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Background: We examined associations between two forms of testosterone therapy (TT) and risks of seven cancers among men., Methods: SEER-Medicare combines cancer registry data from the Surveillance, Epidemiology, and End Results programme with Medicare claims. Our population-based case-control study included incident cancer cases diagnosed between 1992-2015: prostate (n = 130,713), lung (n = 105,466), colorectal (n = 56,433), bladder (n = 38,873), non-Hodgkin lymphoma (n = 17,854), melanoma (n = 14,241), and oesophageal (n = 9116). We selected 100,000 controls from a 5% random sample of Medicare beneficiaries and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI)., Results: TT was associated with lower risk of distant-stage prostate cancer (injection/implantation OR = 0.72, 95% CI: 0.60-0.86; topical OR = 0.50, 95% CI: 0.24-1.03). We also observed inverse associations for distant-stage colorectal cancer (injection/implantation OR = 0.75, 95% CI: 0.62-0.90; topical OR = 0.11, 95% CI: 0.05-0.24). Risks of distant-stage colorectal and prostate cancers decreased with time after initiating TT by injection/implantation. By contrast, TT was positively associated with distant-stage melanoma (injection/implantation OR = 1.70, 95% CI: 1.37-2.11). TT was not associated with bladder cancer, oesophageal cancer, lung cancer or non-Hodgkin lymphoma., Conclusion: TT was inversely associated with distant-stage prostate and colorectal cancers but was positively associated with distant-stage melanoma. These observations may suggest an aetiologic role for TT or the presence of residual confounding., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Differential uptake of prostate-specific antigen testing in the US and UK has been linked to between-country differences for prostate cancer incidence. We examined stage-specific fatal prostate cancer incidence trends in the US and England, by treatment and race/ethnicity., Methods: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program and Public Health England's National Cancer Registration and Analysis Service, we identified prostate cancer patients diagnosed between 1995 and 2005, aged 45-84 years. Fatal prostate cancer was defined as death attributed to the disease within 10 years of diagnosis. We used age-period-cohort models to assess trends in fatal prostate cancer incidence., Results: Fatal prostate cancer incidence declined in the US by -7.5% each year and increased in England by 7.7% annually. These trends were primarily driven by locoregional disease in the US and distant disease in England. Black men in both countries had twofold to threefold higher fatal prostate cancer incidence rates, when compared with their white counterparts; however, receipt of radical prostatectomy lessened this disparity., Conclusions: We report a significant increasing rate of fatal prostate cancer incidence among English men. The black-white racial disparity appears pervasive but is attenuated among those who received radical prostatectomy in the US.

Background: Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk., Methods: We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals., Results: Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (P trend <0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, P trend =0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (P trend =0.02 and 0.03), but not non-aggressive disease (P trend =0.70 and 0.20; P heterogeneity =0.01 and 4.6 × 10 -3 ). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study., Conclusions: Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.

Background: Elevated body mass index (BMI, kg m -2 ) has been consistently associated with oesophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) incidence. However, effects of adiposity over the life course in relation to EA/GCA have not been thoroughly explored., Methods: We pooled two prospective cohort studies: NIH-AARP Diet and Health Study and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, with data on 409 796 individuals (633 EA, 415 GCA). At baseline, participants reported their height and weight at ages 20 and 50 years, and current. Body mass index trajectories were determined using latent class analysis. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression., Results: Compared with individuals with a BMI<25 kg m -2 at all time points, exceeding a BMI of 25 kg m -2 at age 20 was associated with increased risks of EA (HR=1.76, 95% CI: 1.35-2.29) and GCA (HR=1.62, 95% CI: 1.16-2.25). Similarly, a BMI trajectory of overweight (⩾25-<30 kg m -2 ) at age 20 progressing to obesity (⩾30 kg m -2 ) by age 50 was associated with increased risks of EA (HR=2.90, 95% CI: 1.67-5.04) and GCA (HR=4.07, 95% CI: 2.32-7.15), compared with individuals with a normal weight (⩾18.5-<25 kg m -2 ) trajectory. Weight gain of ⩾20 kg between age 20 and baseline was also associated with a two times increased risk of EA (HR=1.97, 95% CI: 1.43-2.73) and more modestly with GCA (HR=1.40, 95% CI: 0.96-2.05)., Conclusions: Being overweight in early adulthood and weight gain later in life were each associated with increased risks of EA and GCA. This underscores the potential of weight control programs for reducing EA and GCA risk.

