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Purpose Prostate cancer is the second most common cancer in men and a leading cause of cancer mortality worldwide. Men with drug use disorders (DUD) may potentially be at high risk for prostate cancer mortality because of delayed diagnosis and/or undertreatment. In this study, we aimed to investigate prostate cancer incidence, mortality, and stage at time of diagnosis among men with DUD compared to the general male population in Sweden. Methods We performed a follow-up study based on Swedish national register data for the period January 1997–December 2016. The study was based on 1,361,532 men aged 50–75 years at inclusion, of whom 9,259 were registered with DUD. Cox regression analysis was used to compute adjusted hazard ratios (HRs) for incident and fatal prostate cancer, and cancer stage at time of diagnosis, associated with DUD. Results DUD was associated with a slightly increased risk of incident prostate cancer (HR: 1.07, 95% confidence interval [CI] 1.00–1.14, p = 0.048) and substantially higher risk of fatal prostate cancer (HR: 1.59, 95% CI 1.40–1.82, p Conclusions Men with DUD have an increased risk of fatal prostate cancer, possibly related to undertreatment in this patient population. Our findings should raise attention among medical staff and decision-makers towards a disadvantaged group of men in need of easily accessible prostate cancer evaluation and treatment.

Background Colorectal cancer (CRC) is the second most common cause of cancer death in Canada. Immigrants in Ontario, Canada’s most populous province, are known to have lower rates of CRC screening, but differences in stage of CRC diagnosis are not known. Methods We utilized linked administrative databases to compare early (stage I–II) versus late (stage III–IV) stage of CRC diagnosis for immigrants versus long-term residents among patients diagnosed in Ontario between 2012 and 2017 (n = 37,717) and examined the association of immigration-related, sociodemographic, and healthcare-related factors with stage. Results Almost 45% of those with CRC were diagnosed at a late stage. Immigrants were slightly more likely to be diagnosed at a late stage than their long-term resident counterparts [Adjusted relative risks (ARRs) 1.06 (95% CI 1.02–1.10)], but after adjusting for age and sex, this difference was no longer significant. In fully adjusted models, we observed a higher likelihood of late-stage diagnosis for people with the fewest co-morbidities (ARR 0.86 [95% CI 0.83–0.89]) and those with no visits to primary care (versus a high level of continuity of care) [ARR 1.07 (95% CI 1.03–1.12)]. Conclusion Immigrants were not more likely to have a late-stage CRC diagnosis after adjusting for relevant factors, but access to primary care and healthcare contact was significantly associated with diagnostic stage. Impact Attachment to a primary care provider who provides regular preventive care may play a role in more favorable stage at diagnosis for CRC and thus should be a healthcare system priority.

Purpose Through screening and HPV vaccination, cervical cancer can mostly be prevented or detected very early, before symptoms develop. However, cervical cancer persists, and many women are diagnosed at advanced stages. Little is known about the degree to which U.S. women may begin their diagnostic workup for cervical cancer in Emergency Departments (ED). We sought to quantify the proportion of women presenting symptomatically in the ED prior to their diagnosis with cervical cancer and to describe their characteristics and outcomes. Methods We identified women diagnosed from 2006 to 2017 with cervical cancer in the California Cancer Registry. We linked this cohort to statewide ED discharge records to determine ED use and symptoms present at the encounter. Multivariable logistic regression models examined associations with ED use and multivariable Cox proportional hazards regression models examined associations with survival. Results Of the more than 16,000 women with cervical cancer in the study cohort, 28% presented symptomatically in the ED prior to diagnosis. Those presenting symptomatically were more likely to have public (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.06–1.27) or no insurance (OR 4.81; CI 4.06–5.71) (vs. private), low socioeconomic status (SES) (OR 1.76; CI 1.52–2.04), late-stage disease (OR 5.29; CI 4.70–5.96), and had a 37% increased risk of death (CI 1.28–1.46). Conclusion Nearly a third of women with cervical cancer presented symptomatically, outside of a primary care setting, suggesting that many women, especially those with low SES, may not be benefiting from screening or healthcare following abnormal results.

Purpose Cardiotoxicity affects 5–16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. Methods A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s Q test and the I2 test. Results Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27–0.78), p = 0.004, $${ }I^{2}$$ I 2 = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17–1.45), p = 0.20, $$I^{2}$$ I 2 = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75–9.52), p $$I^{2}$$ I 2 = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82–11.68, p = 0.024, $$I^{2}$$ I 2 = 80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusion This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. Trial Registration Number and Date of Registration PROSPERO: CRD42020140352 on 7/6/2020.

Objectives To estimate observed and relative survival of prostate cancer patients in sub-Saharan Africa (SSA) and to examine the influence of age, stage at diagnosis and the Human Development Index (HDI). Patients and methods In this comparative registry study, we selected a random sample of 1752 incident cases of malign prostatic neoplasm from 12 population-based cancer registries from 10 SSA countries, registered between 2005 and 2015. We analyzed the data using Kaplan-Meier and Ederer II methods to obtain outcome estimates and flexible Poisson regression modeling to calculate the excess hazards of death Results For the 1406 patients included in the survival analyses, 763 deaths occurred during 3614 person-years of observation. Of patients with known stage, 45.2% had stage IV disease, 31.2% stage III and only 23.6% stage I and II. The 1 and 5-year relative survival for the entire cohort was 78.0% (75.4–80.7) and 60.0% (55.7–64.6), while varying between the registries. Late presentation was associated with increased excess hazards and a 0.1 increase in the HDI was associated with a 20% lower excess hazard of death, while for age at diagnosis no association was found. Conclusions We found poor survival of SSA prostatic tumor patients, as well as high proportions of late stage presentation, which are associated with inferior outcome. This calls for investment in health-care systems and action regarding projects to raise awareness among the population to achieve earlier diagnosis and improve survival.

Purpose The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case–control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. Methods Cases were non-Hispanic Black (NHB) and White (NHW) women age 20–49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010–2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. Results Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. Conclusions Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.

Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

Purpose To assess the change in mammography screening attendance in Sweden—overall and in sociodemographic groups at risk of low attendance—after removal of the out-of-pocket fee in 2016. Methods Individual-level data on all screening invitations and attendance between 2014 and 2018 were linked to sociodemographic data from Statistics Sweden. Odds ratios and 95% confidence intervals (CIs) for attendance by time period and sociodemographic factor were computed using mixed logistic regression to account for repeated measures within women. The study sample included 1.4 million women, aged 40–75, who had a mammography screening appointment in 2014–2015 and/or 2017–2018 in 14 of Sweden’s 21 health care regions. Results Overall screening attendance was 83.8% in 2014–2015 and 84.1% in 2017–2018 (+ 0.3 percentage points, 95% CI 0.2–0.4). The greatest increase in attendance was observed in non-Nordic women with the lowest income, where attendance rose from 62.9 to 65.8% (+ 2.9 points, 95% CI 2.3–3.6), and among women with four or more risk factors for low attendance, where attendance rose from 59.2 to 62.0% (+ 2.8 points, 95% CI 2.2–3.4). Conclusion Screening attendance did not undergo any important increase after implementing free screening, although attendance among some sociodemographic groups increased by almost three percentage points after the policy change.

African Americans and Appalachians experience greater incidence and mortality rates of colorectal cancer due to factors, such as reduced prevalence of screening. An educational session (the Screen to Save Initiative) was conducted to increase intent to screen for colorectal cancer among African Americans and Appalachians in Ohio. Using a community-based approach, from April to September 2017, 85 eligible participants were recruited in Franklin County and Appalachia Ohio. Participants completed a knowledge assessment on colorectal cancer before and after participating in either an educational PowerPoint session or a guided tour through an Inflatable Colon. Logistic regression models were used to determine what factors were associated with changes in colorectal cancer knowledge and intent to screen for colorectal cancer. The majority (71.79%) of participants gained knowledge about colorectal cancer after the intervention. Multivariate results showed that race (OR = 0.30; 95% CI: 0.11–0.80 for African Americans versus White participants) and intervention type (OR = 5.97; 95% CI: 1.94–18.43 for PowerPoint versus Inflatable Colon) were associated with a change in knowledge. The association between education and intent to screen was marginally statistically significant (OR = 0.42; 95% CI: 0.16–1.13 for college graduate versus not a college graduate). A change in colorectal cancer knowledge was not associated with intent to screen. Future educational interventions should be modified to increase intent to screen and screening for colorectal cancer. Further research with these modified interventions should aim to reduce disparities in CRC among underserved populations while listening to the voices of the communities.

Purpose There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged Methods A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. Conclusion Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.

Introduction Esophageal cancer (EC) is an aggressive malignancy with poor prognosis. Mortality and disease stage at diagnosis are important indicators of improvements in cancer prevention and control. We examined United States trends in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) mortality and stage at diagnosis by race and ethnicity. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to identify individuals with histologically confirmed EAC and ESCC between 1 January 1992 and 31 December 2016. For both EAC and ESCC, we calculated age-adjusted mortality and the proportion presenting at each stage by race/ethnicity, sex, and year. We then calculated the annual percent change (APC) in each indicator by race/ethnicity and examined changes over time. Results The study included 19,257 EAC cases and 15,162 ESCC cases. EAC mortality increased significantly overall and in non-Hispanic Whites from 1993 to 2012 and from 1993 to 2010, respectively. EAC mortality continued to rise among non-Hispanic Blacks (NHB) (APC = 1.60, p = 0.01). NHB experienced the fastest decline in ESCC mortality (APC = − 4.53, p Conclusion We found notable differences in trends in EAC and ESCC mortality and stage at diagnosis by race/ethnicity. Stage migration resulting from improvements in diagnosis and treatment may partially explain recent trends in disease stage at diagnosis. Future efforts should identify factors driving current esophageal cancer disparities.

Aim To examine patterns of recent pre-diagnostic fillings of antibiotics as an indicator of early symptoms of lung cancer. Methods Individuals diagnosed with lung cancer (cases) in 2009–2016 were identified in the Swedish National Lung Cancer Register, a population-based register, and randomly matched with up to five individuals free of lung cancer (controls) from the general population. Conditional logistic models were used to estimate odds ratios for the association between lung cancer and a recent history of filled antibiotic prescriptions. Results The study included 27,017 cases and 129,355 controls. The likelihood of recent exposure was approximately two times higher in cases compared to controls. The magnitude of the effect size became more pronounced with proximity to the diagnosis of lung cancer and an increasing number of filled prescriptions. While the magnitude of the effect size did not differ by sex or educational level, it became attenuated with increasing age. There was no evidence supporting a trend in the magnitude of the effect size for the association between lung cancer and a history of repeated fillings by cancer stage. Conclusion Lung cancer was associated with an increased likelihood of a recent history of filled antibiotic prescriptions. However, there was no evidence of an association between repeated fillings and a diagnostic delay, as reflected by stage. Our findings underscore the importance of clinical reassessment to rule out lung cancer following pneumonia treatment, especially for patients with multiple treatment cycles.

Background In response to the prioritization of healthcare resources towards the COVID-19 pandemic, routine cancer screening and diagnostic have been disrupted, potentially explaining the apparent COVID-era decline in cancer cases and mortality. In this study, we identified temporal trends in public interest in cancer-related health information using the nowcasting tool Google Trends. Methods We used Google Trends to query search terms related to cancer types for short-term (September 2019–September 2020) and long-term (September 2016–September 2020) trends in the US. We compared average relative search volumes (RSV) for specified time ranges to detect recent and seasonal variation. Results General search interest declined for all cancer types beginning in March 2020, with changes in search interest for “Breast cancer,” “Colorectal cancer,” and “Melanoma” of − 30.6%, − 28.2%, and − 26.7%, respectively, and compared with the mean RSV of the two previous months. In the same time range, search interest for “Telemedicine” has increased by + 907.1% and has reached a 4-year peak with a sustained increased level of search interest. Absolute cancer mortality has declined and is presently at a 4-year low; however, search interest in cancer has been recuperating since July 2020. Conclusion We observed a marked decline in searches for cancer-related health information that mirrors the reduction in new cancer diagnoses and cancer mortality during the COVID-19 pandemic. Health professions need to be prepared for the coming demand for cancer-related healthcare, foreshadowed by recovering interest in cancer-related information on Google Trends. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-021-01409-1.

