High parental occupational social contact and risk of childhood hematopoietic,brain and bone cancers

BackgroundThe etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers.MethodsWe examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973–2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis.ResultsAcute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67–1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34–0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03–2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02–2.32; paternal: OR: 1.82, 95% CI: 1.05–3.17).ConclusionOur results support the notion of a role of infections for some cancer types.     

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by ³²P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (+1.87 μmol GSH g^?1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.     

Insurance status as a modifier of the association between race and stage of prostate cancer diagnosis in Florida during 1995 and 2013

BackgroundCancer stage at diagnosis is a critical prognostic factor regarding a patient’s health outcomes. It has yet to be shown whether insurance status across different race has any implications on the stage of disease at the time of diagnosis. This study aimed to investigate whether insurance status was a modifier of the association between race and stage of previously undetected prostate cancer at the time of diagnosis in Florida between 1995 and 2013.MethodsSecondary data analysis of a cross-sectional survey using information from the Florida Cancer Data System (n = 224,819). Study participants included black and white males diagnosed with prostate cancer in Florida between 1995 and 2013. The main outcome variable was stage of prostate cancer at diagnosis. The main independent variable was race (black vs white). Adjusted logistic regression models were used to explore the association between race, insurance status and stage at diagnosis. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated.ResultsBlack males were more likely to be diagnosed with late stage prostate cancer (OR 1.31; 95% CI 1.27–1.35). Being uninsured (OR 2.28; 95% CI 2.13–2.45) or having Medicaid (OR 1.84; 95% CI 1.70–1.98) was associated with a diagnosis of late stage cancer. Stratified analysis for health insurance revealed that blacks had an increased risk for late stage cancer if uninsured (OR 1.29; 95% CI 1.07–1.55) and if having Medicare (OR 1.39; 95% CI 1.31–1.48).Conclusion: Insurance status may modify the effect of race on late stage prostate cancer in black patients.     

Occupational exposure to immunologically active agents and risk for lymphoma: The European Epilymph case–control study

ObjectivesAllergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma.MethodsThe Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998–2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases and 2296 controls with complete occupational history could be included in the analysis. Associations between HMW exposures and lymphoma were evaluated using pooled unconditional logistic regression analyses.ResultsIndividuals exposed to HMW agents had a non-statistically significant decreased risk of any lymphoma (OR, 0.88: 95% CI, 0.74–1.05) and of B-cell lymphoma (OR, 0.91; 95% CI, 0.76–1.09), and a significantly decreased risk for Hodgkin lymphoma (OR, 0.62; 95% CI, 0.40–0.98). A decrease in risk for lymphoma was found for exposure to latex (OR, 0.74; 95% CI, 0.55–0.99).ConclusionsFurther epidemiologic and mechanistic research is needed to confirm that occupational exposure to HMW agents predisposing to asthma can reduce the risk of lymphoma.     

Socioeconomic differences in prostate cancer treatment: A systematic review and meta-analysis

BackgroundSince the 1990s, most nations have had a reduction or stabilisation in prostate cancer mortality. However, socioeconomic differences in disease specific mortality and survival have persisted. This has been partially attributed to differences in treatment choices. The aim of this systematic review and meta-analysis was to describe and quantify socioeconomic differences in use of prostate cancer treatment in the literature.MethodsMEDLINE, CINAHL and Embase were searched from 01 January 2000–01 April 2021 to identify articles that reported use of prostate cancer treatment by socioeconomic status. Random effects meta-analysis was used to analyse socioeconomic differences in treatment where there was more than one study for treatment type. A modified version of the Newcastle-Ottawa Scale was used to assess risk of bias.ResultsOut of 7267 articles identified, eight met the inclusion criteria and six were analysed using meta-analysis. Meta-analysis could only be completed for non-active treatment (watchful waiting/active surveillance). Lower education was associated with non-active treatment (OR=0.90, [95% CI 0.83–0.98], p=0.02, I²=67%), however, level of income was not (OR=0.87, [CI 0.75–1.02], p=0.08, I²=94%). Sensitivity analysis of studies where active surveillance was the outcome (n=3), indicated no associations with level of income (OR=0.91, [95% CI 0.82–1.01], p=0.08, I²=52%) or education (OR=0.88, [95% CI 0.70–1.10], p=0.25, I²=79%). All studies were assessed as high-risk of bias.DiscussionThe relationship between socioeconomic status and prostate cancer treatment depended on the socioeconomic variable being used, the treatment type and how it was defined in research. Considerable methodological limitations were identified. Further research should improve on previous findings and address current gaps.     

