Cigarette smoking and risk of glioma: a prospective cohort study

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. N-nitroso compounds are known carcinogens, which are found in cigarette smoke and can induce gliomas in rats. On this basis, it has been hypothesized that cigarette smoking may be associated with an increased risk of glioma. We investigated the association between cigarette smoking and glioma risk in the National Breast Screening Study, which included 89,835 Canadian women aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between cigarette smoking and risk of glioma. During a mean of 16.4 years of follow-up, we observed 120 incident glioma cases. Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97-2.34), while current smokers did not appear to have an increase in risk. When the association with former smokers was further examined by years since quitting, women who had quit smoking >10 years before baseline were at a decreased risk of glioma compared with women who had quit within the 10 years prior to baseline (HR = 0.55, 95% CI = 0.29-1.07), indicating that the association between former smokers and glioma may be driven by women, who recently quit smoking. Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack-years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest. The present study provides some support for a positive association between cigarette smoking and risk of glioma.     

Hormonal and reproductive factors and risk of glioma: a prospective cohort study

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. Given the lower incidence rate of glioma in women than in men, it has been hypothesized that reproductive and hormonal factors may be involved in the etiology of glioma. We conducted a secondary analysis of data from the National Breast Screening Study, which included 89,835 Canadian women, aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between hormonal and reproductive factors and risk of glioma. During a mean of 16.4 years of follow-up, we observed 120 incident glioma cases. Compared with women with a relatively early age at menarche (< or =12 years), women who were 13-14 years of age at menarche had a 64% increased risk of glioma (95% CI = 1.01-2.65), and women who were older than 14 years of age at menarche had a 66% increased risk of glioma (95% CI = 0.86-3.20, p(trend) = 0.06). Age at first live birth, parity, menopausal status, use of oral contraceptive and use of hormone replacement therapy were not associated with altered glioma risk in our study population. Additional prospective studies are needed to confirm our findings.     

Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997–2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32–120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64–1.43), 1.34 (0.96–1.86), and 1.06 (0.88–1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08–2.28] and 1.31 [1.03–1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15–3.00]) than in males (aHR = 1.16 [0.74–1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5–10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.     

Evaluating the safety of perioperative dexamethasone treatment: A retrospective analysis of a single center pediatric low-grade glioma cohort

In addition to surgical management, corticosteroids have proven to be beneficial in the management of acute symptoms related to CNS tumors, and have been widely used for many decades, with dexamethasone (DM) representing the most commonly used agent. However, lately published in vitro data possibly indicates a DM-induced suppression of oncogene-induced senescence (OIS) in a preclinical pediatric low-grade glioma (pLGG) model, which, alongside data associating perioperative DM treatment with reduced event-free survival in adult glioma, raises questions concerning the safety of DM treatment in pLGG. A total of 172 patients with pLGG were retrospectively analyzed concerning the impact of perioperative DM application on postoperative short- and long-term tumor growth velocity and progression-free survival (PFS). Three-dimensional volumetric analyses of sequential MRI follow-up examinations were used for assessment of tumor growth behavior. Mean follow-up period accounted for 60.1 months. Sixty-five patients (45%) were perioperatively treated with DM in commonly used doses. Five-year PFS accounted for 93% following gross-total resection (GTR) and 57% post incomplete resection (IR). Comparison of short- and long-term postoperative tumor growth rates in patients with vs without perioperative DM application showed no significant difference (short-term: 0.022 vs 0.023 cm³/month, respectively; long-term: 0.019 vs 0.023 cm³/month, respectively). Comparison of PFS post IR (5-year-PFS: 65% vs 55%, respectively; 10-year-PFS: 52% vs 53%, respectively) and GTR (5- and 10-years-PFS: 91% vs 92%, respectively) likewise showed similarity. This data emphasizes the safety of perioperative DM application in pLGG, adding further evidence for decision making and requested future guidelines.     

Radiotherapy management of patients diagnosed with glioma in Victoria (1998–2000): A retrospective cohort study

This study aimed to describe the radiotherapy (RT) management and subsequent outcome in a cohort of patients with newly diagnosed glioma. Treatment details were obtained via a questionnaire completed by neurosurgeons, radiation and medical oncologists who treated patients diagnosed with glioma in Victoria during 1998–2000. Patients were identified by using the population‐based Victorian Cancer Registry. Over the study period, data on 828 patients were obtained, of whom 612 (74%) were referred for consideration of RT. Radiotherapy was given to 496 patients as part of their initial treatment and to an additional 10 patients at the time of tumour recurrence or progression. The median age was 72 (16–85) years. Median overall survival (OS) was 9.2 (standard error (SE) 0.6) months for the entire group. Median OS was 29.1 (SE 8.0) and 7.4 (SE 0.4) months for all patients with histological confirmation of World Health Organization Grades III (anaplastic astrocytoma) and IV (glioblastoma multiforme) histology, respectively. A total of 47 different RT dose fractionation schedules were identified. This is the largest survey detailing management of glioma with RT, published to date. A marked variation in dose fractionation schemes was evident. While current best practice involves the use of chemotherapy in conjunction with RT for glioblastoma multiforme, advances in patient care may be undermined by this variation in the use of RT. Clinical trials relevant to an ageing population and evidence‐based national clinical guidelines are required to define best practice.     

