Effects of antihistamine and anti-inflammatory medication use on risk of specific glioma histologies

Several studies have shown a decrease in glioma risk associated with a personal history of allergic conditions and the medications used to treat the symptoms. However, few studies have been able to examine risk within histological subgroups of glioma. Case-control data from M. D. Anderson Cancer Center and University of California, San Francisco were pooled to conduct the analysis stratified by histological subtype. A risk prediction model considering inflammation-related variables and antihistamine use was built using logistic regression. Of the subtypes examined, long-term antihistamine use was associated with increased risk of anaplastic gliomas, especially when length of use was considered in conjunction with history of asthma or allergy. Anaplastic cases with no history of asthma or allergy were 2.94 times more likely than controls to report antihistamine use for 10 years or more; whereas anaplastic cases with a history of asthma or allergy were 2.34 times more likely than controls to report antihistamine use for 10 years or more. Furthermore, anti-inflammatory medication use was associated with a protective effect against glioblastoma (OR = 0.80; 95% CI: 0.65, 0.99), especially among individuals with no history of asthma or allergies. No statistically significant effects of anti-inflammatory drugs or antihistamines were evident for the other histological subtypes. Thus, modulation of the immune system by the use of common drugs, such as antihistamines or nonsteroidal anti-inflammatory drugs, may contribute to the development of certain types of brain tumors.     

Non-steroidal anti-inflammatory drug use and risk of adult leukemia.

Epidemiological studies have suggested that regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of some types of malignancy. Leukemia incidence and self-reported aspirin, as well as other NSAID use, was examined in a prospective cohort of >28,000 postmenopausal women. Eighty-one incident leukemia cases occurred during the period 1993-2000. The multivariate-adjusted relative risk of leukemia was 0.45 (95% confidence interval: 0.27-0.75) for women who reported using aspirin two or more times per week compared with women who reported no use. Similar inverse associations were observed for the two subtypes of leukemia analyzed. In contrast, for women who reported using nonaspirin NSAIDs, the multivariate-adjusted relative risk of leukemia was 1.31 (95% confidence interval: 0.77-2.22). Analyses that excluded cases diagnosed before 1995 did not notably alter results. To our knowledge, this is the first prospective study to examine the association between NSAID use and incident adult leukemia. Although preliminary, the notable differences observed in leukemia risk between aspirin and nonaspirin NSAID use warrant further investigation.     

Single-nucleotide polymorphisms of allergy-related genes and risk of adult glioma

Previous studies have shown an inverse association between allergies and glioma risk; however, results for associations between single nucleotide polymorphisms (SNPs) of allergy-related genes and glioma risk have been inconsistent and restricted to a small number of SNPs. The objective of this study was to examine the association between 166 SNPs of 21 allergy-related genes and glioma risk in a nested case–control study of participants from three large US prospective cohort studies. Blood collection took place between 1982 and 1994 among the 562 included Caucasian participants (143 cases and 419 matched controls) prior to case diagnosis. Custom Illumina assay chips were used for genotyping. Logistic regression analyses, controlling for age and study cohort, were used to determine associations between each SNP and glioma risk. Statistically significant associations were found between rs2494262 and rs2427824 of the FCER1A gene, which encodes the alpha chain of the high affinity immunoglobulin E receptor, and glioma risk (nominal trend p values 0.01 and 0.03, respectively). Significant associations were also found between SNPs in IL10, ADAM33, NOS1 and IL4R and glioma risk. However, our analyses were not corrected for multiple comparisons and need to be interpreted with caution. Our findings with FCER1A SNPs provide further support for the link between allergies and risk of glioma.     

Nonsteroidal anti-inflammatory drug use and breast cancer risk.

Findings from previous epidemiological studies are inconclusive, though they suggest nonsteroidal anti-inflammatory drug (NSAID) use is associated with a reduction in breast cancer risk. In addition, animal studies report that NSAIDs inhibit mammary tumor development. The association between NSAID use and breast cancer risk was evaluated using a case-control study design. Cases were a random sample of women diagnosed with a first primary cancer of the breast, aged 25-74 years, identified through the Ontario Cancer Registry, and diagnosed between July 1996 and September 1998. Controls were an age-matched random sample of the female population of Ontario. Cases (n = 3133) and controls (n = 3062) completed a mailed questionnaire with information on their past use of NSAID and other medications, as well as many risk factors thought to be associated with breast cancer. Multivariate logistic regression analysis was used to obtain adjusted odds ratio (OR) estimates. Use of any NSAID medication (daily use for > or =2 months) was found to be associated with a significant 24% reduction in breast cancer risk (OR = 0.76; 95% confidence interval: 0.66, 0.88). The reduced risk was strongest for use lasting > 8 years, compared with nonusers (OR = 0.68; 95% confidence interval: 0.54, 0.86). No marked trends were observed for time since first use or last use or age at first use. Our results suggest a reduction in breast cancer risk associated with any regular NSAID use. NSAID use is a modifiable factor, and any protective effect attributed to its use could be of great public health importance.     