Hysterectomy and risk of epithelial ovarian cancer by histologic type,endometriosis, and menopausal hormone therapy

BackgroundThis nationwide, register-based case-control study investigated the association between hysterectomy and risk of epithelial ovarian cancer according to histology and by history of endometriosis and menopausal hormone therapy (MHT) use.MethodsFrom the Danish Cancer Registry, all women registered with epithelial ovarian cancer at age 40–79 years during 1998–2016 were identified (n = 6738). Each case was sex- and age-matched to 15 population controls using risk-set sampling. Information on previous hysterectomy on benign indication and potential confounders was retrieved from nationwide registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer according to histology, endometriosis, and use of MHT.ResultsHysterectomy was not associated with risk of epithelial ovarian cancer overall (OR=0.99; 95% CI 0.91 –1.09) but was associated with reduced risk of clear cell ovarian cancer (OR=0.46; 95% CI 0.28–0.78). In stratified analyses, decreased ORs associated with hysterectomy were seen in women with endometriosis (OR=0.74; 95% CI 0.50–1.10) and in non-users of MHT (OR=0.87; 95% CI 0.76–1.01). In contrast, among long-term MHT users, hysterectomy was associated with increased odds for ovarian cancer (OR=1.20; 95% CI 1.03–1.39).ConclusionHysterectomy was not associated with epithelial ovarian cancer overall but with reduced risk of clear cell ovarian cancer. Our findings may suggest a reduced risk of ovarian cancer after hysterectomy in women with endometriosis and in MHT non-users. Interestingly our data pointed to an increased ovarian cancer risk associated with hysterectomy among long-term users of MHT.     

Birthweight and risk of thyroid cancer and its histological types: A large cohort study

BackgroundThe aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk.ObjectiveTo investigate if birthweight is associated with the later risk of thyroid cancer and its histological types.Methods246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936–1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI).ResultsDuring follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03–1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07–2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90–1.59] per kilogram).ConclusionA heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.     

Pre-diagnostic circulating p53 autoantibodies and subsequent lung cancer risk in low-income African and European Americans

IntroductionMutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking.MethodsIn this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies.ResultsAfter adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10–8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24–6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30–16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33–13.89).ConclusionOur findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.     

Male-origin microchimerism and endometrial cancer: A prospective case-cohort study

BackgroundMany women carry male cells of presumed fetal origin–so-called male-origin microchimerism (MOM)–in their circulation and tissues. Studies have found reduced risks of hormone dependent cancers, including breast and ovarian cancer, among MOM-positive women. The aim of this study was to investigate the association between MOM and endometrial cancer.MethodsWe designed a prospective case-cohort study including 76 cases and 505 controls from the Diet, Cancer and Health cohort aged 50–64 years and cancer-free at enrolment in 1993–1997. We analyzed blood samples for the presence of Y-chromosome (DYS14). We examined the association between MOM and endometrial cancer in weighted Cox regression models. As a negative control outcome, we studied the association between MOM and injuries to test for spurious associations.ResultsWe detected MOM in 65.9% controls and 54.0% cases. While we observed no overall association between MOM and endometrial cancer (HR=0.73, 95% CI: 0.47–1.15), we found a borderline significantly reduced rate of Type 1 endometrial cancer (HR=0.66, 95% CI: 0.39–1.00), but not other types of endometrial cancers (HR=1.00, 95% CI: 0.35–2.90). The reduced rate was not modified by hormonal exposure (P = 0.79). We found no association between MOM and risk of injuries (HR=0.96, 95% CI: 95% CI: 0.78–1.21).ConclusionsOur study suggests that MOM is inversely associated with Type 1 endometrial cancer, without evidence of an interaction with hormonal exposure. We encourage future research to confirm our findings.     

Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

Low-level environmental lead and cadmium exposures and dyslipidemia in adults: Findings from the NHANES 2005–2016

