Use of non‐steroidal anti‐inflammatory drugs and risk of non‐Hodgkin lymphoma: a systematic review and meta‐analysis

Epidemiological study findings regarding the association between use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and risk of non‐Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta‐analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I‐squared (I²) tests; and sources of heterogeneity were explored using subgroup and meta‐regression analyses. A total of 17 studies (12 case‐control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90–1.22] or NHL subtypes including B‐cell lymphoma, T‐cell lymphoma, follicular lymphoma, diffuse large B‐cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54–0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89–1.17). Use of non‐aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01–1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed. Copyright © 2014 John Wiley & Sons, Ltd.     

Aspirin,nonsteroidal anti‐inflammatory drugs,paracetamol and risk of endometrial cancer: A case–control study,systematic review and meta‐analysis

Aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population‐based case–control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta‐analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta‐analysis risk estimates were pooled using a random‐effects model. In our case–control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63‐0.97]. There was a significant inverse dose–response (p‐trend <0.001) such that women who reported using ≥2 aspirin/week had almost half the risk OR = 0.54 (0.38–0.78). No significant associations were observed between use of half‐aspirin/day, non‐aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta‐analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79–0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m²) was 0.72 (0.58–0.90) but there was no association for non‐obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women.     

Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma

Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.     

Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow-up study

Nonsteroidal antiinflammatory drugs (NSAIDs) use, particularly aspirin, may lower the risk of several cancers, including bladder. NSAIDs may reduce development of bladder tumors by decreasing inflammation, inhibiting cycloxygenase-2, inhibiting proliferation and inducing apoptosis of cancer cells. However, acetaminophen, a major metabolite of phenacetin, may be positively associated with bladder cancer risk. Results from case-control studies on NSAIDs and acetaminophen use and bladder cancer risk are inconsistent. We investigated the association between NSAID and acetaminophen use and bladder cancer risk in a large cohort of US males. Among 49,448 men in the Health Professionals Follow-Up Study, 607 bladder cancer cases were confirmed during 18 years of follow-up. Relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models. Multivariate RR were adjusted for age, current smoking status, pack years, geographic region and fluid intake. No significant associations were observed for regular aspirin (> or =2 tablets per week), (RR = 0.99, 95% CI 0.83-1.18), ibuprofen (RR = 1.11, 95% CI 0.81-1.54), acetaminophen (RR = 0.96, 95% CI 0.67-1.39) or total NSAID use (not including acetaminophen; RR = 1.01, 95% CI 0.85-1.20) and bladder cancer risk compared with nonuse. Consistent use (over 6 years) of aspirin, ibuprofen, acetaminophen and total NSAIDs, compared to nonuse, was not associated with bladder cancer risk. No association was observed between aspirin frequency and dose and bladder cancer risk. We observed no effect-modification by smoking, age or fluid intake. Our results suggest that regular NSAID or acetaminophen use has no substantial impact on bladder cancer risk among men.     

Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer

To date, no prospective studies have explored the relationship between the use of aspirin, other nonsteroidal anti-inflammatory medications (NSAID), and acetaminophen and endometrial adenocarcinoma. Of the 82,971 women enrolled in a prospective cohort study, 747 developed medical record-confirmed invasive endometrial cancer over a 24-year period. Use of aspirin was ascertained from 1980 to 2004, and for other NSAIDs and acetaminophen, from 1990 to 2004. Cox regression models calculated multivariate relative risks (MV RR), controlling for body mass index (BMI), postmenopausal hormone (PMH) use, and other endometrial cancer risk factors. Currency, duration, and quantity of aspirin were not associated with endometrial cancer risk overall [current use: MV RR, 1.03; 95% confidence interval (CI) 0.83-1.27; >10 years of use: MV RR, 1.01; 95% CI, 0.78-1.30; and cumulative average >7 tablets per week: (MV RR, 1.10; 95% CI, 0.84-1.44)]. However, stratified analyses showed that a lower risk of endometrial cancer among obese (BMI, >or=30 kg/m(2)) women was seen with current aspirin use (MV RR, 0.66; 95% CI, 0.46-0.95). The greatest risk reduction for current aspirin users was seen in postmenopausal obese women who had never used PMH (MV RR, 0.43; 95% CI, 0.26-0.73). The use of other NSAIDs or acetaminophen was not associated with endometrial cancer. Our data suggest that use of aspirin or other NSAIDs does not play an important role in endometrial cancer risk overall. However, risk was significantly lower for current aspirin users who were obese or who were postmenopausal and had never used PMHs; these subgroup findings require further confirmation.     

