99-2.06; BMI ≥30 kg/m 2 ) and per 5-kg/m 2 increase in BMI 5 years prior to enrolment (OR=1.14, 95 %CI=0.99-1.31). The excess risk for obesity 5 years prior to enrolment was higher for ever-smokers (OR=2.00, 95 %CI=1.08-3.69) than never-smokers (OR=1.14, 95 %CI=0.71-1.84). We found no association between FL risk and BMI at enrolment, BMI for heaviest lifetime weight, the highest categories of adult weight or height, trouser size, body shape at different ages or body shape trajectory. We also observed no association between all-cause or FL-specific mortality and excess adiposity at or prior to enrolment., Conclusion: We observed a weak association between elevated BMI and FL risk, and no association with all-cause or FL-specific mortality, consistent with previous studies. Future studies incorporating biomarkers are needed to elucidate possible mechanisms underlying the role of body composition in FL etiology., Competing Interests: Conflict of interest statement All authors declare that they have no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: With the prevalence of cancer survivors increasing, their unique needs must be better understood. We examined the health, lifestyles and social circumstances of adults with and without a history of cancer., Methods: We performed a cross-sectional study, using exposure and outcome data from the baseline survey (2006-2009) of participants in the 45 and Up Study, a prospective cohort study in New South Wales, Australia. We compared 20,811 cancer registry-verified adult cancer survivors with 207,148 participants without a history of cancer using propensity score weighting and accounting for multiple testing. The propensity weighting included age, sociodemographic factors and number of self-reported co-morbidities., Results: Cancer survivors were more likely to report poorer physical and psychological health and quality of life compared to those without a cancer history, with most deficits still evident more than 10 years after cancer diagnosis. Cancer survivors were more likely to have a higher body mass index, but were less likely to smoke. Cancer survivors had greater functional limitations, including sexual, and were less likely to work full time, volunteer and spend time outdoors. Their social connectedness was, however, similar. Those with haematological cancer, lung cancer, or distant metastases, and those diagnosed at an older age, had the greatest health deficits and functional limitations., Conclusions: A history of cancer is associated with poorer health and less paid and unpaid work. Our findings reinforce the importance of routine long-term, integrated multidisciplinary care for cancer survivors and indicate the subgroups with the greatest unmet needs., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain., Methods: A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared individuals with incident registry-notified CUP (n = 327; 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Results: In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk., Conclusion: Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia., Methods: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Results: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers., Conclusion: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Germ cell tumour (GCT) aetiology is uncertain and comprehensive epidemiological studies of GCT incidence are few., Methods: Nationwide data on all malignant GCTs notified to Australian population-based cancer registries during 1982-2011 were obtained. Age- and sex-specific, and World age-standardised incidence rates were calculated for paediatric (0-14) and adult (15+) cases using the latest WHO subtype classification scheme. Temporal trends were examined using Joinpoint regression., Results: There were 17,279 GCTs (552 paediatric, 16,727 adult). Age-specific incidence in males (all histologies combined) was bimodal, with peaks during infancy for most sites, and second, larger, peaks during young adulthood. Incidence of ovarian tumours peaked at age 15-19. Around half of paediatric tumours were extragonadal, whereas adult tumours were mostly gonadal. Yolk sac tumours and teratomas predominated in infants, whereas germinomas became more frequent towards adulthood. Increasing incidence trends for some adult gonadal tumours have stabilised; the trend for male extragonadal tumours is also declining., Conclusion: Broad similarities in the shape of age-specific incidence curves, particularly for gonadal, central nervous system, and mediastinal tumours provide epidemiological support for commonalities in aetiology among clinically disparate GCT subtypes. Differences in peak ages reflect underlying subtype-specific biological differences. Declining incidence trends for some adult gonadal tumours accords with the global transition in GCT incidence, and supports the possibility of a reduction in prevalence of shared aetiological exposures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Little is known about patterns of care after a cancer of unknown primary (CUP) diagnosis., Methods: We performed a retrospective cohort study to describe and compare the treatment, health service use and survival of patients with CUP and metastatic cancer of known primary among 143,956 Australian Government Department of Veterans' Affairs clients, 2004-2007. We randomly matched clients with CUP (C809; n=252) with clients with a first diagnosis of metastatic solid cancer of known primary (n=980). We ascertained health services from the month of diagnosis up to 2 months post-diagnosis for consultations, hospitalizations and emergency department visits, and up to 1 year for treatment. We compared cancer treatments using conditional logistic regression; consultation rates using negative binomial regression; and survival using stratified Cox regression., Results: 30% of CUP patients and 70% of patients with known primary received cancer treatment and the median survival was 37 days and 310 days respectively. CUP patients received fewer cancer medicines (odds ratio (OR)=0.54, 95% confidence interval (CI) 0.33-0.89) and less cancer-related surgery (OR=0.25, 95% CI 0.15-0.41); males with CUP received more radiation therapy (OR=2.88, 95% CI 1.69-4.91). CUP patients had more primary care consultations (incidence rate ratio (IRR)=1.25, 95% CI 1.11-1.41), emergency department visits (IRR=1.86, 95% CI 1.50-2.31) and hospitalizations (IRR=1.18, 95% CI 1.03-1.35), and a higher risk of death within 30 days (hazard ratio=3.30, 95% CI 1.69-6.44)., Conclusions: Patients with CUP receive less treatment but use more health services, which may reflect underlying patient and disease characteristics., (Copyright © 2015 Commonwealth of Australia. Published by Elsevier Ltd.. All rights reserved.)