BackgroundPrevious experimental and occupational health studies have shown the toxic effects of relatively high-level cadmium and lead on lipid metabolism. However, limited studies investigated the relationships between serum lipid levels and exposure to low-level lead and cadmium in adults.ObjectiveTo investigate the associations between lead and cadmium levels in blood and dyslipidemia in adults.MethodsA retrospective cross-sectional study of 7,457 adults aged 20–79 years who were recruited in the National Health and Nutrition Examination Survey (NHANES, 2005–2016) was conducted. Multivariate linear and logistic regressions were used to examine the associations of blood lead and cadmium levels with serum lipid profiles and risk of dyslipidemia, respectively.ResultsThe weighted geometric means [95% confidence intervals (CIs)] of lead and cadmium in blood were 1.23 (1.21, 1.25) μg/dL and 0.36 (0.35, 0.37) μg/L, respectively. Blood lead was significantly associated with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (Apo B) levels after adjusting for covariates. Compared with the adults in the lowest blood lead quartile (≤0.76 μg/dL), those in the highest lead quartile (>1.90 μg/dL) had higher risks of elevated TC (OR = 1.88, 95% CI: 1.59–2.22), non-HDL-C (OR = 1.59, 95% CI: 1.33–1.91), LDL-C (OR = 1.68, 95% CI: 1.41–1.99) and Apo B (OR = 2.00, 95% CI: 1.46–2.73). However, the single effect of cadmium exposure and the joint effect of lead and cadmium exposures on dyslipidemia were not observed.ConclusionBlood lead well below the current recommended level was positively associated with the risk of dyslipidemia in adults, while the low-level cadmium exposure currently observed in adults did not show any significant associations with lipid levels.     

Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: A systematic review and meta‐analysis

Background Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated.ObjectiveThis study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients.Materials and methodsTo evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study.ResultsThe proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25–2.25, p < 0.001), while the rates of T3/T4 stage (OR 1.16, 95% CI 0.60–2.24, p = 0.65) and N1 stage (OR 0.99, 95% CI 0.65–1.51, p = 0.96) were not statistically correlated with AR-V7 status. The AR-V7-positive patients exhibited a significantly higher proportion of any site metastasis (61.3% versus 35.0%; OR 2.19, 95% CI 1.57–3.05, p < 0.001) and bone metastasis (81.7% versus 69.0%; OR 1.97, 95% CI 1.44–2.69, p < 0.001), and a trend close to significance was expected in visceral metastasis (28.8% versus 22.1%; OR 1.29, 95% CI 0.96–1.74, p = 0.09). Incidences of pain in AR-V7-positive CRPC (54.6%) were significantly higher than in negative CRPC (28.1%; OR 4.23, 95% CI 2.52–7.10, p < 0.001), line with worse ECOG performance status (56.7% versus 35.0%, OR 2.18, 95% CI 1.51–3.16, P < 0.001). Limitations of the study include differences in sample sizes and designs, AR-V7 detection assays, as well as disease characteristics of the included studies.ConclusionsAR-V7 positivity is associated with a higher Gleason score, bone or any site metastasis, pain and worse ECOG performance scores in CRPC. However, it is not correlated with tumor stage or lymph node metastasis. More studies are needed to confirm these findings.     

Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study

Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10⁻⁸) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for: I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI:0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI: 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI:1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI:-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI: -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for: I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI: 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI: 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

Demographic,social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP)

BackgroundLittle 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.MethodsBaseline 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).ResultsIn 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.ConclusionThe 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.     

Health-related predictors of cancer registry-notified cancer of unknown primary site (CUP)

BackgroundThe relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain.MethodsA 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).ResultsIn 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.ConclusionLow self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.     

Fathering of Dizygotic Twins and Risk of Prostate Cancer: Nationwide,Population-Based Case-Control Study

Background

An association between male fertility and risk of prostate cancer has been suggested, possibly through lower androgen levels in subfertile men. We evaluated male fertility in relation to risk of prostate cancer by assessing the frequency of fathering of dizygotic twins, a marker of high fertility, among cases of prostate cancer and controls.

Methods

We performed a case-control study in Prostate Cancer data Base Sweden (PCBaSe), a nationwide, population-based cohort. PCBaSe was linked to the Swedish twin register for information on zygosity for same-sex twins and to other nationwide health care registers and demographic databases for information on socioeconomic factors, comorbidity, and tumor characteristics for 96 301 prostate cancer cases and 378 583 matched controls. To account for the influence of in vitro fertilization on dizygotic twinning, analyses were restricted to men who had fathered children before 1991, when in vitro fertilization was still uncommon in Sweden.

Results

1 112 cases and 4 538 controls had fathered dizygotic twins. Men with dizygotic twins had no increased risk of prostate cancer compared to fathers of singletons; neither for total prostate cancer odds ratio (OR) 0.95(95% CI 0.89–1.02), nor for any risk category, OR 0.97 (95% CI 0.84–1.12) for low-risk disease, and OR 1.04 (95% CI 0.90–1.22) for metastatic disease.

Conclusion

The lack of association between fathering of dizygotic twins and prostate cancer risk give no support for an association between male fertility and prostate cancer risk.