Markers of inflammation and risk of ovarian cancer in Los Angeles County

Factors that increase inflammation have been suggested to influence the development of ovarian cancer, but these factors have not been well studied. To further investigate this question, we studied the role of talc use, history of endometrioisis and use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and risk of ovarian cancer in a population‐based case‐control study in Los Angeles County involving 609 women with newly diagnosed epithelial ovarian cancer and 688 population‐based control women. Risk of ovarian cancer increased significantly with increasing frequency and duration of talc use; compared to never users risk was highest among long‐duration (20+ years), frequent (at least daily) talc users (adjusted relative risk (RR) = 2.08, 95% confidence interval (CI) = 1.34–3.23). A history of physician‐diagnosed endometriosis was statistically significantly associated with risk (RR = 1.66, 95% CI = 1.01–2.75). Women who were talc users and had a history of endometriosis showed a 3‐fold increased risk (RR = 3.12, 95% CI = 1.36–7.22). Contrary to the hypothesis that risk of ovarian cancer may be reduced by use of NSAIDs; risk increased with increasing frequency (per 7 times/week, RR = 1.27, 95% CI = 1.14–1.43) and years of NSAID use (per 5 years of use, RR = 1.25, 95% CI = 1.10–1.42); this was consistent across types of NSAIDs. We conclude that risk of ovarian cancer is significantly associated with talc use and with a history of endometriosis, as has been found in previous studies. The NSAID finding was unexpected and suggests that factors associated with inflammation are associated with ovarian cancer risk. This result needs confirmation with careful attention to the reasons for NSAID use. © 2008 Wiley‐Liss, Inc.     

Aspirin,other NSAIDs,and ovarian cancer risk (United States)

Objective: We sought to evaluate the association between ovarian cancer risk and use of aspirin and nonsteroidal anti-inflammatories. Methods: We prospectively assessed use of aspirin, nonsteroidal anti-inflammatories (NSAIDs), and acetaminophen use in relation to ovarian cancer risk among 76,821 participants in the Nurses' Health Study who had no history of cancer other than non-melanoma skin cancer. Women reported known and suspected ovarian cancer risk factors in biennial mailed questionnaires from 1976 to 1996, along with new diagnoses of ovarian cancer. Aspirin use was assessed in 1980, 1982, 1984, and 1988–1994. We assessed NSAID use in 1980, and both NSAID and acetaminophen use in 1990, 1992, and 1994. During 16 years of follow-up and 1,222,412 person-years, 333 cases of invasive epithelial ovarian cancer were confirmed. We used pooled logistic regression to control for age, body mass index, oral contraceptive use, smoking history, parity, postmenopausal hormone use, tubal ligation, and other potential ovarian cancer risk factors. Results: Aspirin use was not associated with ovarian cancer risk overall (RR for users compared with nonusers, 1.00, 95% confidence interval (CI 0.80–1.25). We found no association between aspirin dose (in number of weekly tablets) and ovarian cancer risk (RR for those taking 15 or more tablets weekly compared with nonusers, 0.98, 95% CI 0.63–1.52). Similarly, duration of aspirin use was not associated with risk (RR for aspirin use of 20 or more years, 0.99, 95% CI 0.69–1.43). In separate models assessing the relation between NSAID use and ovarian cancer risk we found a 40% reduction in risk among NSAID users versus nonusers (RR 0.60, 95% CI 0.38–0.95). However, when we examined this relationship in terms of days of NSAID use per month, we did not observe a dose–response with increasing NSAID use. Conclusions: We observed no association between aspirin use, dose, or duration and epithelial ovarian cancer risk. Although we found a modest reduction in risk associated with NSAID use, there was no dose–effect.     

