Aspirin In Prevention Of Cancer Research Articles

Abstract A27: The relationship between aspirin and cancer via its inhibition of mTOR pathway

Abstract Aspirin, a nonsteroidal anti-inflammatory drug, has been used clinically as a painkiller, antipyretic or antiplatelet agent for more than 100 years. Several trials demonstrate that the nonsteroidal anti-inflammatory agent aspirin prevents NETs (neuroendocrine tumors), colorectal cancer (CRC), hepatocellular carcinoma (HCC), melanoma, glioma, bladder cancer, pancreatic cancer (PC), breast and prostate cancers and reduces cancer mortality, indicating a promising role of aspirin for cancer prevention. In literature, we can see that most of them are clinical studies. For more effective treatment we need to understand molecular mechanism. In this study, we reviewed the relationship between aspirin and mTOR pathway in types of cancer mentioned above, particularly CRC since it is better defined. The main question is: How can aspirin inhibit the cancer development by using mTOR pathway? The benefit-to-risk ratio must be defined in different cancer types as side effects. Mammalian target of rapamycin (mTOR) is highly expressed in the processes of multiple types of tumors. mTOR forms the catalytic core of 2 distinct complexes, mTORC1 and mTORC2. mTORC1 integrates growth factor and nutrient signals to influence protein synthesis, growth, autophagy, and ribosomal biogenesis. The role of mTORC2 is less well defined. Aspirin reduced the incidence and mortality of colorectal cancer by activating the adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK)/mTOR pathway and contributed to protection against the development of CRC. Aspirin inhibits mTORC1 signaling in an AMPK-independent manner. AMPK plays a major role in cellular energy hemostasis and leads to mTOR suppression. Some studies investigated the effects of aspirin on AMPK/mTOR signaling and showed that aspirin alone or the combination of aspirin and metformin activates AMPK and inhibits mTOR signaling in colorectal cancer cells. Furthermore, mutations in phosphatidylinositol 3-kinase (PI3K) signaling genes occur in 40% of CRCs and that pathway is important in regulating the cell cycle, although mTOR is a downstream effector of the PI3K/AKT pathway. In PC, NETs and CRC the PI3K/Akt/mTOR pathway is deregulated in the majority of tumors, and the activation of this pathway correlates significantly with a poor prognosis. A link between cancer and metabolism has been long suggested. Additionally, aspirin induced autophagy, a feature of mTOR inhibition. So mTOR exists in a phosphorylated form in normal conditions and suppresses autophagy. Much available evidence supports AMPK/mTOR signaling as a chemoprevention target. Some studies have suggested that aspirin is a promising agent for adjuvant therapy to increase survival. However, the mechanism of combination and its effects on patients require further prospective investigations. In conclusion, aspirin inhibits the cancer development and progression by using mTOR signaling pathway. Note: This abstract was not presented at the conference. Citation Format: Bulent Karabulut, Oyku Ay. The relationship between aspirin and cancer via its inhibition of mTOR pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A27.

Abstract 4667: Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts

Abstract Purpose: Daily low-dose aspirin is recommended for certain individuals for prevention of cardiovascular disease and colorectal cancer. However, there are known risks associated with aspirin use. Identifying subgroups of individuals most likely to benefit from aspirin for cancer prevention would help to tailor risk-benefit calculations to maximize benefits and minimize risks. We investigated whether associations between daily aspirin use and risk of several cancers vary by other cancer risk factors, including age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer. Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011), a population-based cohort study, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009), a multicenter randomized controlled trial. Daily aspirin use was self-reported at baseline and defined as use ≥5 days/week. Our main outcome measures were incident colorectal, ovarian, breast, endometrial, and aggressive prostate cancers. We used multivariable Cox proportional hazards regression to examine associations between daily aspirin use and risk of each cancer, overall and across strata of risk factors. Results: Compared with non-use and non-daily use, daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.80-0.89). Risk reductions were generally consistent across strata of other risk factors but attenuated with increasing BMI (p-interaction=0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI: 0.80-1.08) but a reduced risk among obese women (HR: 0.73, 95% CI: 0.52-0.98, p-interaction=0.12). We observed suggestive modest risk reductions for breast (HR: 0.96, 95% CI: 0.91-1.00) and aggressive prostate (HR: 0.95, 95% CI: 0.90-1.00) cancer and a null association for endometrial cancer (HR: 0.96, 95% CI: 0.86-1.07), with no strong effect modification observed. Conclusions: Daily aspirin use was associated with reduced colorectal cancer risk across strata of cancer risk factors. The magnitude of the benefit varied by BMI for colorectal cancer and was restricted to obese women for ovarian cancer. The potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use. Citation Format: Lauren M. Hurwitz, Kara A. Michels, Michael B. Cook, Ruth M. Pfeiffer, Britton Trabert. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4667.