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970-1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7-4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8-63.2), lip cancer (SIR 53.3; 95% CI 38.0-72.5) and of non-Hodgkin's lymphoma (NHL) (SIR 6.0; 95% CI 4.4-8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3-16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.     

Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study

Background:

This study examined the risk of cancer in patients with Hashimoto''s thyroiditis (HT).

Methods:

The Taiwanese National Health Insurance Research Database (NHIRD) was used to identify 1521 newly diagnosed HT patients from 1998–2010, and 6084 frequency-matched non-HT patients. The risk of developing cancer for HT patients was measured using the Cox proportional hazard model.

Results:

The incidence of developing cancer in the HT cohort was 5.07 per 1000 person-years, which was 1.68-fold higher than that in the comparison cohort (P<0.001). Compared with patients aged 20–34 years, patients in older age groups had a higher risk of developing cancer (35–55 years: hazard ratio (HR)=5.96; >55 years: HR=9.66). After adjusting for sex, age, and comorbidities, the HT cohort had HRs of 4.76 and 11.8 for developing colorectal cancer and thyroid cancer, respectively, compared with non-HT cohort. Furthermore, the HT cohort to non-HT cohort incidence rate ratio (IRR) of thyroid cancer was higher in the first 3 years (48.4, 95% confidence interval (CI)=35.0–66.3), with an adjusted HR of 49.4 (95% CI=6.39–382.4).

Conclusion:

Hashimoto''s thyroiditis patients have a higher risk of thyroid cancer and colorectal cancer. The thyroid cancer prevention effort should start soon after HT is diagnosed, while being cautious of colorectal cancer increases with time.     

Neurocognitive changes after awake surgery in glioma patients: a retrospective cohort study

Journal of Neuro-Oncology - Deficits in neurocognitive functioning (NCF) frequently occur in glioma patients. Both treatment and the tumor itself contribute to these deficits. In order to minimize...     

Hypertension as a risk factor for glioma? Evidence from a population-based study of comorbidity in glioma patients.

BACKGROUND: Little is known about the aetiology of glioma. Research is often hampered by the low incidence and high mortality of the disease. Concomitant diseases in glioma patients may indicate possible aetiological pathways. We therefore studied comorbidity in glioma patients. PATIENTS AND METHODS: We performed a case-control study using population-based data from the Eindhoven Cancer Registry. We compared prevalences of concomitant diseases in 510 glioma patients with two reference cancer populations from the same registry. RESULTS: Compared with all other cancer patients, a significantly higher prevalence of hypertension was found in glioma patients for age categories 60-74 years [odds ratio (OR) 1.37; 95% confidence interval (CI) 1.02-1.84] and 75+ years (OR 2.37; 95% CI 1.34-4.21). The association was most pronounced in elderly men and in astrocytic glioma, with a maximum in age category 75+ years (OR 5.86; 95% CI 2.20-15.7). The prevalence of cerebrovascular disease was higher in glioma patients >45 years old (OR 1.67; 95% CI 1.12-2.47), whereas the prevalence of other cancers was lower (OR 0.64; 95% CI 0.48-0.87). No consistent associations were detected for several other concomitant diseases. CONCLUSIONS: Our data suggest an association between hypertension and glioma, although questions remain about causality and the possible mechanisms. We hypothesise that this association is mediated through potentially neurocarcinogenic effects of antihypertensive medication.     

Immune-related conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans

Background:

Case–control studies have reported an inverse association between self-reported history of allergy and risk of glioma, but cohort data are limited. Our objectives were to evaluate the associations of major groups of medically diagnosed immune-related conditions (allergy/atopy, autoimmune disease, diabetes, infectious/inflammatory disease) and to explore associations with specific conditions in relation to subsequent diagnosis of brain cancer in a large cohort study.

Methods:

We used hospital discharge records for a cohort of 4.5 million male US veterans, of whom 4383 developed primary brain cancer. Rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using time-dependent Poisson regression.

Results:

We found a significant trend of decreasing RRs for brain cancer with longer duration of allergy/atopy (P=0.02), but not for other conditions studied. Rate ratios of brain cancer for allergy/atopy and diabetes with duration of 10 or more years were 0.60 (95% CI: 0.43, 0.83) and 0.75 (95% CI: 0.62, 0.93), respectively. Several associations with specific conditions were found, but these did not withstand correction for multiple comparisons.

Conclusions:

This study lends some support to an inverse association between allergy/atopy and diabetes of long duration and brain cancer risk, but prospective studies with biological samples are needed to uncover the underlying biological mechanisms.     