Purpose To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. Methods A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. Results In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13–3.38) but not adjusted (HR 1.70 95% CI 0.95–3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. Conclusions In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival.

Background: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies.Objective: We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.Design: A genetic instrument was constructed using 5 single nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (N ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI: 0.63-1.08; P=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI: 0.57-1.70; P=0.93).Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

Prior studies of squamous cell carcinoma of the head and neck (SCCHN) have explored the effect of socioeconomic status (SES) as an independent risk factor; however, none have investigated the interaction of known risk factors with SES. We examined this using the North Carolina Head and Neck Cancer Epidemiology Study, a population-based case–control study. Incident cases of SCCHN from North Carolina between 2002 and 2006 (n = 1,153) were identified and age, sex, and race-matched controls (n = 1,267) were selected from driver license records. SES measures included household income, educational attainment, and health insurance. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Current smoking was more strongly associated with SCCHN among those households making $50,000/year [OR 2.47 (1.69–3.25); p interaction $50,000/year [1.28 (0.97–1.58); p interaction

Purpose In Trinidad and Tobago (TT), prostate cancer (CaP) is the most commonly diagnosed malignancy and the leading cause of cancer deaths among men. TT currently has one of the highest CaP mortality rates in the world. Methods 6,064 incident and 3,704 mortality cases of CaP occurring in TT from January 1995 to 31 December 2009 reported to the Dr. Elizabeth Quamina Cancer population-based cancer registry for TT, were analyzed to examine CaP survival, incidence, and mortality rates and trends by ancestry and geography. Results The age-standardized CaP incidence and mortality rates (per 100,000) based on the 1960 world-standardized in 2009 were 64.2 and 47.1 per 100,000. The mortality rate in TT increased between 1995 (37.9 per 100,000) and 2009 (79.4 per 100,000), while the rate in the US decreased from 37.3 per 100,000 to 22.1 per 100,000 over the same period. Fewer African ancestry patients received treatment relative to those of Indian and mixed ancestry (45.7%, 60.3%, and 60.9%, respectively). Conclusions Notwithstanding the limitations surrounding data quality, our findings highlight the increasing burden of CaP in TT and the need for improved surveillance and standard of care. Our findings highlight the need for optimized models to project cancer rates in developing countries like TT. This study also provides the rationale for targeted screening and optimized treatment for CaP to ameliorate the rates we report. Electronic supplementary material The online version of this article (10.1007/s10552-018-1038-8) contains supplementary material, which is available to authorized users.

Purpose The insulin-like growth factor (IGF) system is modifiable by diet and lifestyle, and has been linked to prostate cancer development and progression. Methods We conducted a prospective cohort study of 621 men diagnosed with localized prostate cancer to investigate the associations of dietary and lifestyle changes with post-diagnosis circulating levels of IGF-I and IGFBP-3. We used analysis of covariance to estimate the associations, controlling for baseline IGF-I or IGFBP-3, respectively. Results Mean IGF-I levels were 6.5% (95% CI −12.8, −0.3%, p = 0.04) lower in men who decreased their protein intake after diagnosis compared to men who did not change. Men who changed their fruit and vegetable intake had lower IGF-I levels compared to non-changers [Decreased intake: −10.1%, 95% CI −18.4, −1.8%, p = 0.02; Increased intake: −12.0%, 95% CI −18.4, −1.8%, p = 0.002]. IGFBP-3 was 14.6% (95% CI −24.5, −4.8%, p = 0.004) lower in men who achieved a healthy body mass index after diagnosis. Men who became inactive had 9.5% higher average IGF-I levels (95% CI 0.1, 18.9%, p = 0.05). Conclusions Decreased protein intake and body mass index, and increased physical activity and fruit and vegetable intake, following a prostate cancer diagnosis were associated with reduced post-diagnosis serum IGF-I and IGFBP-3. Counterintuitively, reduced fruit and vegetable intake was also associated with reduced IGF-I, but with weak statistical support, possibly implicating chance. If confirmed in other studies, our findings may inform potential lifestyle interventions in prostate cancer. ProtecT was registered at International Standard Randomised Controlled Trial Registry, http://isrctn.org as ISRCTN20141297.

Purpose To date, the role of meat and fish intake in head–neck cancer (HNC) etiology is not well understood and prospective evidence is limited. This prompted us to study the association between meat, fish, and HNC subtypes, i.e., oral cavity cancer (OCC), oro- and hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), within the Netherlands Cohort Study (NLCS). Methods In 1986, 120,852 participants (aged 55–69 years) completed a baseline 150-item food frequency questionnaire (FFQ), from which daily meat and fish intake were calculated. After 20.3 years of follow-up, 430 HNC overall (134 OCC, 90 OHPC and 203 LC) cases and 4,111 subcohort members were found to be eligible for case–cohort analysis. Multivariate hazard ratios were calculated using Cox’s proportional hazards model within quartiles of energy-adjusted meat and fish intake. Results Processed meat intake, but not red meat intake, was positively associated with HNC overall [HR(Q4 vs. Q1) = 1.46, 95% CI 1.06–2.00; ptrend = 0.03]. Among HNC subtypes, processed meat was positively associated with OCC, while no associations were found with OHPC and LC. Fish intake was not associated with HNC risk. Tests for interaction did not reveal statistically significant interaction between meat, fish, and alcohol or smoking on HNC overall risk. Conclusions In this large cohort study, processed meat intake was positively associated with HNC overall and HNC subtype OCC, but not with OHPC and LC. Electronic supplementary material The online version of this article (doi:10.1007/s10552-017-0892-0) contains supplementary material, which is available to authorized users.

