Search

Purpose: Determine the risk of subsequent cancer following squamous cell skin cancer.Methods: Using computerized surgical pathology records and membership data from a health maintenance organization, we retrospectively identified 822 individuals with primary squamous cell skin cancer (SCSC) and 3662 comparison subjects matched for age, sex, race, residence area, and length of membership. Patients were included in the study if they had no prior history of cancer, and received at least one multiphasic health checkup and questionnaire (MHC). Patients were followed for subsequent invasive cancer up to 24 years, with a mean follow-up time of 7.8 years.Results: SCSC patients had a significantly greater risk [adjusted for body mass index (BMI) and education] for subsequent cancer overall (excluding non-melanoma skin cancer) [risk ratio (RR) = 1.4, 95% confidence interval (CI) = 1.2-1.6], and for basal cell skin cancer (RR = 13.8, 95% CI = 8.8-21.9), digestive (RR = 1.6, 95% CI = 1.1-2.4), and genitourinary cancers (RR = 1.5, 95% CI = 1.0-2.0). An increased, but not statistically significant, adjusted risk (RR > or = 1.4) was also observed for lip, oral cavity, and pharynx cancer (RR = 3.9, 95% CI = 0.6-25.0); non-cutaneous squamous cell cancer (RR = 1.9, 95% CI = 0.9-4.4); and respiratory and intrathoracic cancer (RR = 1.4, 95% CI = 0.8-2.6). The addition of alcohol consumption, combined occupational exposure, marital status, and smoking history to the multivariate model did not materially change any significant positive associations with SCSC.Conclusions: Our results suggest that patients diagnosed with SCSC may be at an increased risk of subsequent cancer at many sites, although several estimated risk estimates were within the limits of chance given no true association. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: To examine the association between exposure to environmental tobacco smoke (ETS) and demographic, lifestyle, occupational characteristics and self reported health conditions. DESIGN: Cross sectional study, using data from multiphasic health checkups between 1979 and 1985. SETTING: Large health plan in Northern California, USA. PARTICIPANTS: 16 524 men aged 15-89 years and 26 197 women aged 15-105 years who never smoked. RESULTS: Sixty eight per cent of men and 64 per cent of women reported any current ETS exposure (at home, in small spaces other than home or in large indoor areas). The exposure time from all three sources of ETS exposure correlated negatively with age. Men and women reporting high level ETS exposure were more likely to be black and never married or separated/divorced, to have no college or partial college education, to consume three alcoholic drink/day or more and to report exposure to several occupational hazards. Consistent independent relations across sexes were found between any current exposure to ETS and a positive history of hay fever/asthma (odds ratio (OR)=1.22 in men, 1.14 in women), hearing loss (OR=1.30 in men, 1.27 in women), severe headache (OR=1.22 in men, 1.17 in women), and cold/flu symptoms (OR=1.52 in men, 1.57 in women). Any current ETS exposure was also associated with chronic cough (OR=1.22) in men and with heart disease (OR=1.10) in women. Self reported stroke was inversely associated with any current ETS exposure in men (OR=0.27). No associations were noted for cancer or tumour and for migraine. CONCLUSION: ETS exposure correlated with several personal characteristics potentially associated with adverse health outcomes. Although the study design precluded causal inference, ETS exposure was associated with several self reported acute and chronic medical conditions. [ABSTRACT FROM AUTHOR]

Background: Barbiturates, particularly phenobarbital, have been shown to be a tumour promoter in animal experiments and were found to be associated with increased risk of lung cancer in our cohort follow-up study to screen pharmaceuticals for possible carcinogenic effects. Sixteen more years of follow-up have accumulated permitting a more detailed evaluation of this association.Methods: In all, 10,213 subscribers of the Kaiser Permanente Medical Care Program who received barbiturates between 1969 and 1973 from its San Francisco pharmacy were followed up through 1992 and their incidence of lung cancer at biennial intervals was compared with what was expected based on the experience of the entire pharmacy cohort (143,594). Smoking-habit data were available on about half of the barbiturate users and were used to adjust for cigarette smoking in both the observed/expected analysis and in Cox proportional hazards analysis.Results: The initially elevated standard morbidity ratio of 1.55 (95% CI: 1.25-1.91) with 3-7 years of follow-up gradually decreased and stabilized at about 1.3 after 11-15 years of follow-up. This trend for diminishing relative risk over time was more pronounced among the never smokers but their initial excess risk was not statistically significant due to small numbers. A dose-response trend was observed, based on the number of prescriptions dispensed. Analytical control for cigarette smoking reduced but did not eliminate either the association or the dose-response trend. Most of the barbiturate-associated cases in never smokers were women and the predominant histological type was adenocarcinoma.Conclusions: These findings from up to 23 years of follow-up are not conclusive because of the continuing small number of never smokers who developed lung cancer. However, they strengthen and refine previous observations of a barbiturate-lung cancer association, which is probably not fully explained by confounding by cigarette smoking. The diminution of excess risk over time is consistent with a tumour promoter effect. Findings among the never smokers suggest that this possible effect may be greatest on adenocarcinomas in women. [ABSTRACT FROM AUTHOR]