Long-term survival in adult hemispheric glioma: Prognostic factors and quality of outcome

Between 1983 and 1985 111 patients with hemispheric gliomas were treated with whole brain irradiation in the Department of Clinical Oncology in Edinburgh. Of these, 52 patients were treated with mixed photons and neutrons and 51 patients with photons only. The 5-year actuarial survival is 6.1%. Age and tumour grade were confirmed as significant prognostic factors (P < 0.001). Assessment of all six adult survivors forms the basis of the morbidity report. All survivors had a degree of ataxia, spasticity and most of them showed radiological evidence of brain damage. Psychometric assessment confirmed impairment of cognitive function in all patients, as well as disruption of the socioeconomic units surrounding them. This could have been partially relieved if support was available.     

Occupation and the risk of adult glioma in the United States

Objective: Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. Methods: Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. Results: Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. Conclusions: This is our first analysis of occupation and will guide future exposure-specific assessments.     

Single-nucleotide polymorphisms in selected cytokine genes and risk of adult glioma

A role of immunological factors in glioma etiology is suggested by reports of an inverse relationship with history of allergy or autoimmune disease. To test whether single-nucleotide polymorphisms (SNPs) in cytokine genes were related to risk of adult glioma, we genotyped 11 SNPs in seven cytokine genes within a hospital-based study conducted by the National Cancer Institute and an independent, population-based study by the National Institute for Occupational Safety and Health (overall 756 cases and 1190 controls with blood samples). The IL4 (rs2243248, -1098T>G) and IL6 (rs1800795, -174G>C) polymorphisms were significantly associated with risk of glioma in the pooled analysis (P trend = 0.006 and 0.04, respectively), although these became attenuated after controlling for the false discovery rate (P trend = 0.07 and 0.22, respectively). Our results underscore the importance of pooled analyses in genetic association studies and suggest that SNPs in cytokine genes may influence susceptibility to glioma.     

Parental medication use and risk of childhood acute lymphoblastic leukemia

BACKGROUND: Few studies have examined the risk of childhood acute lymphoblastic leukemia (ALL) associated with parental medication use. As part of a large case-control study conducted by the Children's Cancer Group, we evaluated the association between maternal and paternal medication use and the risk of ALL in offspring. METHODS: Information on selected medication use in the year before and during the index pregnancy was obtained by telephone interview. Participants included 1842 children of 14 years or younger with newly diagnosed and immunophenotypically defined ALL and 1986 individually matched controls. Data were analyzed using logistic regression models and stratified by immunophenotypes of ALL and age at diagnosis of cases. RESULTS: After adjusting for potential confounders and other medication use, we found that maternal use of vitamins (odds ratio [OR] = 0.7, 99% confidence interval [CI]: 0.5-1.0) and iron supplements (OR = 0.8, 99% CI: 0.7-1.0) only during the index pregnancy was associated with a decreased risk of ALL. Parental use of amphetamines or diet pills and mind-altering drugs before and during the index pregnancy was related to an increased risk of childhood ALL, particularly among children where both parents reported using these drugs (OR = 2.8, 99% CI: 0.5-15.6 for amphetamines or diet pills, OR = 1.8, 99% CI: 1.1-3.0 for mind-altering drugs). Stratified analyses showed that maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with infant ALL, whereas patterns of association between childhood ALL and parental medication use did not influence markedly the immunophenotypic subgroup of ALL. CONCLUSIONS: The findings of this study suggest that certain parental medication use immediately before and during the index pregnancy may influence risk of ALL in offspring.     

Colorectal cancer risk in relation to antidepressant medication use

Laboratory studies suggest that antidepressants affect the risk of some cancers, including colorectal cancer. To investigate whether selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are associated with colorectal cancer risk, we conducted a case‐control study among enrollees of an integrated healthcare delivery system in Washington State. Cases were first diagnosed with invasive colorectal cancer between 2000 and 2003; controls were randomly selected from Group Health enrollees and matched to cases on age, sex and length of enrollment before diagnosis/reference date. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for colorectal cancer in relation to use of any antidepressant, SSRIs only or TCAs only, among 649 cases and 656 controls. Use of any antidepressant was associated with a reduced risk of colorectal cancer (OR = 0.7, 95% CI = 0.5–0.9). Associations were similar for persons who used SSRIs exclusively (OR = 0.7, 95% CI = 0.4–1.1) and TCAs exclusively (OR = 0.7, 95% CI = 0.5–1.2); however, this reduction in risk appeared limited to persons without a prior cancer at another site. Our data support findings from previous epidemiologic and animal studies that suggest antidepressants may reduce the risk of colorectal cancer. Future studies with larger sample sizes should further examine individual drugs as well as dose, duration and recency of use.     