Background: Population-based data on the use of health services and diagnostic investigations for patients with cancer of unknown primary (CUP) is scarce. It is uncertain whether the pathways to diagnosis are different for CUP compared to other cancers., Methods: We performed a population-based nested matched case-control study using linked routinely collected records for Australian Government Department of Veterans' Affairs clients, 2004-2007. We compared health care consultations, hospitalisations, emergency department visits, and diagnostic procedures in the three months prior and the month of diagnosis for 281 clients registered with a diagnosis of CUP (C809) and 1102 controls randomly selected from clients registered with a first diagnosis of metastatic cancer of known primary., Results: Overall, the median age at cancer diagnosis was 83 years. CUP patients were slightly older and had significantly more comorbidities prior to diagnosis than those with known primary. Compared to known primary, a diagnosis of CUP was significantly more likely after an emergency department visit, less specialist input, fewer invasive diagnostic procedures such as resection or endoscopy, and more non-invasive procedures such as magnetic resonance imaging. There were no differences in primary care or allied health consultations and hospitalisations., Conclusions: This health care pathway suggests delayed recognition of cancer and scope for improvement in the medical management of high-risk individuals presenting to primary care. The pattern of diagnostic investigations reveals under-investigation in some CUP patients but this is likely to reflect recognition of limited treatment options and poor prognosis and is consistent with clinical guidelines., (Copyright © 2015 Commonwealth of Australia. Published by Elsevier Ltd.. All rights reserved.)

Background: Cancer of unknown primary (CUP) is a common cancer yet little is known about the reliability of incidence data., Methods: We audited 574 CUP (C80.9) diagnoses (median age 81 years) registered by the New South Wales (NSW) Central Cancer Registry (2004-2007) in a cohort of Australian Government Department of Veterans' Affairs clients. The registry did not clarify diagnoses with notifiers during this period due to interpretation of privacy legislation. For the audit, current registry practice was applied by seeking additional information from CUP notifiers and reclassifying diagnoses as necessary. In addition, clinicopathological characteristics were extracted from notifications. Fisher's exact test and Student's t-test were used to compare the demographic and clinicopathological characteristics of the CUP subgroups. Age/sex-standardised CUP incidence rates and 95% confidence intervals were calculated, standardised to the 2001 Australian population., Results: 172 (30.0%) cases were reclassified to a known primary site, mostly cutaneous, and nine (1.6%) were found to be non-malignant diagnoses. After the audit the age/sex-standardised CUP incidence rates decreased from 26.0 (95% CI 21.2-30.8) to 15.9 (95% CI 12.5-19.3) per 100,000 person-years. Of the 393 remaining CUP cases, 202 (51%) were registered on the basis of a clinical diagnosis (46 by death certificate only) and 191 (49%) by pathological diagnosis (79 by cytology alone). Compared to cases with a pathological diagnosis, cases with a clinical diagnosis were older (85.6 vs. 82.0 years, p<0.001), and the reported number and location of metastases differed (p<0.001); metastatic sites were more likely to be unspecified for clinical diagnoses (36.1% vs. 4.2%)., Conclusions: Cancer registry processes can markedly influence CUP incidence. Future population-based CUP research should take this into account, and consider stratification by basis of diagnosis due to differences in patient and tumour characteristics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Epidemiological research often ascertains cancer history via self-reported questionnaires. We assessed the validity of self-reported cancer diagnoses in women born 1921-1926 recruited to the Australian Longitudinal Study in Women's Health (ALSWH) and determined the factors associated with false positive (FP) and false negative (FN) reporting. 4234 ALSWH cohort members were asked at baseline (1996) and in subsequent three-yearly surveys whether they had been diagnosed with specific cancers, including breast, cervical, lung and colorectal. We linked the cohort to the population-based New South Wales Central Cancer Registry (CCR) from 1972 to 2005 to identify registered invasive cancers. We calculated sensitivity, specificity and positive predictive value (PPV) of self-reported cancer diagnoses overall, at baseline (prevalent cancers) and follow-up (incident cancers) using the CCR diagnosis as the 'gold standard'. We used adjusted logistic regression to examine the determinants of FP and FN reports. Overall sensitivity was 89.2% (95% CI 86.0-91.7%) and exceeded 90% for breast, lung and colorectal cancer at baseline. Overall specificity was 96.9% (95% CI 96.3-97.5%), however, PPV was lower at 66.5% (95% CI 62.7-70.1%). FN reporting of any cancer at baseline was associated with being born overseas. Sensitivity and specificity of self-reported cancer diagnoses in this cohort of older women (aged 70-75 years at baseline) is high but PPV is comparatively lower. Hence, the use of linked data from population-based cancer registries is recommended for studies of cancer epidemiology. Particular attention must also be paid to country of birth in self-reported cancer data, as these findings suggest cancer will be under-reported by this group of women., (Copyright © 2011 Elsevier Ltd. All rights reserved.)