Purpose: C-reactive protein (CRP), Chlamydia pneumonia, Helicobacter pylori, and cytomegalovirus (CMV) have each been associated with atherosclerosis. We assessed how infection and CRP related to risk for subsequent myocardial infarction (MI).Methods: Using a nested case-control design, we assessed how these factors independently and jointly affected risk for myocardial infarction (MI). Cases of first MI (N = 121) were identified from among participants in a multiphasic health check-up cohort. Controls without MI (N = 204) were matched to cases by gender, age, race, and date of serum collection. Sera collected at enrollment were tested for antibodies to infection and for CRP.Results: In multivariate analysis (mean follow-up of 5.1 years), CRP was associated with MI only in subjects older than 51 years (p = 0.004). Although H. pylori infection increased risk for MI, this association was modest (OR = 1.90, 95% CI = 0.97-3.71) and was not evident in non-smokers or when adjusted for education. No association between C. pneumoniae or cytomegalovirus and MI was observed, nor was the association between CRP and MI explained by these infections.Conclusions: Elevated CRP is a risk factor for subsequent MI in older individuals. The relationship between Hp and MI may be due to confounding or co-linearity with socioeconomic status. [ABSTRACT FROM AUTHOR]

International comparison data suggest that wine may be more protective against coronary artery disease than beer or liquor. There are potentially protective antioxidants in wine, especially red wine. However, prospective population studies suggest that each beverage type may reduce coronary risk. The role of alcoholic beverage choice in coronary risk remains unresolved. We performed a prospective study of coronary disease hospitalizations among 128,934 adult members of a Northern California prepaid comprehensive health care program. Alcohol data were supplied at health examinations. Using Cox proportional-hazards models with 9 covariates, analyses were performed of the roles of each major beverage type (wine, beer, and liquor) and of drinking only table wine (red, white, or both). Generally, coronary risk traits were most favorable for wine drinkers and least favorable for liquor drinkers. Among 3,931 persons hospitalized for coronary disease, total alcohol drinking was inversely related to risk in both sexes. Uncontrolled for total alcohol, each beverage type showed evidence for coronary protection, weakest for liquor and strongest for beer in men and wine in women. Controlled for total alcohol, these relations were much reduced, and lost statistical significance except for beer in men and both red and white wine (combined) in all persons. We conclude that (1) drinking ethyl alcohol apparently protects against coronary disease, and (2) there may be minor additional benefits associated with drinking both beer and wine, but not especially red wine. [ABSTRACT FROM AUTHOR]

Melanocortin 3 receptors (MC3R) and melanocortin 4 receptors (MC4R) are vital in regulating a variety of functions across many species. For example, the dysregulation of these receptors results in obesity and dysfunction in sexual behaviors. Only a handful of studies have mapped the expression of MC3R and MC4R mRNA across the central nervous system, with the primary focus on mice and rats. Because Syrian hamsters are valuable models for functions regulated by melanocortin receptors, our current study maps the distribution of MC3R and MC4R mRNA in the Syrian hamster telencephalon, diencephalon, and midbrain using RNAscope. We found that the expression of MC3R mRNA was lowest in the telencephalon and greatest in the diencephalon, whereas the expression of MC4R mRNA was greatest in the midbrain. A comparison of these findings to previous studies found that MC3R and MC4R expression is similar in some brain regions across species and divergent in others. In addition, our study identifies novel brain regions for the expression of MC3Rs and MC4Rs, and identifies cells that co-express bothMC3 and MC4 receptors within certain brain regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hall, Kohut-Jackson, Peyla, Friedman, Simco, Borland and Meisel.)