Long-term use of low-dose aspirin for cancer prevention: A 10-year population cohort study in Hong Kong.

Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, has been found to possess protective effects against cancer development in the Western populations. Such effects among Asian populations remain uncertain. The objective of this study is to investigate the use of aspirin on prevention of different cancers among Chinese users. This population-based study utilized database from the Hong Kong Hospital Authority; adults with aspirin prescription for at least 6 months between 2000 and 2004 were included and followed up until 2013. Aspirin users were age-sex matched with non-aspirin users at a 1:2 ratio. Incidences of cancer were the primary outcome measured by relative risk (RR). A total of 204,170 aspirin users and 408,339 non-aspirin users were included, with the mean age 67.5 years, 7.7 years average duration of aspirin prescription and 80 mg as the median dose of aspirin. Cancer incidences were found in 26,929 (13.2%) aspirin users and 70,755 (17.3%) non-aspirin users. Compared with patients who had not been prescribed aspirin, aspirin usage led to significant reduction of cancers in liver (RR: 0.49), stomach (RR: 0.42), colorectum (RR: 0.71), lung (RR: 0.65), pancreas (RR: 0.54), oesophagus (RR: 0.59) and leukaemia (RR: 0.67). There was no demonstrable reduction of kidney cancer, bladder cancer, prostate cancer and multiple myeloma in association with the usage of aspirin. Risk of breast cancer was shown to marginally increase (RR: 1.14) with aspirin usage. This study demonstrated that the long-term use of low-dose aspirin is associated with the reduction in risk of various cancers but not for breast cancer. Further investigation is needed before promoting aspirin as a primary chemoprotective agent.

Advances in antitumor effects of NSAIDs.

In recent years, the reports on using nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer prevention and treatment have been on the rise. In 2017, the US Preventive Services Working Group issued primary prevention guidelines on the use of NSAIDs, especially aspirin, for cardiovascular disease and colorectal cancer, and formally established the role and status of aspirin in cancer prevention. However, the mechanism of NSAIDs on preventing cancer is still not clear. In this paper, the progress of the application of NSAIDs, especially aspirin, in the prevention and treatment of tumors in recent years is summarized, and new ideas and directions for the follow-up study are also discussed.

General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: Findings from a national survey

A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p < 0.001). In multivariable analyses, willingness to prescribe (600 mg) was higher among GPs ≥50 years (OR 1.46, 95% CI 1.03-2.07), more experienced GPs (OR 1.50, 95% CI 1.10-2.04), GPs who were aware of the cancer preventive effects of aspirin (OR 1.58, 95% CI 1.20-2.09), and those who reported seeing a Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