Purpose Tobacco smoking and alcohol consumption are risk factors for several types of cancer and may act as confounders in aetiological studies. Large register-based cohorts often lack data on tobacco and alcohol. We present a method for computing estimates of cancer risk adjusted for tobacco and alcohol without exposure information. Methods We propose the use of confirmatory factor analysis models for simultaneous analysis of several cancer sites related to tobacco and alcohol. In the analyses, the unobserved pattern of smoking habits and alcohol drinking is considered latent common factors. The models allow for different effects on each cancer site, and also for appropriate latent site-specific factors for subgroup variation. Results may be used to compute expected numbers of cancer from reference rates, adjusted for tobacco smoking and alcohol consumption. This method was applied to results from a large, published study of work-related cancer based on census data (1970) and 21 years of cancer incidence data from the national cancer registry. Results The results from our analysis were in accordance with recognised risks in selected occupational groups. The estimated relative effects from tobacco and alcohol on cancer risk were largely in line with results from Nordic reports. For lung cancer, adjustment for tobacco implied relative changes in SIR between a decrease from 1.16 to 0.72 (Fishermen), and an increase from 0.47 to 0.95 (Forestry workers). Conclusions We consider the method useful for achieving less confounded estimates of cancer risk in large cohort studies with no available information on smoking and alcohol consumption. Electronic supplementary material The online version of this article (doi:10.1007/s10552-016-0847-x) contains supplementary material, which is available to authorized users.

Purpose Colorectal cancer mortality rates dropped by half in the past three decades, but these gains were accompanied by striking differences in colorectal cancer mortality by socioeconomic status (SES). Our research objective is to examine disparities in colorectal cancer mortality by SES, using a scientifically rigorous and reproducible approach with publicly available online tools, HD*Calc and NCI SES Quintiles. Methods All reported colorectal cancer deaths in the United States from 1980 to 2010 were categorized into NCI SES quintiles and assessed at the county level. Joinpoint was used to test for significant changes in trends. Absolute and relative concentration indices (CI) were computed with HD*Calc to graph change in disparity over time. Results Disparities by SES significantly declined until 1993–1995, and then increased until 2010, due to a mortality drop in populations living in high SES areas that exceeded the mortality drop in lower SES areas. HD*Calc results were consistent for both absolute and relative concentration indices. Inequality aversion parameter weights of 2, 4, 6 and 8 were compared to explore how much colorectal cancer mortality was concentrated in the poorest quintile compared to the richest quintile. Weights larger than 4 did not increase the slope of the disparities trend. Conclusions There is consistent evidence for a significant crossover in colorectal cancer disparity from 1980 to 2010. Trends in disparity can be accurately and readily summarized using the HD*Calc tool. The disparity trend, combined with published information on the timing of screening and treatment uptake, is concordant with the idea that introduction of medical screening and treatment leads to lower uptake in lower compared to higher SES populations and that differential uptake yields disparity in population mortality.

Purpose Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. Methods We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55–83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993–2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9–12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER−/PR−. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR. Results Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33–2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63–3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19–2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors. Conclusions There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1. Electronic supplementary material The online version of this article (doi:10.1007/s10552-016-0779-5) contains supplementary material, which is available to authorized users.

Purpose Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. Methods We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data. Endometrial tissue mRNA and protein levels were measured using quantitative real-time PCR and immunohistochemistry, respectively. Results In postmenopausal women, we observed higher levels of phosphorylated IGF-I/insulin receptor (pIGF1R/pIR) in diabetic versus non-diabetic women (p value =0.02), while women who reported regular nonsteroidal anti-inflammatory drug use versus no use had higher levels of insulin and progesterone receptors (both p values ≤0.03). We also noted differences in pIGF1R/pIR staining with OC use (postmenopausal women only), and the proportion of estrogen receptor-positive tissues varied by the number of live births and PTEN status (premenopausal only) (p values ≤0.04). Compared to premenopausal proliferative phase women, postmenopausal women exhibited lower mRNA levels of IGF1, but higher IGFBP1 and IGFBP3 expression (all p values ≤0.004), and higher protein levels of the receptors for estrogen, insulin, and IGF-I (all p values ≤0.02). Conversely, pIGF1R/pIR levels were higher in premenopausal proliferative phase versus postmenopausal endometrium (p value =0.01). Conclusions These results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis. Electronic supplementary material The online version of this article (doi:10.1007/s10552-016-0751-4) contains supplementary material, which is available to authorized users.

Purpose The relationship between obesity and prostate cancer (CaP) treatment failure is complex and may vary by patient- and neighborhood-level educational attainment. We evaluated whether patient- and neighborhood-level education is associated with the effect of obesity on biochemical recurrence. Methods Seven hundred and forty-six CaP cases were classified into four groups: Concordant Low–Low: less educated cases (