Associations of aspirin,nonsteroidal anti‐inflammatory drug and paracetamol use with PSA‐detected prostate cancer: Findings from a large,population‐based,case–control study (the ProtecT study)

Evidence from laboratory studies suggests that chronic inflammation plays an important role in prostate cancer aetiology. This has resulted in speculation that nonsteroidal anti‐inflammatory drugs may protect against prostate cancer development. We analysed data from a cross‐sectional case–control study (n_cases= 1,016; n_controls= 5,043), nested within a UK‐wide population‐based study that used prostate specific antigen (PSA) testing for identification of asymptomatic prostate cancers, to investigate the relationship of aspirin, nonsteroidal anti‐inflammatory drug (NSAID) and paracetamol use with prostate cancer. In conditional logistic regression models accounting for stratum matching on age (5‐year age bands) and recruitment centre, use of non‐aspirin NSAIDs [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.04–1.67] or all NSAIDs (OR = 1.25; 95% CI = 1.07–1.47) were positively associated with prostate cancer. There were weaker, not conventionally statistically significant, positive associations of aspirin (OR = 1.13; 95% CI = 0.94–1.36) and paracetamol (OR = 1.20; 95% CI = 0.90–1.60) with prostate cancer. Mutual adjustment for aspirin, non‐aspirin NSAIDs or paracetamol made little difference to these results. There was no evidence of confounding by age, family history of prostate cancer, body mass index or self‐reported diabetes. Aspirin, NSAID and paracetamol use were associated with reduced serum PSA concentrations amongst controls. Our findings do not support the hypothesis that NSAIDs reduce the risk of PSA‐detected prostate cancer. Our conclusions are unlikely to be influenced by PSA detection bias because the inverse associations of aspirin, NSAID and paracetamol use with serum PSA would have attenuated (not generated) the observed positive associations.     

Use of aspirin,other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium

BackgroundRegular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited.Patients and methodsWe pooled individual-level data from seven cohort and five case–control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect.ResultsAt least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76–0.98] and 0.86 [95% CI 0.76–0.97], respectively, for aspirin; 0.87 [95% CI 0.76–1.00] and 0.84 [0.74–0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m², P_{heterogeneity} = 0.04 for aspirin, P_{heterogeneity} = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2–6 times/week (OR = 0.81, 95% CI 0.68–0.96) than for daily use (0.91, 0.80–1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen.ConclusionOur pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.     

Aspirin and nonsteroidal anti-inflammatory drug use and risk of pancreatic cancer: a meta-analysis.

BACKGROUND: The association between use of nonsteroidal anti-inflammatory drugs (NSAID), including aspirin, and risk of pancreatic cancer is controversial. We did a meta-analysis to summarize available evidence from epidemiologic studies investigating the relation between use of aspirin or other NSAIDs and the risk of pancreatic cancer. METHODS: We identified potential studies by searching the MEDLINE database (from 1966 to October 2006) and by reviewing the reference lists of pertinent publications. Studies were eligible for inclusion if they met the following criteria: (a) had a case-control or prospective design, (b) examined exposure to aspirin or NSAIDs, (c) the outcome was pancreatic cancer incidence or mortality, and (d) they provided a relative risk (RR) estimate with corresponding confidence interval or sufficient information to permit their calculation. Study-specific RR estimates were pooled using a random effects model. RESULTS: A total of 11 studies (3 case-control studies, 7 cohort studies, and 1 randomized trial), involving 6,386 pancreatic cancer cases, was included in the meta-analysis. The summary RR estimate did not indicate any association between aspirin/NSAID use and risk of pancreatic cancer [any/regular use versus nonregular/never use: RR, 1.01; 95% confidence interval (95% CI), 0.91-1.11; P(heterogeneity) = 0.09]. Neither use of aspirin, nonaspirin NSAIDs, nor overall NSAIDs were associated with pancreatic cancer risk. There was also no overall association with frequent (six or more tablets/times per week versus none: RR, 0.86; 95% CI, 0.61-1.23) or long-term (>or=20 years) use of aspirin (RR, 1.21; 95% CI, 0.74-1.96). CONCLUSIONS: Current epidemiologic evidence does not indicate that use of aspirin or NSAIDs is associated with the risk of pancreatic cancer.     