Aspirin for Cancer Prevention

In this issue of JAMAOncology, Cao et al1 present an analysis ofaspirinuse for cancerprevention in lightof the recentUSPreventive Services Task Force (USPSTF) draft recommendation2 regarding the use of aspirin for prevention of colorectal cancer (CRC) in individuals at risk for cardiovascular disease. The USPSTF does not recommend aspirin use for the sole purpose of CRC prevention, but rather acknowledges an additional benefit of aspirin use among a group of individuals who are already likely to benefit from aspirin for the preventionof cardiovascular events.Advancing theuseof aspirin as a truecancer chemopreventiveagentwould typically requireadditional data fromdedicated randomized clinical trials regarding theabilityofaspirin toprotectagainst cancerswith thedefinition of an effective dose, the frequency and duration of treatment, and theclinicalpopulationat risk. Inaddition, aswe haveseenwiththeUSFoodandDrugAdministration’spriorconsideration of other agents for possible CRC and polyp prevention effects, the impact of such agents in the context of establishedandeffective screeningmodalities, suchas colonoscopy with polypectomy, is also important. Cao and colleagues1 attempt to address several important issuesusing2of the largest andbest-characterizedcohorts, the Nurses’ Health Study and theHealth Professionals Follow-up Study. The strengths of these cohorts include their size; the length and completeness of follow-up; the availability of reasonable, albeit self-reported,dataonaspirinuse,dose, andduration; and their thorough ascertainment of cancer incidence. In addition, the cohorts are broadly representative of the US general population in terms of prevalence of risk factors and screening rates. The investigative team iswell versed in the issues surrounding the use of aspirin as a potential preventive agent in the general population andhas experience in performing careful observational evaluations of aspirin’s effects on cancer risk.3 Their findings are generally consistent with earlier reported preventive effects of aspirin on gastrointestinal (GI) tract cancers.4 In the combined cohort analysis, regular aspirin users experienced a statistically significant 15% reduction in the risk for all GI tract cancers, with a significant 19% reduction in the risk for CRC and a nonsignificant 15% reduction in the risk for gastroesophageal cancer. They also demonstrate that protection against GI tract cancers occurs at relatively low doses (0.5-1.5 standard tablets per week) that were used for various other reasons (eg, cardioprotection, headache, arthritis, musculoskeletal pain), with greater risk reduction seen at increasing doses and with longer duration of use and 6 years suggested as the minimum duration of use needed to realize cancerprotective benefits. The associations seen with GI tract cancers and CRC were not modified by any of the numerous lifestyle and clinical variables examined. A small but statistically significant 3% reduction in overall cancer incidence (relative risk, 0.97; 95% CI, 0.94-0.99) was also seen among regular aspirin users, although this reduction is largely driven by the lower incidence of GI tract cancers within this group. Regular aspirin use was not associated with a reduced risk for breast, advanced prostate, or lung cancers in these analyses. Despite these careful analyses, perhaps the most important andunique contributions of this study1 are the team’s assessmentof aspirin’s potential population-wide impact and its absolute benefits in the context of screening. They calculated the proportion of incident cancers that could have been prevented with regular aspirin use, or the partial populationattributable risk, and found that 8.0% of all GI tract cancers and 10.8%ofCRCs couldhavebeenpreventedwith regular aspirin use. In addition, their findings suggest that regular aspirin use could have prevented 33 CRCs per 100000 personyears (17.0% of CRCs) among those who did not have lower endoscopy, and another 18 CRCs per 100000 person-years (8.5%) could have beenprevented among thosewhodid have lower endoscopy. This finding is important because it suggests that aspirinusemaycomplementCRCscreeningandmay haveanabsolutebenefit regardlessofendoscopystatus, a critical insight that few other studies have provided thus far. As the authors note, CRC screening rates remain suboptimal in theUnited States and, according to their calculations, regular aspirin use could prevent 9800 CRCs among the nearly 30 million age-eligible individuals who remain unscreened.1 Given the rising rates of CRC in low-resource settings where screening with endoscopy is often not feasible, the findings suggest that aspirin may serve as a relatively low-cost primary prevention modality to complement the wellestablished but underused preventive benefits of CRC screening with polypectomy. Although the analysis by Cao and colleagues1 provides more context to the use of aspirin as a CRC-preventive agent, the studyprovidesnoassessmentof thepotential harmsof aspirin in these cohorts and does not assess the full range of aspirin’s benefits beyond its cancer-preventive effects. Moreover, aspirin’s long-term effects, if any, on cancer and overall mortality are not addressed, although earlier observational studies suggest inverse associationswith cancer-specific and all-cause mortality.3,5,6 To reflect accurately the often complex, real-world clinical scenarios inwhichphysicians andpatients contemplate the use of aspirin, any truly informative analysis of its usemust weigh its cumulative benefits against its cumulative risks. Few studies are capable of such an assessment, but 2 ongoing randomized clinical trials of aspirin Related article page 762 Research Original Investigation Effect of Long-term Use of Aspirin on the Risk for Cancer

Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information.

A Role for Aspirin in Cancer Prevention?

Abstract Although the organizations that issue guidelines for clinical care do not recommend taking aspirin for cancer prevention, there is mounting evidence that the drug reduces the risk of colorectal and other cancers, especially in high-risk patients. The creation of databases tracking patient outcomes, as well as a better understanding of how aspirin exerts its cancer-fighting effects, could help physicians determine the best candidates for a daily regimen of low-dose aspirin to prevent disease.

Role of Aspirin in Cancer Prevention

Since its first synthesis in 1897, several medicinal roles and mechanisms of action of aspirin have become apparent; the latest among these being its role in cancer prevention and treatment. A large body of evidence supports aspirin's effect in reducing cancer incidence and cancer mortality, but duration of use needs to be at least 5 years. The beneficial effects are particularly large for colorectal, oesophageal and gastric cancers, with apparently smaller reductions for breast, prostate and lung cancer. The major harm is gastrointestinal bleeding, but serious sequelae are minimal at ages <70 years. It is very likely that use of prophylactic aspirin in the general population aged 50-70+ years will result in net overall benefit. Outstanding issues are: whether standard dose (~300 mg/day) can lead to greater net benefits than low dose (75-100 mg/day), the optimum duration of use, and appropriate ages for use in average-risk individuals.

Abstract CN04-01: Aspirin for cancer prevention: Are we there yet?