Association between leukocyte telomere length and glioma risk: a case-control study

Background

Compelling epidemiological evidence indicates that alterations of telomere length are associated with risks of many malignancies in a tumor-specific manner, such as lung cancer, breast cancer, and non-Hodgkin''s lymphoma. However, the association between leukocyte telomere length and glioma risk has not been investigated.

Methods

Relative telomere length (RTL) of peripheral blood leukocytes from 467 glioma patients and 467 healthy controls, matched by age and sex, was measured using the real-time PCR-based method in a case-control study. An unconditional multivariate logistic regression model was applied to estimate the association between RTL and glioma risk.

Results

Glioma patients showed notably longer RTL than controls (median, 0.555 vs 0.444; P > .04). RTL was negatively correlated with age in both cases (ρ = −0.430; P < .001) and controls (ρ = −0.388; P < .001). After adjusting for age, sex, smoking status and family history of cancer, multivariate logistic regression analysis showed that there was a U-shaped association between RTL and glioma risk (P for nonlinearity <.001). Compared with individuals in the second tertile of RTL, the odds ratios (95% CI) for participants in the first and third tertiles were 2.16 (range, 1.52–3.09) and 3.51 (range, 2.45–5.00), respectively. Stratified analysis showed that the association between RTL and glioma risk was not modulated by major host characteristics.

Conclusions

Our study demonstrates for the first time that either shorter or longer RTL in peripheral blood leukocytes is associated with increased glioma risk, which warrants further investigation in the future.     

Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark

Polymyositis and dermatomyositis (PM/DM) have been associated with cancer, although the long-term risks are poorly understood. To evaluate the risk of cancer by time periods subsequent to PM/DM diagnosis, a cohort of 539 patients hospitalized with PM/DM in Denmark between 1977 and 1989 was identified from the Danish Central Hospital Discharge Register. Cancer incidence among cohort members was ascertained by linkage to the Danish Cancer Registry using a unique personal-identification number. The overall cancer risk was elevated significantly among patients with DM (standardized incidence ratio [SIR]=3.8, 95 percent confidence interval [CI]=2.6–5.4) and to a lesser extent PM (SIR=1.7, CI=1.1–2.4). Significant excesses were observed for cancers of lung, ovary, and lymphatic and hematopoietic system. However, the excess cancer incidence declined steadily with increasing years since initial diagnosis of PM/DM. The cancer risk was increased about sixfold (SIR=5.9, CI=3.8–8.7) during the first year, but was lower during the second year (SIR=2.5, CI=1.1–4.8), with no significant excesses in subsequent years of follow-up. These findings confirm that PM/DM may occur as a paraneoplastic syndrome that calls for steps aimed at early cancer detection and treatment. Among long-term survivors of PM/DM, however, there is little evidence to warrant extensive preventive and screening measures beyond those recommended for the general population.Drs Chow, McLaughlin, and Fraumeni, and Ms Gridley are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD, USA. Dr McLaughlin is currently with the International Epidemiology Institute, Rockville, MD. Ms Mellemkjær and Dr Olsen are with the Division for Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. Address correspondence to Dr Chow, National Cancer Institute 6130 Executive Blvd, EPN/415, Rockville, MD 20852, USA.     

Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan

Background

The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan.

Methods

A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis.

Results

One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9–1.4) at 10 years and 2.6 % (95 % CI 2.1–3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-year survivors (n = 5,387), confirmed these low incidence rates. The SIR of secondary cancers was 12.1 (95 % CI 10.1–14.4). In the Cox analysis, the hazard ratios for secondary cancers were 3.81 (95 % CI 1.53–9.47) for retinoblastoma, 2.78 (95 % CI 1.44–5.38) for bone/soft tissue sarcomas, and 1.81 (95 % CI 1.16–2.83) for allogeneic stem cell transplantation.

Conclusions

The cumulative incidence of secondary cancers in children in Japan was not high; however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers.

     

乳腺癌相关淋巴水肿发病情况及危险因素回顾队列研究

目的 了解国内乳腺癌相关淋巴水肿的发病情况,并分析其相关的危险因素。方法对281例接受手术治疗的初治乳腺癌患者的临床资料和BCRL的发病情况进行回顾分析,采用Norman问卷和周径测量法对BCRL的发病情况进行评估,并应用χ²检验和二分类Logistic回归分析法对淋巴水肿发生的危险因素进行因素分析。结果 整组患者Norman问卷和周径测量两种诊断方法的BCRL发病率分别为31.7%和27.0%。多因素分析发现术后接受放疗(HR=2.87,P=0.042)、术前高体重指数≥24 kg/m²(HR=2.54,P=0.011)、腋窝淋巴结清扫范围大(HR=1.97,P=0.037)、腋淋巴结检测数目多(HR=1.06,P=0.023)都会增加BCRL发病风险。另外,合并高血压患者的BCRL发生风险是血压正常患者的1.74倍(P=0.044)。结论 BCRL仍有较高发病率,但大多数患者为轻度水肿。术后放疗、腋窝淋巴结清扫范围大、腋淋巴结检测数目多、术前高体重指数及合并高血压是发生BCRL的危险因素。