Purpose There are indications that a history of allergy may offer some protection against cancer. We studied the relation of three objectively determined allergy markers with cancer mortality and hospitalization risk. Methods Associations between three allergy markers (number of peripheral blood eosinophil counts, skin test positivity, and serum total IgE) with mortality and hospitalization from any type and four common types of cancer (lung, colorectal, prostate, and breast cancer) were assessed in the Vlagtwedde–Vlaardingen cohort (1965–1990), with follow-up of mortality until 31 December 2008. Hospitalization data were available since 1 January 1995. Results There were no significant associations between objective allergy markers and cancer mortality or hospitalization. We found several associations in specific subgroups. A higher number of eosinophils was associated with a decreased risk of colorectal cancer mortality in ever smokers HR (95 % CI) = 0.61 (0.45–0.83) and in males 0.59 (0.42–0.83); however, no overall association was observed 0.84 (0.64–1.09). Skin test positivity was associated with a decreased risk of any cancer mortality only among females 0.59 (0.38–0.91) and showed no overall association 0.83 (0.67–1.04). Serum total IgE levels were associated with an increased risk of lung cancer mortality among females 4.64 (1.04–20.70), but with a decreased risk of cancer hospitalization in ever smokers 0.77 (0.61–0.97) and males 0.72 (0.55–0.93); however, no overall associations were observed [mortality 0.99 (0.79–1.25), and hospitalization 0.86 (0.71–1.04)]. Conclusions We found no associations between objective allergy markers and cancer in the total population. However, skin test positivity and a high number of eosinophils were associated with a reduced risk to die of cancer in specific subgroups. Hence, it seems important to study specific subgroups defined by gender and smoking habits in order to identify allergy markers of predictive value for cancer mortality. Electronic supplementary material The online version of this article (doi:10.1007/s10552-014-0489-9) contains supplementary material, which is available to authorized users.

Purpose Prior studies suggest cigarette smoking is associated with 1.5- to twofold increased risk of colorectal adenomas and possibly a higher risk of serrated polyps. Further clarification of risk differences between adenomas and serrated polyps is needed with regard to co-occurrence and polyp location. Methods We conducted a combined analysis of conventional adenoma and serrated polyp occurrence using individual-level data from 2,915 patients participating in three colonoscopy-based clinical trials. All participants had ≥1 adenomas removed at baseline and were followed for up to 4 years. Smoking habits and other lifestyle factors were collected at baseline using questionnaires. We used generalized linear regression to estimate risk ratios and 95 % confidence intervals. Results Smokers were at slightly increased risk of adenomas compared to never smokers [current: RR 1.29 (95 % CI 1.11–1.49) and former: RR 1.18 (1.05–1.32)]. Smoking was associated with greater risk of serrated polyps [current: RR 2.01 (1.66–2.44); former: RR 1.42 (1.20–1.68)], particularly in the left colorectum. Associations between current smoking and occurrence of serrated polyps only [RR 2.33 (1.76–3.07)] and both adenomas and serrated polyps [RR 2.27 (1.68–3.06)] were more pronounced than for adenomas only [RR 1.31 (1.08–1.58)]. Results were similar for other smoking variables and did not differ by gender or for advanced adenomas. Conclusions Cigarette smoking has only a weak association with adenomas, but is associated with a significantly increased risk of serrated polyps, particularly in the left colorectum. Since a minority of left-sided serrated polyps is thought to have malignant potential, the role of smoking in initiation phases of carcinogenesis is uncertain.

The objective of this paper was to study cancer incidence, especially leukemia in children (15 years), in the vicinity of Finnish nuclear power plants (NPPs). We used three different approaches: ecological analysis at municipality level, residential cohorts defined from census data, and case-control analysis with individual residential histories. The standardized incidence ratio of childhood leukemia for the seven municipalities in the vicinity of NPPs was 1.0 (95% CI 0.6, 1.6) compared to the rest of Finland. The two cohorts defined by censuses of 1980 and 1990 gave rate ratios of 1.0 (95% CI 0.3, 2.6) and 0.9 (95% CI 0.2, 2.7), respectively, for childhood leukemia in the population residing within 15 km from the NPPs compared to the 15-50 km zone. The case-control analysis with 16 cases of childhood leukemia and 64 matched population-based controls gave an odds ratio for average distance between residence and NPP in the closest 5-9.9 km zone of 0.7 (95% CI 0.1, 10.4) compared toor =30 km zone. Our results do not indicate an increase in childhood leukemia and other cancers in the vicinity of Finnish NPPs though the small sample size limits the strength of conclusions. The conclusion was the same for adults.

Purpose For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. Methods Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. Results Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21–0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05–0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. Conclusions Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Purpose Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype. Methods The Marin Women’s Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry. Results A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = −0.31, 95 % CI −0.52, −0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95 % CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants. Conclusion These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes. Electronic supplementary material The online version of this article (doi:10.1007/s10552-014-0386-2) contains supplementary material, which is available to authorized users.

Background\ud \ud A campaign to increase the awareness of the signs and symptoms of colorectal cancer (CRC) and encourage self-presentation to a GP was piloted in two regions of England in 2011. Short-term data from the pilot evaluation on campaign cost and changes in GP attendances/referrals, CRC incidence, and CRC screening uptake were available. The objective was to estimate the effectiveness and cost-effectiveness of a CRC awareness campaign by using a mathematical model which extrapolates short-term outcomes to predict long-term impacts on cancer mortality, quality-adjusted life-years (QALYs), and costs.\ud \ud Methods\ud \ud A mathematical model representing England (aged 30+) for a lifetime horizon was developed. Long-term changes to cancer incidence, cancer stage distribution, cancer mortality, and QALYs were estimated. Costs were estimated incorporating costs associated with delivering the campaign, additional GP attendances, and changes in CRC treatment.\ud \ud Results\ud \ud Data from the pilot campaign suggested that the awareness campaign caused a 1-month 10 % increase in presentation rates. Based on this, the model predicted the campaign to cost £5.5 million, prevent 66 CRC deaths and gain 404 QALYs. The incremental cost-effectiveness ratio compared to “no campaign” was £13,496 per QALY. Results were sensitive to the magnitude and duration of the increase in presentation rates and to disease stage.\ud \ud Conclusions\ud \ud The effectiveness and cost-effectiveness of a cancer awareness campaign can be estimated based on short-term data. Such predictions will aid policy makers in prioritizing between cancer control strategies. Future cost-effectiveness studies would benefit from campaign evaluations reporting as follows: data completeness, duration of impact, impact on emergency presentations, and comparison with non-intervention regions.

