Pharmaceuticals Other Than Hormones

Habel, Laurel A.; Friedman, Gary D.

doi:10.1093/acprof:oso/9780195149616.003.0025

Cited by 11 publications

(22 citation statements)

References 226 publications

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“…The association of calcium channel blockers such as diltiazem has been subjected to considerable epidemiological study including control for confounders, mostly with negative results (30). A recent meta-analysis of randomized controlled trials found no increased risk for calcium channel blockers (31).…”

Section: Discussionmentioning

confidence: 99%

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Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

Friedman

Udaltsova

Chan

et al. 2009

Cancer Causes Control

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Objective-We screened commonly used prescription drugs for possible carcinogenic effects.Methods-In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment.Results-There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer.Conclusions-These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine.Many adults and children take medications regularly, yet relatively few drugs have undergone significant long-term post-marketing surveillance for adverse effects, including elevated cancer risk. In September 2006 the Institute of Medicine's Committee on the Assessment of the US Drug Safety System recommended substantial increases in safety studies of marketed drugs (1). [6][7][8][9][10][11][12]. The results of our previous screening studies were cited as providing data on 18 of the drugs evaluated and as the only source of data on humans for 9 of these.With region-wide implementation achieved by August, 1994, the Kaiser Permanente Medical Care Program (KPMCP) in northern California employs a Pharmacy Information Management System (PIMS) that records all prescriptions dispensed to its subscribers, now numbering over 3 million. Drawing upon this newer resource and a region-wide cancer registry we have screened for possible carcinogenic effects 105 commonly used drugs that were not studied in the previous smaller database, mostly because they were introduced after 1973. We here present associations that are sufficiently strong and convincing, by both a few screening criteria and further evaluation, that more detailed study is suggested to help differentiate those that are causal from those that are due to unrecognized confounding or simply to chance, given the large number of possible associations generated. Study population and methods SettingThe KPMCP is an integrated prepaid health care delivery system that provides comprehensive inpatient and outpatient care, including pharmacy services, to over 3 million current members, who comprise ab...

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Section: Discussionmentioning

confidence: 99%

“…Similarly, attention in humans has been focused primarily on breast cancer. The evidence has been mixed (30, 33, 34, 44). No human data concerning testicular cancer were found.…”

Section: Discussionmentioning

confidence: 99%

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

Friedman

Udaltsova

Chan

et al. 2009

Cancer Causes Control

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“…The data concerning cyclophosphamide were too scanty, with wide confidence limits, for any conclusions to be drawn about its apparent small risk elevation. Indomethacin is in the class of nonsteroidal anti-inflammatory drugs (NSAIDs), have usually been associated with reduced risk of breast cancer in other epidemiological studies (16). …”

Section: Discussionmentioning

confidence: 99%

“…Regarding other animal mammary carcinogens (1), phenacetin was included in analgesic combinations recorded only in the earlier cohort as it has been removed from the market. We did not study it because of large unknown over-the-counter use, and because urinary tract cancers have been clearly associated only with high-cumulative-dose abuse (16), which we believe is rare in this population. Because female hormones have been studied intensively as possible breast cancer risk factors with control for several possible confounders (17) we did not include Norlestrin (norethindrone and ethinyl estradiol) (1) in this study.…”

Section: Methodsmentioning

confidence: 99%

Pharmaceuticals that cause mammary gland tumors in animals: findings in women

Friedman

Jiang

Udaltsova

et al. 2008

Breast Cancer Res Treat

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Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: 1) earlier cohort: 78,118 female members who received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and 2) later cohort: 3,289,408 female members who received prescriptions in 1994-2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30, 2006. Ten randomly selected concurrent control women were age-matched to almost every case. Relative risks were estimated by conditional logistic regression. Case ascertainment was lagged by two years, or unlagged and subdivided by number of prescriptions received. Some analyses were controlled for hormone use and sensitivity analyses were conducted to estimate the effects of uncontrolled confounding. In the later cohort furosemide, and metronidazole showed statistically significant but very small increases in relative risk (ranging from 1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed significant increases in the later cohort: relative risk for three or more prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive confounding and non-significant increases were noted in the earlier cohort. Our findings are limited by their inconsistency across the two cohorts and our inability to directly control for most established breast cancer risk factors. Although inconclusive, our findings suggest a need for more research on furosemide and griseofulvin. Recently, Rudel et al. provided a comprehensive review of chemicals found to cause mammary tumors in animals (1). The review identified 216 chemicals associated with an increase in mammary tumors in at least one study. Of these, 47 were pharmaceuticals.As part of a project to screen pharmaceutical drugs for possible carcinogenicity (2,3) we have examined data in a large group of women to determine whether use of some pharmaceuticals among these substances is associated with an increased risk of developing breast cancer. We here report findings for cyclophosphamide, furosemide, griseofulvin, indomethacin, isoniazid, metronidazole, nitrofurantoin and reserpine. These were the only drugs listed in the review (1) on which we had sufficient data, and on which study in our setting was appropriate as explained below.Cyclophosphamide is used for treatment of some cancers and auto-immune disorders and to prevent rejection of transplanted organs. Furosemide is a diuretic used for treatment of hypertension and fluid retention due to congestive heart failure or liver or kidney disease. Griseofulvin is used to treat fungal infections of the skin, hair and nails. Indomethacin is an anti-inflammatory drug used to treat rheumatoid disorders...

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“…AC is a metabolite of the drug phenacetin, the use of which is associated with an increased risk of tumors of the bladder and renal pelvis [1]. In experimental systems AC administration in supra-therapeutic doses leads to inhibition of DNA repair, and some of the metabolites of AC have been found to be mutagenic [2, 3].…”

Section: Introductionmentioning

confidence: 99%

Use of acetaminophen in relation to the occurrence of cancer: a review of epidemiologic studies

Weiss

2016

Cancer Causes Control

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Acetaminophen has several pharmacologic properties that suggest it could be carcinogenic in human beings. A number of epidemiologic studies have been conducted to examine whether use of acetaminophen actually predisposes to the occurrence of one or more forms of cancer. There are inherent limitations to many of these studies, including the inaccurate identification of users and nonusers of acetaminophen, relatively short follow-up for cancer incidence, and the potential for confounding by indication. The present manuscript reviews the results of epidemiologic studies of acetaminophen use in relation to cancer incidence published through the end of 2015. The limitations of the underlying studies notwithstanding, some interim conclusions can be reached. For all but several forms of cancer, there is no suggestion that persons who have taken acetaminophen are at altered risk, even persons who have consumed a large quantity of the drug or those who have taken it for an extended duration. While in some studies the incidence of renal cell carcinoma has been observed to be increased among acetaminophen users, several other studies have failed to observe any such association; the reason for the discrepant findings is unclear. Some of the small number of studies that have presented data on the incidence of lymphoma, leukemia, and plasma cell disorders have found the risk to be modestly higher in users than nonusers of acetaminophen, but the results of other studies of these malignancies will be needed to gauge the possible role of publication bias as the basis for the positive results.

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Pharmaceuticals Other Than Hormones

Cited by 11 publications

References 226 publications

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

Pharmaceuticals that cause mammary gland tumors in animals: findings in women

Use of acetaminophen in relation to the occurrence of cancer: a review of epidemiologic studies

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