Context: The antipsychotic drug haloperidol has antiproliferative and growth-inhibiting properties on prostate cancer cell lines in vitro by binding the sigma 1 protein. Evidence is needed regarding a possible preventive association in men., Objective: To examine whether our epidemiologic data support an inverse association of haloperidol use with risk of prostate cancer., Design: These case-control analyses used conditional logistic regression to estimate relative risk by odds ratios (ORs) adjusting for race/ethnicity and aspects of medical care related to detection of prostate cancer. We tested 3 other commonly used antipsychotic drugs, risperidone, quetiapine, and olanzapine, for sigma 1 protein binding and inhibition of clonogenic growth of prostate cancer cells. Use of any of these by men was considered use of a comparator drug., Main Outcome Measures: 1) association of haloperidol with prostate cancer; 2) sigma 1 binding and clonogenic growth., Results: Probably owing to small numbers of haloperidol recipients, evidence of a preventive association was inconsistent, depending on the definition of long-term use. If duration of use was greater than 1 year, the odds ratio (OR) was 0.38 (95% confidence interval (CI) = 0.14-1.01) for haloperidol and 0.80 (95% CI = 0.66-0.98) for the comparator drug; if the duration of use was greater than 2 years, the OR was 0.66 (95% CI = 0.24-1.76) for haloperidol and 0.84 (95% CI = 0.66-1.08) for the comparator drug. Unlike haloperidol, risperidone, quetiapine, and olanzapine did not bind sigma 1 or inhibit clonogenic growth., Conclusion: Given the laboratory evidence, our ambiguous epidemiologic findings should encourage more epidemiologic evaluation of haloperidol use and risk of prostate cancer. Finding a negative association could be a scientific advance in prostate cancer prevention but would not be sufficient basis for recommending the prescription of haloperidol for that purpose.

Background: The effectiveness of 5-fluorouracil compared with that of imiquimod for preventing keratinocyte carcinoma is unknown., Objective: To compare the effectiveness of 5-fluorouracil and that of imiquimod in preventing keratinocyte carcinoma in a real-world practice setting., Methods: We identified 5700 subjects who filled prescriptions for 5-fluorouracil or imiquimod for treatment of actinic keratosis in 2007. An intention-to-treat analysis controlling for potential confounding variables was used to calculate 2- and 5-year cumulative risk differences for subsequent keratinocyte carcinoma overall and in field-treated areas., Results: 5-Fluorouracil was associated with a statistically significant decreased risk of any keratinocyte carcinoma compared with imiquimod (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.76-0.97), but there were no significant differences in risk by tumor subtype (for squamous cell carcinoma: aHR, 0.89; 95% CI, 0.74-1.07; for basal cell carcinoma: aHR, 0.87; 95% CI, 0.74-1.03) or site-specific keratinocyte carcinoma (aHR, 0.96; 95% CI, 0.81-1.14). There were no significant differences in 2- or 5-year cumulative risk of keratinocyte carcinoma among those treated with 5-fluorouracil versus with imiquimod., Limitations: Generalizability to other practice settings may be limited., Conclusions: Whereas 5-fluorouracil was more effective in reducing keratinocyte carcinoma risk overall, we found no differences in the short- or long-term risk of subsequent site-specific keratinocyte carcinoma in a real-world practice setting., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Context: Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database., Objective: To update these epidemiologic analyses with 7.5 more years of follow-up., Design: Case-control analyses using conditional logistic regression to estimate relative risk by odds ratios using the prior collaboration's criteria for identifying positive drug-cancer associations and our more stringent criteria requiring stronger association, lower p values, and evidence of dose response. New associations were reanalyzed with additional control for limited measures of smoking and alcohol use., Main Outcome Measures: Gabapentin-cancer associations., Results: No previously found associations met our stringent criteria, but cancers of the mouth/pharynx, esophagus, liver, and vagina did. All odds ratios for 3 or more and 8 or more prescriptions were moderately reduced by control for smoking and alcohol. Substantial elevations of risk of mouth/pharynx, liver, and vaginal cancers were associated with only 1 prescription dispensed. Sensitivity analyses aimed at possible confounding and other biases did not change our conclusions but did reveal a markedly increased risk of vaginal cancer in gabapentin users with epilepsy compared with users without., Conclusion: The reduced magnitude of relative risk with control for smoking and alcohol use suggests confounding by known risk factors. Biologically implausible elevated risk from just 1 prescription suggests confounding by indication. Either or both of these concerns applies to each of the 4 cancer sites associated with gabapentin use. Updated analyses show little if any evidence for carcinogenic effects of gabapentin.