Purpose Alcohol consumption is hypothesized to increase the risk of endometrial cancer by increasing circulating estrogen levels. This study sought to investigate the association between lifetime alcohol consumption and endometrial cancer risk. Methods We recruited 514 incident endometrial cancer cases and 962 frequency age-matched controls in this population-based case–control study in Alberta, Canada, from 2002 to 2006. Participants completed in-person interviews querying lifetime alcohol consumption and other relevant health and lifestyle factors. Participants reported the usual number of drinks of beer, wine, and liquor consumed; this information was compiled for each drinking pattern reported over the lifetime to estimate average lifetime exposure to alcohol. Results Lifetime average alcohol consumption was relatively low (median intake: 3.9 g/day for cases, 4.9 g/day for controls). Compared with lifetime abstainers, women consuming >2.68 and ≤8.04 g/day alcohol and >8.04 g/day alcohol on average over the lifetime showed 38 and 35 % lower risks of endometrial cancer, respectively (p trend = 0.023). In addition, average lifetime consumption of all types of alcohol was associated with decreased risks. There was no evidence for effect modification by body mass index, physical activity, menopausal status, and hormone replacement therapy use combined and effects did not differ by type of endometrial cancer (type I or II). Conclusion This study provides epidemiologic evidence for an inverse association between relatively modest lifetime average alcohol consumption (approximately 1/4 to 1/2 drink/day) and endometrial cancer risk. The direction of this relation is consistent with previous studies that examined similar levels of alcohol intake.

Purpose To determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Methods Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case–control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Cases (n = 316) were identified through provincial cancer registries and hospital records. Controls (n = 1,506) were frequency-matched to cases by age (±2 years) within each province and were identified through provincial health records, telephone listings, or voter lists. The Cochran–Armitage test was used to check for trends within pesticide classes. Results Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88, 95 % CI 0.92–3.87) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16, 95 % CI 1.02–9.29). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47, 95 % CI 1.06–5.75), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. When analyses excluded proxy respondents, OR estimates strengthened in some circumstances. Conclusions This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens. These associations should be further evaluated, specifically in relation to age at diagnosis.

Purpose Arsenic is a known human carcinogen and has been linked to adverse health outcomes, including cancer. However, the effects of arsenic exposure from food on health are still unknown. We researched to examine the association between arsenic exposure from food and incidence of cancer in a Japanese population. Methods We conducted a population-based prospective study in 90,378 Japanese men and women aged 45–74 years. Participants responded to a validated questionnaire that included 138 food items. We estimated dietary arsenic intake from 12 food groups (75 items) based on the questionnaire data. During 11 years of follow-up, 7,002 cancer cases were identified. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer were calculated by Cox proportional hazards modeling. Results Total arsenic and inorganic arsenic showed no association with the risk of total cancer in both men and women. Total arsenic and inorganic arsenic intake tended to be associated with an increased risk of lung cancer in men. In particular, these positive associations were strengthened in currently smoking men, with HRs (95 % CI) in the highest categories of arsenic and inorganic arsenic intake compared with the lowest of 1.29 (95 % CI = 1.03–1.61) and 1.36 (95 % CI = 1.09–1.70), respectively. We also detected an interaction between arsenic and inorganic arsenic intake and smoking status in men (pinteraction

Objectives Pre-clinical studies have shown that iron can be carcinogenic, but few population-based studies investigated the association between markers of the iron metabolism and risk of cancer while taking into account inflammation. We assessed the link between serum iron (SI), total-iron binding capacity (TIBC), and risk of cancer by levels of C-reactive protein (CRP) in a large population-based study (n = 220,642). Methods From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (>20 years old) with baseline measurements of serum SI, TIBC, and CRP. Multivariate Cox proportional hazards regression was carried out for standardized and quartile values of SI and TIBC. Similar analyses were performed for specific cancers (pancreatic, colon, liver, respiratory, kidney, prostate, stomach, and breast cancer). To avoid reverse causation, we excluded those with follow-up

Background Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk. Methods We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures. Results We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively. Conclusions Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants. Electronic supplementary material The online version of this article (doi:10.1007/s10552-012-9947-4) contains supplementary material, which is available to authorized users.

Background Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes. Methods We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995–2002. Results We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL. Conclusions These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis. Electronic supplementary material The online version of this article (doi:10.1007/s10552-011-9848-y) contains supplementary material, which is available to authorized users.

Background Few population-based epidemiological data are available on Merkel cell carcinoma (MCC), a rare lethal non-melanoma skin cancer. We analysed multiple-cause-of-death records to describe MCC mortality and trends and the association with other primary cancers. Methods We reviewed all 6,713,059 death certificates in Italy (1995–2006) to identify those mentioning MCC. We evaluated the association with other primary cancers by calculating the ratio of observed to expected deaths, using a standardized mortality ratio (SMR)-like analysis. We also evaluated the geographic distribution of deaths. Results We identified 351 death certificates with the mention of MCC. The age-adjusted mortality was 0.031/100,000, with a significant trend of increase and a slight north–south gradient. There was a significant deficit for solid cancers (SMR = 0.15) and a non-significant excess for lymphohematopoietic malignancies (SMR = 1.62). There were significant excesses for chronic lymphocytic leukemia (SMR = 4.07) and Waldenström’s macroglobulinemia (SMR = 27.2) and a non-significant excess for chronic myeloid leukemia (SMR = 5.12). Conclusions The increase in MCC mortality reflects the incidence trend in the literature. The association with chronic lymphocytic leukemia confirms the importance of immunologic factors in MCC. Regarding Waldenström’s macroglobulinemia, an association with MCC has never been reported.