Non‐steroidal anti‐inflammatory drugs and cancer risk in women: Results from the Women's Health Initiative

The use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced risks of cancers at several sites in some studies; however, we recently reported no association between their use and total cancer risk in women in a prospective study. Here we examine the association between NSAIDs and total and site‐specific cancer incidence in the large, prospective Women's Health Initiative (WHI). Women (129,013) were recruited to participate in the WHI at 40 US clinical centers from 1993 to 1998 and followed prospectively. After 9.7 years of follow‐up, 12,998 incident, first primary, invasive cancers were diagnosed. NSAID use was systematically collected at study visits. We used Cox proportional hazards regression models to estimate multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs use and total and site‐specific cancer risk. Relative to non‐use, consistent use (i.e., use at baseline and year 3 of follow‐up) of any NSAID was not associated with total cancer risk (HR 1.00, 95% CI: 0.94–1.06). Results for individual NSAIDs were similar to the aggregate measure. In site‐specific analyses, NSAIDs were associated with reduced risks of colorectal cancer, ovarian cancer, and melanoma. Our study confirms a chemopreventive benefit for colorectal cancer in women and gives preliminary evidence for a reduction of the risk of some rarer cancers. NSAIDs' benefit on cancer risk was therefore limited to specific sites and not evident when total cancer risk was examined. This information may be of importance when NSAIDs are considered as chemopreventive agents.     

Association between physical activity and all cancer mortality: Dose–response meta‐analysis of cohort studies

The relationship between physical activity (PA) before cancer diagnosis and all cancer mortality among the general population is not well defined because of inconsistent results from published studies. Thus, the lack of a meta‐analysis that addresses that issue prompted the current report. We conducted a literature search of PubMed and Web of Science to identify all relevant epidemiological studies published before February 28, 2015. We performed categorical and dose–response meta‐analyses to evaluate and quantify the association between pre‐diagnosis PA and all cancer mortality. A total of 32 prospective cohort studies involving 59,362 cancer deaths were included in this meta‐analysis. The pooled relative risks (RRs) of all cancer mortality were 0.80 [95% confidence interval (CI) = 0.76–0.85)] for highest versus lowest PA group and 0.85 (95% CI = 0.82–0.88) for PA versus non/occasional PA group. Dose–response analysis showed that the increment in pre‐diagnosis PA level was associated with a decreased risk of cancer death continuously. Moreover, an increment of 10 MET‐h/week was related to a 7% lower risk for all cancer mortality (RR = 0.93, 95% CI = 0.91–0.95). In conclusion, the present meta‐analysis provides evidence of an inverse association between pre‐diagnosis PA and all cancer mortality among the general population. High‐quality epidemiological studies that employ standardized PA assessments and unified definitions of PA levels should be developed in future.     

Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow‐up study

Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non‐vitamin, non‐mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow‐up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred. Cox proportional hazards regression was used to estimate relative risks (RRs) within each cohort, and results were pooled using a random effects meta‐analysis. Associations were comparable across cohorts, with a RR of 0.79 (95% CI: 0.63–1.00) observed for any use of glucosamine and a RR of 0.77 (95% CI: 0.59–1.01) observed for any use of chondroitin. Use of glucosamine in the absence of chondroitin was not associated with risk of CRC, whereas use of glucosamine + chondroitin was significantly associated with risk (RR: 0.77; 95% CI: 0.58–0.999). The association between use of glucosamine + chondroitin and risk of CRC did not change markedly when accounting for change in exposure status over follow‐up (RR: 0.75; 95% CI: 0.58–0.96), nor did the association significantly vary by sex, aspirin use, body mass index, or physical activity. The association was comparable for cancers of the colon and rectum. Results support a protective association between use of glucosamine and chondroitin and risk of CRC. Further study is needed to better understand the chemopreventive potential of these supplements.     