Background: Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown., Objectives: To examine the association between AD use and cSCC risk among a cohort of non-Hispanic white individuals with hypertension enrolled in a comprehensive integrated healthcare delivery system in northern California (n = 28 357)., Methods: Electronic pharmacy data were used to determine exposure to ADs, which were classified as photosensitizing, nonphotosensitizing or unknown, based on published literature. We identified patients who developed a cSCC during follow-up (n = 3010). We used Cox modelling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Covariates included age, sex, smoking, comorbidities, history of cSCC and actinic keratosis, survey year, healthcare utilization, length of health plan membership and history of photosensitizing AD use., Results: Compared with nonuse of ADs, risk of cSCC was increased with ever having used photosensitizing ADs (aHR = 1·17, 95% CI 1·07-1·28) and ever having used ADs of unknown photosensitizing potential (aHR = 1·11, 95% CI 1·02-1·20), whereas no association was seen with ever having used nonphotosensitizing ADs (aHR = 0·99; 95% CI 0·91-1·07). Additionally, there was a modest increased risk with an increased number of prescriptions for photosensitizing ADs (aHR = 1·12, 95% CI 1·02-1·24; aHR = 1·19, 95% CI 1·06-1·34; aHR = 1·41, 95% CI 1·20-1·67 for one to seven, eight to 15 and ≥ 16 fills, respectively)., Conclusions: These findings provide moderate support for an increased cSCC risk among individuals treated with photosensitizing ADs., (© 2018 British Association of Dermatologists.)

Background: The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting., Objective: We compared the effectiveness of 5-fluorouracil and imiquimod in reducing risk for subsequent AKs in a large, integrated health care delivery system in northern California., Methods: In this cohort study, we identified adult health plan members who had an AK diagnosed in 2007 and who subsequently filled a prescription for 5-fluorouracil or imiquimod (N = 5700). We followed subjects for subsequent AKs identified by the International Classification of Diseases codes and estimated the 2-year (short-term) and 5-year (long-term) differences in cumulative risk while controlling for potential confounding by pretreatment variables., Results: 5-Fluorouracil reduced the short-term incidence of subsequent AKs (cumulative risk difference -4.54% [95% confidence interval, -7.91% to -1.17%]), but there was no statistically significant evidence of a long-term decreased risk (cumulative risk difference -1.43% [95% confidence interval, -3.43% to 0.05%]) compared with that with imiquimod., Limitations: This is a retrospective study with limited ascertainment of all relevant potential confounding variables., Conclusion: We found that 5-fluorouracil appeared to be significantly more effective than imiquimod in the short-term, but not long-term, prevention of subsequent AKs., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer., Objectives: To study the association between use of hydrochlorothiazide and squamous cell carcinoma of the lip., Methods: We conducted a case-control study using Danish nationwide registry data. From the Cancer Registry (2004-2012), we identified 633 case patients with squamous cell carcinoma (SCC) of the lip and matched them to 63 067 population controls using a risk-set sampling strategy. Hydrochlorothiazide use (1995-2012) was obtained from the Prescription Registry and defined according to cumulative use. Applying conditional logistic regression, we calculated odds ratios (ORs) for SCC lip cancer associated with hydrochlorothiazide use, adjusting for predefined potential confounders obtained from demographic, prescription and patient registries., Results: Ever-use of hydrochlorothiazide was associated with an adjusted OR for SCC lip cancer of 2.1 (95% confidence interval (CI): 1.7-2.6), increasing to 3.9 (95%CI: 3.0-4.9) for high use (≥25 000 mg). There was a clear dose-response effect (P < 0.001), with the highest cumulative dose category of hydrochlorothiazide (≥100 000 mg) presenting an OR of 7.7 (95%CI: 5.7-10.5). No association with lip cancer was seen with use of other diuretics or nondiuretic antihypertensives. Assuming causality, we estimated that 11% of the SCC lip cancer cases could be attributed to hydrochlorothiazide use., Conclusions: Hydrochlorothiazide use is strongly associated with an increased risk of lip cancer., (© 2017 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Purpose: To supplement published cohort data about incident cancer in Asian Americans (Asians) including risk of specific Asian ethnic groups., Methods: A cohort study in 124,193 persons (13,344 Asians) with baseline examination data in 1978-1985 used Cox proportional hazards models with seven covariates to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs)., Results: Through 2012 cancer was diagnosed in 18,687 persons including 1,522 Asians. Compared to Whites, the HR (CIs) for any cancer in Asians was 0.8 (0.7-0.9, p < 0.001). Lower Asian risk was stronger for men (HR = 0.7, p < 0.001) than for women (HR = 0.9, p = 0.003). Lower Asian vs. White risks with p < 0.05 were found for cancers of the upper airway digestive area, hematologic malignancies, melanoma, and cancers of the prostate, bladder, and brain. Melanoma contributed substantially to lower Asian risk, especially in women. HRs for specific Asian groups versus Whites follow: Chinese = 0.9 (p < 0.001), Japanese = 0.9 (p = 0.01), Filipinos = 0.8 (p < 0.001), South Asians = 0.5 (p < 0.001), and Other Asians = 0.7 (p = 0.006). Both South Asian men and women had lower risk than Whites, and South Asians had lower risk than any other racial/ethnic group., Conclusions: Asians had lower cancer risk than Whites, due to lower risk of several cancer types. Each Asian ethnic group had lower risk than Whites with South Asians at the lowest risk.