Objective To identify factors that mediate or moderate the effects of exercise on postmenopausal sex hormone concentrations. Methods Postmenopausal women were randomized to 12 months of aerobic exercise for 200 min/week (n = 160) or to a control group (n = 160). Intention-to-treat analyses were performed using general linear models with sex hormone concentrations at 6 and 12 months as the outcome. Mediation by adiposity and insulin was investigated by examining changes in effect estimates after adjustment for changes in these factors over 12 months. Moderation was studied as the interaction between group assignment and eight baseline characteristics. Results Intervention effects on sex hormone–binding globulin (SHBG) and estradiol changes were attenuated with adjustment for change in overall body fat, while there was less attenuation adjusting for intra-abdominal fat change. Intervention effects on SHBG levels were unaffected by adjustment for insulin change. Significant interactions were identified between treatment and physical fitness (for SHBG and testosterone) and age (for testosterone), implying subgroup differences in intervention effect. Conclusions Our data suggest that overall fat loss partially mediated exercise-induced changes in estradiol and SHBG concentrations. No previous RCT in postmenopausal women has studied moderators of exercise-induced sex hormone changes; therefore, future studies are needed to corroborate our results.

Background We examine whether the lung cancer risk due to smoking has increased over time. Methods Lung cancer risk equations based on prospective mortality data collected from 1960 to 1972 were applied to 5-year birth-cohort-specific estimates of smoking behaviors among white males to estimate lung cancer mortality rates for U.S. white males from 1960 to 2000. These estimated rates were compared to U.S. white male mortality rates for the same birth cohorts. Results Observed birth-cohort-specific U.S. lung cancer mortality rates are substantially higher than those expected from changes in smoking behaviors, and the proportional difference increases with advancing calendar year. This trend persisted even when the duration term was increased in the risk equation. However, adjusting for changes in cigarette design over time by adding a term for the duration of smoking after 1972 resulted in the predicted rates closely approximating the observed U.S. mortality rates. Conclusion Lung cancer risk estimates observed during the 1960s under predict current lung cancer mortality rates in U.S. white males. Adjustment for the duration of smoking after 1972 results in estimates that reasonably approximate the observed U.S. lung cancer mortality, suggesting that lung cancer risks from smoking are increasing in the United States coincident with changes in cigarette design.

Objective To investigate the association between selenium and the risk of Barrett’s esophagus (BE), the precursor lesion of esophageal adenocarcinoma. Methods Data from the prospective Netherlands Cohort Study were used. This cohort study was initiated in 1986, when 120,852 subjects aged 55–69 years completed a questionnaire on dietary habits and lifestyle, and provided toenail clippings for the determination of baseline selenium status. After 16.3 years of follow-up, 253 BE cases (identified through linkage with the nationwide Dutch pathology registry) and 2,039 subcohort members were available for case–cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR). Results The multivariable-adjusted RR for the highest versus the lowest quartile of toenail selenium was 1.06 (95% CI 0.71–1.57). No dose–response trend was seen (p trend = 0.99). No association was found in subgroups defined by sex, smoking status, body mass index (BMI), or intake of antioxidants. For BE cases that later progressed to high-grade dysplasia or adenocarcinoma, the RR for a selenium level above the median vs. below the median was 0.64 (95% CI 0.24–1.76). Conclusions In this large prospective cohort study, we found no evidence of an association between selenium and risk of BE. Electronic supplementary material The online version of this article (doi:10.1007/s10552-010-9651-1) contains supplementary material, which is available to authorized users.

Background: We investigated the association between hypertension, antihypertensive (AH) medication use, and breast cancer in a large prospective study, the California Teachers Study (CTS). Methods: Information on history of hypertension and lifetime regular use of AH medications was collected from 114,549 women in 1995-1996. Among them, 4,151 invasive breast cancers were diagnosed between 1995 and 2006. Additional information on AH use was collected from 73,742 women in 2000-2001, and 1,714 of these women were subsequently diagnosed with breast cancer. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for breast cancer. Results: Use of AH medication for ≥5 years, when compared with no use, was associated with a modest increased risk of invasive breast cancer (RR = 1.18, 95%CI 1.02-1.36). This increased risk appeared to be confined to estrogen receptor (ER)-positive tumors (RR = 1.21, 95%CI 1.03-1.43) and pre-/peri-menopausal women (RR = 1.58, 95%CI 1.11-2.25). Conclusions: Increased risk of invasive breast cancer was observed for long-term (≥5 years) AH use, and this appeared to be confined to ER + breast cancer and younger women. © 2010 The Author(s).

Objective Very few studies have simultaneously examined incidence of the leading cancers in relation to socioeconomic status (SES) and race/ethnicity in populations including Hispanics and Asians. This study aims to describe SES disparity in cancer incidence within each of four major racial/ethnic groups (non-Hispanic white, black, Hispanic, and Asian/Pacific Islander) for five major cancer sites, including female breast cancer, colorectal cancer, cervical cancer, lung cancer, and prostate cancer. Methods Invasive cancers of the five major sites diagnosed from 1998 to 2002 (n = 376,158) in California were included in the study. Composite area-based SES measures were used to quantify SES level and to calculate cancer incidence rates stratified by SES. Relative index of inequality (RII) was generated to measure SES gradient of cancer incidence within each racial/ethnic group. Results Significant variations were detected in SES disparities across the racial/ethnic groups for all five major cancer sites. Female breast cancer and prostate cancer incidence increased with increased SES in all groups, with the trend strongest among Hispanics. Incidence of cervical cancer increased with decreased SES, with the largest gradient among non-Hispanic white women. Lung cancer incidence increased with decreased SES with the exception of Hispanic men and women, for whom SES gradient was in the opposite direction. For colorectal cancer, higher incidence was associated with lower SES in non-Hispanic whites but with higher SES in Hispanics and Asian/Pacific Islander women. Conclusions Examining SES disparity stratified by race/ethnicity enhances our understanding of the complex relationships between cancer incidence, SES, and race/ethnicity.