Abstract Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. Four placebo-controlled randomized controlled trials (RCTs) among individuals with a history of colorectal neoplasia showed that aspirin reduced the risk of recurrent adenomas, the precursors of the vast majority of cancers. Nonetheless, in 2007 the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin to prevent colorectal cancer in individuals at average risk. However, since the USPSTF statement, new information has emerged, persuasively making the case for a broader role for aspirin in cancer prevention. These data include long-term follow-up of a RCT of aspirin among individuals with Lynch syndrome, a hereditary colorectal cancer syndrome and secondary analyses of RCTs of aspirin for cardiovascular prevention. The latter collection of studies also showed a lower risk of all cancer and cancer-related deaths among individuals randomized to aspirin, a finding which could substantially alter the risk-benefit calculus for regular aspirin use in the general population. In addition, there are mounting data supporting an association between aspirin use and improved outcomes among colorectal cancer survivors. In this presentation, we will review the evidence supporting a role for aspirin in the prevention and treatment of cancer, with a focus on novel strategies for risk stratification. Citation Format: Andrew T. Chan. Aspirin for cancer prevention: Are we there yet? [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN04-01.

Aspirin and diabetes: prescribing attitudes reflect clinical uncertainties

Only a few years ago low-dose daily aspirin was regarded by the popular press as a ‘wonder drug’, prolonging life at least for the over-50s by combating heart disease, strokes and certain cancers as well as reducing risk, among others, of cognitive decline, cataracts and gall stones, all of which occur more commonly with diabetes. The benefit of aspirin in secondary prevention of coronary heart disease (CHD) is deemed unequivocal. Furthermore, still within recent years, expert consensus reports, including those from the American Diabetes Association, have suggested that there was also ‘substantial evidence’ (albeit based on older trials – the US Physicians Health Study, for example, reported 39% relative risk reduction for men with diabetes) for low-dose aspirin usage in the primary prevention of CHD in people with diabetes who have additional cardiovascular system (CVS) risk factors such as hypertension, smoking, dyslipidaemia and albuminuria. Diabetes itself can be associated with significant haemobiological disturbance, including increased platelet adhesiveness and aggregation, arguably of contribution to the atherogenic process and other diabetic angiopathies. Whether platelet dysfunction is a direct consequence of hyperglycaemia or secondary to vascular disease has been debated, but in vitro studies demonstrate a powerful and sustained effect of aspirin in reversing these disturbed platelet parameters, in part by blocking synthesis of thromboxane, a potent vasoconstrictor that is increased in diabetes. When a treatment hypothesis is proposed it is more easily understood if there is an intrinsic logic to the recommendation. Thus the use of aspirin in patients with established CHD can be accepted without much difficulty but, in contrast, it does seem counter-intuitive that aspirin may not be of benefit in primary prevention. Given the changing consensus guidance, based on more recent trial evidence, systematic review and risk–benefit analysis, it is still not surprising that the clinical prescriber retains significant uncertainties concerning the considered correct, but probably more importantly the most appropriate, management in respect of aspirin usage in diabetes. In reality, as more frequently expressed these days, guidelines should not necessarily be seen as ‘a one size fits all’ strategy set against the merits of determining optimal individualised care. Raghavan and colleagues report in this issue of Practical Diabetes the results of their survey of attitudes of health care professionals to the use of aspirin in diabetes for the prevention of CHD. Although it is evident that most health care professionals would no longer routinely prescribe aspirin in this context, at least half still have uncertainties as to best practice and many support the concept of individually determined need by regarding specific CVS risk factors as a positive indication for prescribing low-dose aspirin. The authors review the latest evidence base for low-dose aspirin in primary prevention and, indeed, trial data become increasingly more difficult to interpret as further confounding factors, such as increasing use of statins, complicate the overall picture. Furthermore, uncertainties concerning the appropriate dose of aspirin and the possibility of increased aspirin resistance in diabetes add yet more confusion to the dilemma. The survey identifies interesting differences in attitudes between health care professionals and between primary and secondary care settings, specialist doctors on the whole continuing to prescribe selectively for specific situations such as microalbuminuria. Diabetes has many examples of clinical practice changing with time in the light of new research review, and sometimes ‘what goes around, comes around’. It will be interesting to learn in due course of the ASCEND trial results, which include a treatment group with low-dose aspirin. Meanwhile, the potential benefit of aspirin in cancer prevention – yet to be established but with its own developing evidence base, and of relevance to diabetes particularly associated with obesity – adds but another reason not to dismiss aspirin as part of the extensive therapeutic armamentarium that so characterises the current treatment of diabetes.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

The role of aspirin in cancer prevention

Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding. Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily). This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin. It also considers how even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.