Diet and risk of adult glioma in eastern Nebraska,United States

Objective: To investigate potential associations between diet and adult glioma. Methods: We conducted a population-based case–control study of adult glioma in eastern Nebraska. Nutrient and food group intakes were estimated for 236 glioma cases and 449 controls using information obtained from a food-frequency questionnaire. Results: After adjusting for potential confounders, inverse associations with risk of adult glioma were observed for intakes of dark yellow vegetables (highest quartile versus lowest: OR = 0.6, p _trend = 0.03) and beans (OR = 0.4, p _trend = 0.0003), but no associations were seen for dietary sources of preformed nitrosamines or high-nitrate vegetables. Our nutrient analysis revealed significant inverse associations between risk of adult glioma and dietary intake of pro-vitamin A carotenoids (highest quartile versus lowest: OR = 0.5, p _trend = 0.005), -carotene (OR = 0.5, p _trend = 0.01), -carotene (OR = 0.5, p _trend = 0.01), dietary fiber (OR = 0.6, p _trend = 0.048) and fiber from beans (OR = 0.5, p _trend = 0.0002). We observed no significant associations with risk of adult glioma for intakes of other nutrients or compounds including nitrate, nitrite, vitamin C, vitamin E, saturated fat, cholesterol, dietary fiber from grain products, or fiber from fruit and vegetables. Conclusion: Our study does not support the N-nitroso compound hypothesis, but suggests potential roles for carotenoids and possibly other phytochemicals in reducing risk of adult glioma.     

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.     

Non-additive and epistatic effects of HLA polymorphisms contributing to risk of adult glioma

Fatigue is the most prevalent and disabling symptom in cancer patients. Yet, scientific literature on this topic is scarce and reports disparate results. This study systematically reviews how fatigue is assessed in patients with low-grade glioma and evaluates its prevalence in LGG patients. A systematic literature search was performed in PubMed, Embase and PsychINFO for articles reporting on fatigue in patients with LGG. Two reviewers independently extracted data from selected articles. Inclusion criteria were: (1) patients with suspected or confirmed LGG; (2) fatigue was assessed as primary or secondary outcome measure; (3) age≥?18 years; (4) full-length article written in English or Dutch. In total, 19 articles were selected, including 971 patients. Seven self-assessment instruments were identified. Prevalence rates ranged from 39 to 77%. Fatigue was found to be a common side effect of treatment. The prevalence rates ranged from 20 to 76% when fatigue was reported as a mild or moderate side effect and fatigue was prevalent in 4% when reported as a severe side effect. Fatigue is a common problem in LGG patients that warrants more therapeutic and scientific attention. Gaining deeper insight in the underlying mechanisms of fatigue is essential in targeting therapy to individual patients.     

Mobile phone use and risk of glioma in 5 North European countries

Public concern has been expressed about the possible adverse health effects of mobile telephones, mainly related to intracranial tumors. We conducted a population-based case-control study to investigate the relationship between mobile phone use and risk of glioma among 1,522 glioma patients and 3,301 controls. We found no evidence of increased risk of glioma related to regular mobile phone use (odds ratio, OR = 0.78, 95% confidence interval, CI: 0.68, 0.91). No significant association was found across categories with duration of use, years since first use, cumulative number of calls or cumulative hours of use. When the linear trend was examined, the OR for cumulative hours of mobile phone use was 1.006 (1.002, 1.010) per 100 hr, but no such relationship was found for the years of use or the number of calls. We found no increased risks when analogue and digital phones were analyzed separately. For more than 10 years of mobile phone use reported on the side of the head where the tumor was located, an increased OR of borderline statistical significance (OR = 1.39, 95% CI 1.01, 1.92, p trend 0.04) was found, whereas similar use on the opposite side of the head resulted in an OR of 0.98 (95% CI 0.71, 1.37). Although our results overall do not indicate an increased risk of glioma in relation to mobile phone use, the possible risk in the most heavily exposed part of the brain with long-term use needs to be explored further before firm conclusions can be drawn.     