A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects enrolled in Kaiser Permanente Northern California. Addressing confounding by indication by restricting subjects to those with elevated cholesterol greatly attenuated the negative association; eg, the multivariable-adjusted odds ratio (OR) rose from 0.41 (95% confidence interval [CI] = 0.35 to 0.49) to 0.87 (95% CI = 0.55 to 1.39) for receipt of 18 or more prescriptions. Confounding by contraindication was addressed by controlling for degree of abnormality of liver function tests, alanine or aspartate transaminase, measured within one year of the elevated cholesterol and strongly related to risk. The negative association of statins disappeared for all numbers of prescriptions received, with an odds ratio of 1.21 (95% CI = 0.53 to 2.75) for 18 or more prescriptions. Findings cast doubt on the causality of the frequently observed preventive association., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The authors studied incident cancer risk from 1978 to 1985 and through follow-up in 2012 relative to light-to-moderate and heavy drinking and to the choice of alcoholic beverage in a cohort of 124,193 persons. With lifelong abstainers as referent, heavy drinking (≥ 3 drinks per day) was associated with increased risk of 5 cancer types: upper airway/digestive tract, lung, female breast, colorectal, and melanoma, with light-to-moderate drinking related to all but lung cancer.

Purpose: There is compelling evidence that heavy alcohol drinking is related to increased risk of several cancer types, but the relationship of light-moderate drinking is less clear. We explored the role of inferred underreporting among light-moderate drinkers on the association between alcohol intake and cancer risk., Methods: In a cohort of 127,176 persons, we studied risk of any cancer, a composite of five alcohol-associated cancer types, and female breast cancer. Alcohol intake was reported at baseline health examinations, and 14,880 persons were subsequently diagnosed with cancer. Cox proportional hazard models were controlled for seven covariates. Based on other computer-stored information about alcohol habits, we stratified subjects into 18.4 % (23,363) suspected of underreporting, 46.5 % (59,173) not suspected of underreporting, and 35.1 % (44,640) of unsure underreporting status., Results: Persons reporting light-moderate drinking had increased cancer risk in this cohort. For example, the hazard ratios (95 % confidence intervals) for risk of any cancer were 1.10 (1.04-1.17) at <1 drink per day and 1.15 (1.08-1.23) at 1-2 drinks per day. Increased risk of cancer was concentrated in the stratum suspected of underreporting. For example, among persons reporting 1-2 drinks per day risk of any cancer was 1.33 (1.21-1.45) among those suspected of underreporting, 0.98 (0.87-1.09) among those not suspected, and 1.20 (1.10-1.31) among those of unsure status. These disparities were similar for the alcohol-related composite and for breast cancer., Conclusions: We conclude that the apparent increased risk of cancer among light-moderate drinkers may be substantially due to underreporting of intake.

Purpose: Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs., Methods: In the Kaiser Permanente Medical Care Program in Northern California, 906 men with testicular cancer diagnosed August 1996-December 2010 were compared with 38,253 matched controls with race/ethnicity recorded regarding receipt of antidepressant drugs at least 2 years before diagnosis or control index date. Analyses emphasized duration of use and histological subgroups., Results: With control for race/ethnicity and use of other antidepressant drugs, odds ratios (OR) and 95 % confidence intervals (CI) for associations with testicular cancer were as follows: fluoxetine 1.22 (0.88-1.71), paroxetine 1.19 (0.78-1.83), and 1.21 (0.92-1.58) for all serotonin reuptake inhibitors. There was no statistically significant association with risk of all testicular cancers or their histological subtypes for any individual drug or for tricyclics or all antidepressants combined except for citalopram with all testicular cancers 2.55 (1.43-4.52) and those of mixed histology 4.36 (1.50-12.68) and nefazodone with embryonal cancers 9.79 (1.85-51.81). These could readily be chance findings in the context of the many analyses that were performed. Duration of use was not associated with risk of the drugs and drug groups with sufficient numbers of exposed cases for analysis., Conclusions: We found little evidence to support a testicular carcinogenic effect of fluoxetine, paroxetine, or other antidepressant drugs, but a weakly positive association is not ruled out. The signals in prior screening may have been due to chance and/or uncontrolled confounding.