Will an aspirin a day keep the colorectal cancer away?

A long-term follow-up study that assessed the effect of daily aspirin on colorectal cancer incidence concluded that it significantly reduced the risk of colon cancer, but not rectal cancer. Detailed analysis of the findings indicate that it is too soon to recommend daily aspirin for cancer prevention in healthy individuals.

Low-dose Aspirin in the Primary Prevention of Cancer: The Women's Health Study: A Randomized Controlled Trial

Low-dose Aspirin in the Primary Prevention of Cancer: The Women's Health Study: A Randomized Controlled Trial

Low-dose Aspirin in the Primary Prevention of Cancer: The Women's Health Study: A Randomized Controlled Trial

Low-dose Aspirin in the Primary Prevention of Cancer: The Women's Health Study: A Randomized Controlled Trial

Low-Dose Aspirin in the Primary Prevention of Cancer: The Women’s Health Study: A Randomized Controlled Trial

Low-Dose Aspirin in the Primary Prevention of Cancer: The Women’s Health Study: A Randomized Controlled Trial

Low-Dose Aspirin in the Primary Prevention of Cancer. The Women’s Health Study: A Randomized Controlled Trial

Low-Dose Aspirin in the Primary Prevention of Cancer. The Women’s Health Study: A Randomized Controlled Trial

Age-related cataract in a randomized trial of beta-carotene in women

purpose To examine the development of age-related cataract in a trial of beta-carotene supplementation in women. methods The Women's Health Study is a randomized, double-masked, placebo-controlled trial originally designed to test the balance of benefits and risks of beta-carotene (50 mg on alternate days), vitamin E, and aspirin in the primary prevention of cancer and cardiovascular disease among 39,876 female health professionals aged 45 years or older. The beta-carotene component of the trial was terminated early after a median treatment duration of 2.1 years. Main outcome measures were visually-significant cataract and cataract extraction, based on self-report confirmed by medical record review. results There were 129 cataracts in the beta-carotene group and 133 in the placebo group (relative risk [RR] = 0.95, 95% CI 0.75-1.21). For cataract extraction, there were 94 cases in the beta-carotene group and 89 cases in the placebo group (RR = 1.04, 95% CI 0.78-1.39). Subgroup analyses suggested a possible beneficial effect of beta-carotene in smokers. conclusions These randomized trial data from a large population of apparently healthy female health professionals indicate that two years of beta-carotene treatment has no large beneficial or harmful effect on the development of cataract during the treatment period.

Adult height and incidence of cancer in male physicians (United States).

Adult height has been found in some but not all studies to be associated positively with overall cancer incidence as well as several site-specific cancers. The Physicians' Health Study (PHS), a randomized trial of beta-carotene and aspirin in the primary prevention of cancer and cardiovascular disease in men, provided an opportunity to examine the association between height and total malignant neoplasms (excluding non-melanoma skin cancer), as well as site-specific cancers including prostate, colorectal, and lung cancer. The PHS is comprised of 22,071 US male physicians in the United States, a population homogeneous for adult socioeconomic status, aged 40 to 84 years in 1982. Participants were classified into five height categories at study entry. After an average follow-up of over 12 years, there were 2,566 cases of incident total malignant neoplasms, including 1,047 prostate, 341 colorectal, and 170 lung cancer cases. Height was associated positively with both total malignant neoplasms and prostate cancer. Compared with men in the shortest category (<67 inches), relative risks and 95 percent confidence intervals (CI) for total malignant neoplasms for men whose height (in inches) was 68-69, 70-71, 72, and 73+ were, respectively: 1.13 (CI = 0.99-1.28), 1.15 (CI = 1.02-1.30), 1.29 (CI = 1.12-1.49), and 1.21 (CI = 1.05-1.39), P trend 0.001, adjusted for age, randomized treatment assignments, body mass index (wt/ht2), cigarette smoking, alcohol use, and exercise frequency. For prostate cancer, the corresponding RR values were 1.23 (CI = 1.00-1.51), 1.26 (CI = 1.04-1.54), 1.59 (CI = 1.27-1.98), and 1.26 (CI = 1.00-1.59), P trend 0.005. For colorectal cancer, in some but not all height categories compared with the shortest, there were elevated RRs without a significant linear trend: RR = 1.51 (CI = 1.06-2.14), 1.14 (CI = 0.80-1.62), 1.19 (CI = 0.79-1.80), and 1.53 (CI = 1.04-2.25), P trend 0.23. In contrast, there was no evidence of an association of height with lung cancer. These data indicate a positive association between height and risk of total malignant neoplasms, as well as of prostate cancer and, possibly, colorectal cancer.