Background: The absolute risk of oesophageal adenocarcinoma (EA) among individuals with Barrett's oesophagus (BE) is low and a majority of EA cases are diagnosed among individuals with no prior BE diagnosis. To ensure that insights from EA case-control studies are transferable to clinical management of BE populations, we conducted a case-case study to compare the clinical presentation, medical history and survival of EA cases with and without a prior BE diagnosis in the Surveillance, Epidemiology and End Results Medicare database., Methods: Eligible EA cases were diagnosed at age ⩾68 years during 1994-2009. There were 5271 EA cases in this study, 87% of which did not have a prior diagnosis of BE (EA-no prior BE)., Results: Multivariable case-case comparisons evidenced adverse associations of GERD, ever cigarette smoking, hypertension, dyslipidemia, weight loss, peptic ulcer and irritable bowel disease each in EA-prior BE compared with EA-no prior BE. Obesity, metabolic syndrome, impaired fasting glucose and diabetes did not differ between groups. EA-prior BE cases were diagnosed with less advanced disease, were more likely to undergo surgery and less likely to receive chemotherapy and radiotherapy, and had better overall mean survival (2.5 vs 1.4 years). This survival advantage persisted in the multivariable Cox model (HR=0.69, 95%CI: 0.60, 0.78), despite adjustment for many factors including stage, grade and clinical interventions., Conclusions: This study provides evidence that EA cases occurring among individuals previously diagnosed with BE are different from the large majority of EA cases that occur without a prior BE diagnosis. Regardless of whether these differences emanate from aetiology, biology and/or selection biases, they underscore the importance of a prudent approach in using knowledge from EAC case-control studies in the management of BE populations.

Background: It has been hypothesised that intrauterine exposures are important for subsequent prostate cancer risk. Prior epidemiological studies have used birthweight as a proxy of cumulative intrauterine exposures to test this hypothesis, but results have been inconsistent partly because of limited statistical power., Methods: We investigated birthweight in relation to prostate cancer in the Medical Research Council (MRC) National Survey of Health and Development (NSHD) using Cox proportional hazards models. We then conducted a meta-analysis of birthweight in relation to total and aggressive/lethal prostate cancer risks, combining results from the NSHD analysis with 13 additional studies on this relationship identified from a systematic search in four major scientific literature databases through January 2015., Results: Random-effects models found that per kg increase in birthweight was positively associated with total (OR=1.02, 95% confidence interval (95% CI)=1.00, 1.05; I(2)=13%) and aggressive/lethal prostate cancer (OR=1.08, 95% CI=0.99, 1.19; I(2)=40%). Sensitivity analyses restricted to studies with birthweight extracted from medical records demonstrated stronger positive associations with total (OR=1.11, 95% CI=1.03, 1.19; I(2)=0%) and aggressive/lethal (OR=1.37, 95% CI=1.09, 1.74; I(2)=0%) prostate cancer. These studies heavily overlapped with those based in Nordic countries., Conclusions: This study provides evidence that heavier birthweight may be associated with modest increased risks of total and aggressive/lethal prostate cancer, which supports the hypothesis that intrauterine exposures may be related to subsequent prostate cancer risks.

Background: Middle-aged obese adults are at substantially elevated risk of oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in life., Methods: We assessed associations between childhood body mass index (BMI) and height-measured annually between ages 7 and 13-with adult oesophageal adenocarcinoma in a cohort from the Copenhagen School Health Records Register. Analyses included 255 053 children born during 1930-1971. Danish Cancer Registry linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression., Results: During 5.4 million person-years of follow-up, 254 (216 males) incident oesophageal adenocarcinomas occurred. At each examined age, cancer risk increased linearly per unit BMI z-score, although associations were only statistically significant for ages 9-13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per unit BMI z-score. Associations were similar in men and women and across birth cohorts. Childhood height was not related to cancer risk in men but was in women, although these analyses included just 38 female cases. HRs per unit height z-score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27, 2.47) in females, with similar results observed at the other examined ages., Conclusion: Individuals with higher childhood BMI were at elevated risk of oesophageal adenocarcinoma, even though these cancers occurred many decades later in life. Although the mechanisms require further investigation, our findings provide additional evidence for the long-term health risks of childhood obesity.