Objective Multiple studies have shown clear evidence of vitamin D’s anti-tumor effects on prostate cancer cells in laboratory experiments, but the evidence has not been consistent in humans. We sought to examine the association between vitamin D and prostate cancer risk in a cohort of older men. Methods We conducted a prospective case-cohort study nested within the multicenter Osteoporotic Fractures in Men (MrOS) study. Baseline serum 25-OH vitamin D was measured in a randomly selected sub-cohort of 1,433 men ≥65 years old without a history of prostate cancer and from all participants with an incident diagnosis of prostate cancer (n = 297). Cox proportional hazards models were used to evaluate the associations between quartiles of total 25-OH vitamin D and incident prostate cancer, as well as Gleason score. Results In comparison with the lowest quartile of 25-OH vitamin D, the hazard ratio for the highest quartile of 25-OH vitamin D was 1.22 (CI 0.50–1.72, p = 0.25), no trend across quartiles (p = 0.94) or association with Gleason score was observed. Adjustment for covariates did not alter the results. Conclusions In this prospective cohort of older men, we found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer.

Objective To examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women. Methods A cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression. Results Among 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4 500/mm3. HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels

To determine the relationship between 25(OH) vitamin D levels and non-melanoma skin cancer (NMSC), we performed a nested case–control study in ambulatory, elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study. Health habit and medical history, including self-reported history of NMSC were recorded and 25(OH)D levels were measured on serum collected at baseline from a random sample of Caucasian MrOS subjects. Mean age (73 ± 5), BMI, daily vitamin D and calcium intake were similar in the men with (n = 178) and without NMSC (n = 930), but higher levels of 25(OH)D were associated with a decreased risk of having a history of NMSC (P trend = 0.04). Men in the highest quintile of 25(OH)D (>30 ng/mL) had 47% lower odds of NMSC (95% CI: 0.30–0.93, p = 0.026) compared to those in the lowest quintile. Our results suggest that a diagnosis of NMSC is not a surrogate for adequate 25(OH)D levels or increased UV exposure, and high 25(OH)D levels may be associated with a reduced risk of NMSC.

Objective The association between duration of pancreatitis and pancreatic cancer has not been well characterized in large population-based studies. We conducted detailed analyses to determine the association between pancreatitis onset and pancreatic cancer risk. Methods Data from two case–control studies of pancreatic cancer (n = 4515) in the San Francisco Bay Area and the M.D. Anderson Cancer Center were pooled for analysis (1,663 cases, 2,852 frequency-matched controls). Adjusted odds ratios (OR) were estimated using a random-effects model. Results In the pooled multivariable model, history of pancreatitis was associated with a 7.2-fold increased risk estimate for pancreatic cancer [95% confidence interval (CI): 4.0, 13]. The risk estimate was nearly 10-fold in participants aged 10 years (OR = 1.8, 95% CI: 0.7, 4.5, ptrend

Objective To understand area-based sociodemographics, physician and medical practice characteristics, and community indicators associated with mammography use in Los Angeles County. An earlier multi-level analysis by Gumpertz et al. found that distance to the nearest mammography facility helped explain the higher proportion of Latinas diagnosed with late stage breast cancer compared with non-Latina Whites in Los Angeles County. Our study examined whether Latinas also have lower rates of mammography use. Methods We used a multi-level spatial modeling approach to examine individual and community level associations with mammography use among a diverse group of women aged 40–84 years in Los Angeles County. To build our multi-level spatial data set, we integrated five data sources: (1) 2001 California Health Interview Survey (CHIS) data, (2) 2001 Food and Drug Administration (FDA) certified mammography facility data, (3) 2003 LA Transit Authority data, (4) 2000 US Decennial Census data, and (5) 2001 Community Tracking Study (CTS) Physician’s Survey data. Results Our study confirmed for Los Angeles County many associations for mammography use found in other locations. An unexpected finding was that women with limited English proficiency (predominantly Latina) were significantly more likely to have had a recent mammogram than English-proficient women. We also found that, after controlling for other factors, mammography use was higher in neighborhoods with a greater density of mammography facilities. Conclusion Women with limited English proficiency were especially likely to report recent mammography in Los Angeles. This unexpected finding suggests that the intensive Spanish-language outreach program conducted by the Every Woman Counts (EWC) Program in low-income Latina communities in Los Angeles has been effective. Our study highlights the success of this targeted community-based outreach conducted between 1999 and 2001. These are the same populations that Gumpertz et al. identified as needing intervention. It would be useful to conduct another study of late-stage diagnosis in Los Angeles County to ascertain whether increased rates of mammography have also led to less late-stage diagnosis among Latinas in the neighborhoods where they are concentrated in Los Angeles.

OBJECTIVE: In California, leukemia represents ~35, 5, and 2% of all cancers in children (aged 0-14), adolescents (15-29), and young adults (30-39), respectively. Poorer survival has been previously noted in individuals residing in lower socioeconomic status (SES) neighborhoods. We explored the relationship between SES and survival as modified by age and race/ethnicity using data from the California Cancer Registry. METHODS: A total of 7,688 incident cases of first primary leukemia diagnosed during 1996-2005 in individuals aged 0-39 at diagnosis were included in this study. Univariate analyses of overall survival were conducted using the Kaplan-Meier method and multivariate survival analyses were performed using Cox proportional hazard regression to estimate hazard ratios. RESULTS: Multivariate analyses showed that overall survival and lymphoid cancer-specific survival was reduced in those individuals aged 15-39 compared to children aged 0-14. Although shorter survival was observed in non-whites, an association between lower-SES neighborhood and shorter survival was significant only for non-Hispanic whites (NHWs) (p value for trend

Background Human papilloma virus (HPV) prevalence studies performed in different regions and population groups across Canada would inform public health decisions regarding implementation of anti-HPV vaccines. Methods A total of 8,700 liquid-based specimens from 8,660 women aged 13–86 from throughout British Columbia were collected. DNA was isolated from 4,980 of these samples and assessed for HPV prevalence and type distribution. HPV was detected by PCR analysis using tagged GP5+/6+ consensus primers to amplify the L1 region of HPV; typing was done by bi-directional sequencing of PCR products. Results Overall HPV prevalence was 16.8% (age adjusted 15.5%). Prevalence of high-risk HPV was 13.9, and 10.7% of samples contained HPV16. HPV prevalence was highest in the youngest group of women (