Epilepsy,anti‐epileptic medication use and risk of cancer

Whether the powerful medications used to treat epilepsy increase the risk of cancer has been debated for decades, but until now no study could disentangle the contributions of anti‐epileptic medications and epilepsy itself to cancer risk. Using a cohort comprising all Danish residents ≥16 years old at some point during the period 1996–2010 (>56 million person‐years of follow‐up) and information from national health registers, we examined associations between anti‐epileptic medication use and cancer rates in persons with and without epilepsy, and between epilepsy and cancer rates in treated and untreated individuals. Associations were expressed as incidence rate ratios (IRRs) estimated using Poisson regression. Among persons without epilepsy, use of anti‐epileptic medication increased the rates of most cancers little or not at all, although we observed moderately increased rates of liver, mouth and throat, and respiratory tract cancers (IRRs 1.40–1.59). In contrast, we observed strong associations between epilepsy and the rates of central nervous system and mouth and throat cancers (IRRs 2.00–3.91), and a modest association between epilepsy and the rate of respiratory tract cancers (IRRs 1.30–1.35), independent of anti‐epileptic medication use. Our finding of only modest increases in cancer risk directly attributable to anti‐epileptic medication use suggests that these medications may not be as strongly carcinogenic as has been feared, and that it is not primarily anti‐epileptic medications that are responsible for the increased cancer risk among epileptics but another aspect of epilepsy diagnosis or treatment or an etiologic factor common to the two conditions.     

Statin medication use and the risk of biochemical recurrence after radical prostatectomy

BACKGROUND:

Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate‐specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP).

METHODS:

The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features.

RESULTS:

In total, 236 (18%) men were taking statins at RP. Median follow‐up was 24 months for statin users and 38 for nonusers. Statin users were older (P < .001) and underwent RP more recently (P < .001). Statin users were diagnosed at lower clinical stages (P = .009) and with lower PSA levels (P = .04). However, statin users tended to have higher biopsy Gleason scores (P = .002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio “HR”, 0.70; 95% confidence interval “CI”, 0.50‐0.97; P = .03), which was dose dependent (relative to no statin use; dose equivalent<simvastatin 20 mg: HR, 1.08; 95% CI, 0.66‐1.73; P = .78; dose equivalent = simvastatin 20 mg: HR, 0.57; 95% CI, 0.32‐1.00; P = .05; dose equivalent>simvastatin 20 mg: HR, 0.50; 95% CI, 0.27‐0.93; P = .03).

CONCLUSIONS:

In this cohort of men undergoing RP, statin use was associated with a dose‐dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP. Cancer 2010. © 2010 American Cancer Society.     

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82×10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48×10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83×10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.     

Reproductive factors and exogenous hormone use and risk of adult glioma in women in the NIH‐AARP Diet and Health Study

Experimental evidence suggests that estrogen and other steroid hormones may protect against glioma. Although epidemiologic studies provide only weak support for a role of exogenous or endogenous hormones in gliogenesis, few cohort studies have addressed this question. The authors, therefore, examined the association between menstrual and reproductive factors, exogenous hormone use, and glioma risk among 225,355 women aged 50–71 years who completed the baseline questionnaire in the NIH‐AARP Diet and Health Study. During 7.5 years of follow‐up, 174 cases of incident, primary glioma were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for exposures, taking potential confounders into account. Older age at menarche was positively associated with risk: HR 1.67 (95% CI: 1.03, 2.69). Other reproductive factors, including age at first live birth, parity, age at menopause, type of menopause (natural vs. medical) and exogenous hormone use showed no association with glioma risk. The results were similar when the analysis was restricted to cases with glioblastoma (N = 130). The present study provides only limited support for the hypothesis that menstrual/reproductive factors or exogenous hormone use play a role in gliogenesis.     

Reproductive factors and hormone use and risk of adult gliomas

Previous research suggests there may be a hormonal influence on glioma risk as evidenced by lower rates in females, change in incidence rates around ages at menarche and menopause, and presence of hormone receptors in glial tumors. Using the large San Francisco Bay Area Adult Glioma Study, we investigated whether reported reproductive factors and hormone use were associated with gliomas overall or with histologic subtypes among female cases (n = 619) and controls (n = 650). We found that reproductive factors were generally not associated with gliomas. Weak to moderately elevated odds ratios were observed for self-reported later age at menarche (14+ vs. 12–13 years old: adjusted odds ratio (AOR) = 1.39, 95% confidence interval (CI): 1.02–1.89), particularly for non-glioblastoma histologies (AOR = 1.64, 95% CI: 1.11–2.43). Inverse associations were observed for ever self-reported use of exogenous hormones (oral contraceptive use: AOR = 0.72, 95% CI: 0.53–0.99; postmenopausal hormone use: AOR = 0.56, CI: 0.37–0.84). However, cumulative hormone exposure defined multiple ways demonstrated no clear pattern of association. The results of this study suggest that any protective effect of hormones on gliomas may be limited to exogenous hormones, but a more detailed history of exogenous hormone use is needed to confirm findings.