Background: Prostate cancer aetiology is poorly understood. It may have origins early in life; previously we found a positive association with childhood height. The effects of early life body mass index (BMI; kg m(-2)) on prostate cancer remain equivocal. We investigated if childhood BMI, independently and adjusted for height, is positively associated with adult prostate cancer., Methods: Subjects were a cohort of 125208 boys formed from the Copenhagen School Health Records Register, born 1930-1969 with height and weight measurements at 7-13 years. Cases were identified through linkage to the Danish Cancer Registry. Cox proportional hazards regressions were performed., Results: Overall, 3355 men were diagnosed with prostate cancer. Body mass index during childhood was positively associated with adult prostate cancer. The hazard ratio of prostate cancer was 1.06 (95% confidence interval (CI): 1.01-1.10) per BMI z-score at age 7, and 1.05 (95% CI: 1.01-1.10) per BMI z-score at age 13. Estimates were similar and significant at all other ages. However, adjustment for childhood height attenuated the associations at all but the youngest ages as most estimates became nonsignificant., Conclusions: These results suggest that at most childhood ages, BMI does not confer an additional risk for prostate cancer beyond that of height.

Background: Studies assessing the relationships of anthropometry and testicular germ-cell tumour (TGCT) have reported heterogeneous findings., Methods: We undertook a systematic review and meta-analysis of the associations between adult height, weight, body mass index (BMI), and testicular cancer. Search strategies were conducted in PubMed, EMBASE, Scopus, and Web of Science on 26 May 2009. Studies that met our inclusion criteria were included in meta-analytic models using STATA 11., Results: A total of 3255 references were retrieved, of which 14 met the inclusion criteria. Random effects meta-analysis found adult height (odds ratio (OR) per 5-cm increase 1.13, 95% confidence interval (CI) 1.07-1.19, P<0.001) and weight (OR overweight vs normal 0.92, 95% CI 0.86-0.98, P=0.011) to be associated with TGCT. The meta-analysis of weight and TGCT produced a summary estimate, which indicated no association, although an analysis restricted studies to North American was suggestive of association (OR per 1-kg increase 1.01, 95% CI 1.00-1.01, P<0.001)., Conclusions: This systematic review and meta-analysis has found evidence for a positive association of adult height and TGCT, and tentative evidence for an inverse association of BMI and TGCT.

Background: In the United States, the rates and temporal trends of oesophageal cancer overall and for the two predominant histologic types - adenocarcinoma (ADC) and squamous cell carcinoma (SCC) - differ between Blacks and Whites, but little is known with regard to the patterns among Asians/Pacific Islanders or Hispanics., Methods: Using the Surveillance, Epidemiology, and End Results programme data, we analysed oesophageal cancer incidence patterns by race, sex, and histologic type for the period 1977-2005., Results: Total oesophageal cancer incidence has been increasing among Whites only; the rates among all other race groups have declined. Moreover, rates among White men surpassed those among Blacks in 2004. Oesophageal SCC rates have been decreasing among virtually all racial/ethnic groups; rates among Hispanic and Asian/Pacific Islander men have been intermediate to those of Blacks and Whites, with rates among women being lower than those among Blacks or Whites. The ADC rates among Hispanic men may be rising, akin to the historical trends among Whites and Blacks. The sex ratios for these cancers also varied markedly., Conclusions: These observations may provide clues for aetiological research.

The US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study of testicular germ-cell tumours (TGCTs) enrolled participants and their mothers in 2002-2005. Hours of sports or vigorous childhood physical activity per week were ascertained for three time periods; 1st-5th grades, 6th-8th grades and 9th-12th grades. Son- and mother-reports were analysed separately and included 539 control son-mother pairs and 499 case son-mother pairs. Odds ratios and 95% confidence intervals were produced. The analysis of the sons' responses found no relationship between childhood physical activity and TGCT, while the mothers' analysis found an inverse association, which was solely due to nonseminoma. Future studies should seek to validate responses further using recorded information sources such as school records.