Use of nonsteroidal anti‐inflammatory drugs and prostate cancer risk: A meta‐analysis

The association between use of aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDs) and the risk of prostate cancer remains controversial despite many observational epidemiological studies. We conducted a systematic meta‐analysis of these studies to examine both the strength and the consistency of the association, and to explore sources of variability between studies. We searched 12 computerized literature databases for reports published before June 2008 and included any epidemiologic studies where the outcome was prostate cancer incidence or mortality, and the exposure was use of NSAIDs. Studies that met the inclusion criteria comprised 10 case–control and 14 cohort studies with a total of 24,230 prostate cancer cases. Studies that assessed the effect of aspirin use on total prostate cancer had a pooled odds ratio (POR) of 0.83 (95%CI: 0.77–0.89), whereas those that assessed the effect of aspirin on advanced prostate cancer had a POR of 0.81 (0.72–0.92). Studies that examined the effects of non‐aspirin NSAIDs or all NSAIDs were less consistent but still suggestive of reduced risks. However, most reviewed studies were limited by exposure and disease misclassification, by inadequate information on dose and duration of use and by the possibility of screening and other biases. In conclusion, the epidemiologic evidence for a protective effect of aspirin and other NSAID use against prostate cancer is suggestive but not conclusive. There is a need for well‐designed observational studies with adequate exposure measurements, accurate case definition, attention to latency effects, and careful adjustment for screening and other biases.     

Obesity and incidence of lung cancer: A meta‐analysis

To date, the relationship between obesity and the incidence of lung cancer remains unclear and inconclusive. Thus, we conducted a meta‐analysis of published studies to provide a quantitative evaluation of this association. Relevant studies were identified through PubMed and EMBASE databases from 1966 to December 2011, as well as through the reference lists of retrieved articles. A total of 31 articles were included in this meta‐analysis. Overall, excess body weight (body mass index, BMI ≥ 25 kg/m²) was inversely associated with lung cancer incidence (relative risk, RR = 0.79; 95% confidence interval, CI: 0.73–0.85) compared with normal weight (BMI = 18.5‐24.9 kg/m²). The association did not change with stratification by sex, study population, study design, and BMI measurement method. However, when stratified by smoking status, the inverse association between excess body weight and lung cancer incidence in current (RR = 0.63, 95% CI: 0.57–0.70) and former (RR = 0.73, 95% CI: 0.58–0.91) smokers was strengthened. In non‐smokers, the association was also statistically significant (RR = 0.83, 95% CI: 0.70–0.98), although the link was weakened to some extent. The stratified analyses also showed that excess body weight was inversely associated with squamous cell carcinoma (RR = 0.68, 95% CI: 0.58–0.80) and adenocarcinoma (RR = 0.79, 95% CI: 0.65–0.96). No statistically significant link was found between excess body weight and small cell carcinoma (RR = 0.99, 95% CI: 0.66–1.48). The results of this meta‐analysis indicate that overweight and obesity are protective factors against lung cancer, especially in current and former smokers.     

Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis

The association between non-steroidal anti-inflammatory drugs (NSAIDs) use and breast cancer has remained controversial. Therefore, an overall quantitative estimate of the association needs to be studied. A systematic review and meta-analysis was executed to explore the pooled estimate for relative risk (RR) and 95% confidence interval (CI) using random or fixed effects models based on heterogeneity analysis. Overall 26 studies with 528,705 participants were included. The RR of NSAIDs use and the incidence of breast cancer was 0.94 (95% CI: 0.88–1.00) with random effects model. A slight reduction of breast cancer by taking aspirin and ibuprofen was both observed with pooled RR of 0.91 (95% CI: 0.83–0.98) and 0.81 (95% CI: 0.67–0.97), respectively. Our results indicate that NSAIDs use is associated with a slight decrease for the development of breast cancer with a marginally statistical significant difference. The associations are slightly more obvious in aspirin and ibuprofen use.     