Objective: To study risk factors for cell types of lung cancer., Methods: Cohort study of 126,293 persons with 1852 subjects with incident cancer. We performed Cox proportional hazards models (8 covariates) to estimate risk of the 4 most numerous specific cell types: adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and bronchioloalveolar carcinoma., Results: Smoking 1 or more cigarette packs per day was a powerful predictor (p < 0.0001) of all cell types, with hazard ratios ranging from 5.8 for bronchioloalveolar to 62.7 for squamous cell carcinoma. Other hazard ratio ranges included male/female from 0.6 (bronchioloalveolar, p < 0.05) to 2.0 (squamous, p < 0.001); black/white from 0.8 (small cell, p < 0.05) to 1.7 (squamous, p < 0.001); Asian/white from 0.8 (small cell) to 1.9 (bronchioloalveolar); and alcohol intake of 3 or more drinks per day from 1.0 (squamous) to 1.5 (adenocarcinoma, p < 0.01). College graduation and increasing body mass index were inversely related to risk of several cell types. Noteworthy sex-specific associations included increased risk of Asian vs white women for adenocarcinoma, squamous cell carcinoma and bronchioloalveolar carcinoma and substantially increased risk of adenocarcinoma in women with alcohol intake of 3 or more drinks per day., Conclusions: These risk factor disparities for lung cancer cell types presumably reflect biologic differences. Future investigation may contribute to increased understanding of tumorigenesis and optimal treatment.

Background: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs., Methods: In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the β-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking., Results: At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82 (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08)., Conclusion: These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.

Purpose: High doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care program and followed up nominally significant associations in a UK primary care database., Methods: In the US Kaiser Permanente Northern California (KPNC) health system, we performed nested case-control analyses of gabapentin and 55 cancer sites and all cancers combined using conditional logistic regression. Up to 10 controls were matched to each case on year of birth, sex, and year of cohort entry. No other covariates were included in models. Only dispensings for gabapentin 2 years or more before index date were considered. Nominally significant associations with an OR > 1.00 and p < 0.05 for three or more dispensings versus no dispensings were followed up by similar nested case-control analyses in the UK General Practice Research Database (GPRD), adjusting for potential indications for gabapentin and risk factors for the specific cancers., Results: The following analyses had OR > 1.00 and p < 0.05 for three or more dispensings of gabapentin versus no dispensing (2-year lag) in KPNC and were also examined in the GPRD: all cancers, breast, lung and bronchus, urinary bladder, kidney/renal pelvis, stomach, anus/anal canal/anorectum, penis, and other nervous system. These cancers were not statistically significantly associated with gabapentin in the GPRD case-control studies (2-year lag). The GPRD and KPNC studies did not identify a statistically significant increased risk of pancreatic cancer with more than two prescriptions of gabapentin in the 2-year lagged analyses., Conclusions: The epidemiological data in a US cohort with up to 12 years of follow-up and a UK cohort with up to 15 years of follow-up do not support a carcinogenic effect of gabapentin use. However, the confidence intervals for some analyses were wide, and an important effect cannot be confidently excluded., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Laboratory and epidemiologic studies suggest that certain dietary supplements may alter risk of cutaneous squamous cell carcinoma (SCC)., Objective: We sought to examine the association between supplement use and SCC risk., Methods: Cases (n = 415) were defined as Kaiser Permanente Northern California members with a pathology-verified SCC in 2004 and control subjects (n = 415) were age-, sex-, and race-matched members with no history of skin cancer. Supplement use and SCC risk factors were ascertained by questionnaire. Associations of SCC with use of multivitamins; vitamins A, C, D, and E; and grape seed extract were estimated as odds ratios and 95% confidence intervals using conditional logistic regression. Models were adjusted for SCC risk factors and other supplement use., Results: Grape seed extract users had a significantly decreased risk of cutaneous SCC (adjusted odds ratio 0.26, confidence interval 0.08-0.89, P = .031). Multivitamin use was associated with a borderline significant reduction in SCC risk (adjusted odds ratio 0.71, confidence interval 0.51-1.00, P = .049). Use of vitamins A, C, D, and E was not associated with SCC risk., Limitations: The data may be prone to recall and selection bias because of the case-control design. No information was obtained on dose or duration of supplement use., Conclusions: Use of grape seed extract may be associated with a decreased risk of cutaneous SCC. The other supplements included in our study did not reveal clear associations with SCC risk., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120 mm Hg was associated with a higher risk of mortality compared with the referent group (140-159 mm Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