Age at menarche and risk of ovarian cancer: A meta‐analysis of epidemiological studies

Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta‐analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T‐T.G. and Q‐J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random‐effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case–control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case–control studies were 0.89 (95% CI = 0.76–1.03) and 0.84 (95% CI = 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta‐analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.     

Medication use and risk of ovarian carcinoma: a prospective study

Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study.     

Adherence to Mediterranean diet and risk of cancer: A systematic review and meta‐analysis of observational studies

The aim of this research study was to meta‐analyze the effects of adherence to Mediterranean diet (MD) on overall cancer risk, and different cancer types. Literature search was performed using the electronic databases MEDLINE, SCOPUS and EMBASE until January 10, 2014. Inclusion criteria were cohort or case–control studies. Study specific risk ratios (RRs) were pooled using a random effect model by the Cochrane software package Review Manager 5.2. Twenty‐one cohort studies including 1,368,736 subjects and 12 case–control studies with 62,725 subjects met the objectives and were enclosed for meta‐analyses. The highest adherence to MD category resulted in a significantly risk reduction for overall cancer mortality/incidence (cohort; RR: 0.90, 95% CI 0.86–0.95, p < 0.0001; I² = 55%), colorectal (cohort/case–control; RR: 0.86, 95% CI 0.80–0.93, p < 0.0001; I² = 62%], prostate (cohort/case–control; RR: 0.96, 95% CI 0.92–0.99, p = 0.03; I² = 0%) and aerodigestive cancer (cohort/case–control; RR: 0.44, 95% CI 0.26–0.77, p = 0.003; I² = 83%). Nonsignificant changes could be observed for breast cancer, gastric cancer and pancreatic cancer. The Egger regression tests provided limited evidence of substantial publication bias. High adherence to a MD is associated with a significant reduction in the risk of overall cancer mortality (10%), colorectal cancer (14%), prostate cancer (4%) and aerodigestive cancer (56%).     

Coffee consumption and risk of colorectal cancer: A systematic review and meta‐analysis of prospective cohort studies

An inverse association between coffee consumption and the risk of colorectal cancer has been found in several case‐control studies, but such an association was not consistent in prospective cohort studies. We conducted a systematic meta‐analysis of prospective cohort studies on coffee consumption and colorectal cancer published up to June 2008. We combined relative risks (RR) for colorectal cancer comparing high vs. low categories of coffee consumption using random‐effects models. We identified 12 eligible cohort studies, which included 646,848 participants and 5,403 cases for colorectal cancer. The summarized result of the meta‐analysis comparing high‐ vs. low‐consumption categories showed no significant effect of coffee consumption on colorectal cancer risk (RR = 0.91; 95% confidence intervals [CI]: 0.81–1.02). The RR was 0.93 (95% CI: 0.71–1.22) when considering 4 studies conducted in the United States of America, 0.91 (95% CI: 0.76–1.10) for 5 studies from Europe, and 0.83 (95% CI: 0.62–1.10) for 3 Japanese studies. No significant differences by sex and cancer‐site were found, but there was a slight suggestion of an inverse association between coffee consumption and colon cancer in women (RR = 0.79; 95% CI: 0.60–1.04), especially Japanese women (RR = 0.62; 95% CI: 0.37–1.05). The suggestive inverse associations were slightly stronger in studies that controlled for smoking and alcohol, and in studies with shorter follow‐up times. Information on coffee type, its serving size, or brewing method may provide a better understanding of this reassuring result and the real role of coffee on colorectal cancer risk. © 2008 Wiley‐Liss, Inc.