Laboratory and epidemiologic studies suggest a protective effect of tea consumption on risk of cutaneous squamous cell carcinoma (SCC). We designed a case-control study to examine the association between putative protective exposures, including tea consumption, and SCC risk using a large health maintenance organization population. Cases (n=415) were defined as Kaiser Permanente Northern California (KPNC) members with a pathology-verified SCC in 2004 and controls (n=415) were age-, gender-, and race-matched members with no previous history of skin cancer. Tea consumption and SCC risk factors were ascertained by questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression to estimate the association of SCC with regular use, as well as dose and duration of tea consumption. Risk factor adjusted models included education, smoking, hair and eye color, skin type, family history of skin cancer, and history of freckling, sunburns, sun exposure, and tanning bed use. Adjusted analyses showed no reduction in SCC risk with regular consumption of tea (OR=1.11, 95% CI: 0.81-1.54). Examining duration, dose, and combined duration and dose exposure variables did not alter findings. We found no evidence that tea consumption was associated with cutaneous SCC risk., (Copyright © 2011, Taylor & Francis Group, LLC)

Background/aims: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin use and risk for breast cancer, stratified by HR status. We conducted a large case-control study within Kaiser Permanente of Northern California (KPNC) to determine whether chronic use of lipophilic statins is associated with decreased risk of HR-negative breast cancer or other breast cancer subtypes., Methods: We identified 22,488 breast cancer cases diagnosed from 1997 to 2007, and 224,860 controls matched to cases based upon birth year and duration of KPNC pharmacy coverage. Use of lipophilic statins was ascertained using the comprehensive electronic pharmacy records of KPNC., Results: We found no association between lipophilic statin use (≥2 y versus never) and overall breast cancer risk (odds ratio(adj), 1.02; 95% CI, 0.97-1.08) in conditional logistic regression models adjusted for oral contraceptive and hormone therapy use. Women who used lipophilic statins did not have a decreased risk of HR-negative breast cancer (odds ratio(adj), 0.98; 95% CI, 0.84-1.14) nor altered risk of HR-positive disease (odds ratio(adj), 1.03; 95% CI, 0.97-1.10). Furthermore, lipophilic statin use was not associated with risk of any of the intrinsic subtypes, luminal A, luminal B, human epidermal growth factor receptor 2 positive/estrogen receptor negative, or triple negative., Conclusions: Our results do not support an association of lipophilic statin use with the risk for breast cancer in general or with risks of HR-negative or other breast cancer subtypes specifically., Impact: These findings do not confirm previous reports of a possible preventive association., (©2010 AACR.)

We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and basal cell carcinoma (BCC) risk in a nested case-control study at Kaiser Permanente Northern California (KPNC). A total of 220 case patients with BCC diagnosed after serum collection were matched to 220 control subjects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression. Fully adjusted models included body mass index (BMI), smoking, education, sun-exposure variables, X-ray exposure, and personal history of cancer. For each measure of serum 25(OH)D (continuous, clinically relevant tertiles, quintiles), we found an increased risk of BCC in unadjusted models (OR=1.03, 95% CI 1.00-1.05, P<0.05; OR=3.98, 95% CI: 1.31-12.31, deficient vs. sufficient, test for trend P-value <0.01; OR=2.32, 95% CI: 1.20-4.50, 1st vs. 5th quintile, test for trend P-value 0.03). In fully adjusted models, the values attenuated slightly (OR=1.02, 95% CI 1.00-1.05, P<0.05; OR=3.61, 95% CI: 1.00-13.10, deficient vs. sufficient, t-trend P=0.03; OR=2.09 1st vs. 5th quintile, 95% CI: 0.95-4.58, t-trend P=0.11). Our findings suggest that higher prediagnostic serum 25(OH)D levels may be associated with increased risk of subsequent BCC. Further studies to evaluate the effect of sun exposure on BCC and serum 25(OH)D levels may be warranted.

Objective: To examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and cutaneous squamous cell carcinoma (SCC)., Design: Retrospective case-control study., Setting: Kaiser Permanente Northern California (KPNC), a large population based-health maintenance organization., Patients: Random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and 415 age-, sex-, and race-matched controls with no history of skin cancer., Main Exposure Measure: Self-reported NSAID use in the 10 years prior to baseline. Use of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the association of SCC with regular use, dose, and duration of exposure to the different NSAID types. Information on pharmacy-dispensed NSAIDs was also examined to assess its association with SCC risk. Models were adjusted for all ascertained SCC risk factors (fully adjusted model) and only those variables associated with both SCC risk and NSAID use (parsimonious model)., Results: Fully adjusted analyses showed no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96-1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining duration and dose of NSAID exposure did not appreciably change results. An analysis using the parsimonious model showed similar results. The data on pharmacy-dispensed NSAIDs also showed no association with SCC risk., Conclusion: Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk.

Recently, a population-based case-control study observed a 60% increased odds ratio (OR) for cutaneous squamous cell carcinoma (SCC) among women who had ever used oral contraceptives (OCs) compared with non users (95% confidence interval (CI) = 1.0-2.5). To further characterize the putative association between OC use and SCC risk, we conducted a nested case-control study using a large retrospective cohort of 111,521 Kaiser Permanente Northern California members. Multivariable conditional logistic regression was used to estimate ORs and CIs adjusting for known and hypothesized SCC risk factors. Pre-diagnostic OC use was associated with a statistically significant increased OR for SCC in univariate analysis (OR = 2.4, CI = 1.2-4.8), with borderline statistical significance in multivariable analysis (CI = 2.0, CI = 0.91-4.5). Given the high incidence of SCC in the general population and the prevalent use of OCs among women in the United States, there is a need for more large, carefully designed epidemiologic studies to determine whether the observed association between OC use and SCC can be replicated and to better understand the etiologic basis of an association if one exists.

Objective: To screen 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 2 years between drug dispensing and cancer. Positive associations entailed a relative risk 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 nonHodgkin 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.

Thorough review by the International Agency for Research on Cancer (IARC) has resulted in classifying many substances, including pharmaceuticals, as probably or possibly carcinogenic to humans, based on experiments on animals or limited data on humans. We evaluated 9 such pharmaceuticals for evidence of carcinogenicity in patients receiving them in a large medical care program with automated pharmacy records and a cancer registry. Nested case-control analyses were performed in a cohort of 6.5 million subscribers with up to 12 years of follow-up, focusing on cancer sites suggested by previous evidence and other sites with odds ratio of at least 1.50, p < 0.01 and some evidence of dose-response. Unmeasured confounding was estimated in sensitivity analyses. We found some supportive evidence for carcinogenicity of griseofulvin, metronidazole and phenytoin and for the known carcinogen, cyclophosphamide, which was added for validation of our data and analyses. Findings for chloramphenicol, iron-dextran complex, phenoxybenzamine and phenobarbital were essentially non-contributory. Confounding by cigarette smoking and prior thyroid disease could account, respectively, for associations of oxazepam with lung cancer and propylthiouracil with thyroid cancer. Although not definitive, these findings should be considered in the evaluations of these pharmaceuticals., ((c) 2009 UICC.)

Purpose: Limited data suggest that alcohol drinking may have an inverse relation to risk of non-Hodgkin's lymphoma (NHL). Prospective data about alcohol, NHL, and other hematologic malignancies (HM) are sparse., Methods: We carried out a cohort study in a multiethnic population of 126,293 adults who supplied baseline information at health examinations. There were subsequent HM diagnoses in 1244 persons. We used Cox proportional hazards models with seven covariates. The role of beverage types was studied by comparing groups with preponderant choices and by studying the role of frequency of drinking beverage types., Results: Using lifelong abstainers plus infrequent drinkers as referent, adjusted relative risks (95% confidence intervals) for HM follow: less than one drink per day=1.0 (0.9-1.2), one to two drinks per day=0.9 (0.7-1.0), greater than three drinks per day=0.7 (0.6-0.9, p=0.008). For 673 NHL these were 1.2 (1.0-1.5), 0.9 (0.7-1.2), and 0.9 (0.6-1.2). Persons reporting greater than three drinks/day had inverse relations to lymphocytic (n= 146) and myelocytic (n= 169) leukemias, with relative risk of 0.5 (0.2-1.0, p<0.05) for each. No major independent relation was seen for choice of wine, liquor, or beer., Conclusions: Alcohol drinking is associated with slightly lower risk of HM, due largely to inverse relations to lymphocytic and myelocytic leukemia.

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 2 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.