Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma.

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.

Hydrochlorothiazide use is strongly associated with risk of lip cancer.

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.

Systolic blood pressure and mortality in prevalent haemodialysis patients in the HEMO study.

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.

Exposure to environmental tobacco smoke: association with personal characteristics and self reported health conditions.

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.

Cohort study of thyroid cancer in a San Francisco Bay area population.

Using data from a large health plan, we performed a cohort study of thyroid cancer among 204,964 persons (aged 10--89 at baseline in 1964--1973, 54% female) followed for a median of 20 years. There were 196 incident thyroid cancers (73 in men, 123 in women). Risk was independently and positively related to female gender [relative risk (RR) = 1.56, 95% confidence interval (CI) = 1.12--2.19], Asian race (RR = 2.86, 95% CI = 1.76--4.65), completed college or post-graduate education (RR = 1.76, 95% CI = 1.20--2.59), history of goiter (RR = 3.36, 95% CI = 1.82--6.20), radiation of the neck region (RR = 2.33, 95% CI = 1.28--4.23) and family history of thyroid disease (RR = 2.18, 95% CI = 1.17--4.05). An inverse association was found for black race (RR = 0.55, 95% CI = 0.33--0.91). Cigarette smoking, alcohol consumption, personal history of hyperthyroidism, hypothyroidism, overweight or obesity, weight gain since age 20, height, occupational exposures, reproductive factors, oral contraceptives and hormone use did not show statistically significant relations to thyroid cancer. These results provide further evidence for a role of female gender, radiation, goiter, Asian race, high educational attainment and family history of thyroid disease in the etiology of thyroid cancer.

Concomitant medication use in postmenopausal women using estrogen therapy.

OBJECTIVE: To determine whether long-term postmenopausal estrogen therapy is associated with use of other prescription medications. METHODS: Using computer pharmacy records from 1969 to 1973 for members of the Kaiser Permanente Medical Care Program in San Francisco, we identified the 215 most commonly used prescription medications in the pharmacy database and recorded their use by 232 postmenopausal long-term estrogen users and by 222 postmenopausal age-matched nonusers. These medications were grouped into 39 therapeutic classes. Classes of medications used by estrogen users and nonusers were compared. RESULTS: A statistically significant difference in use was seen for 21 of the 39 medication classes; of these 21 classes, 20 (95%) were used more frequently and 1 less frequently by estrogen users. Differences between estrogen users and nonusers were greatest for thyroid hormone preparations (estrogen user/nonuser multivariate odds ratio = 25.6, 95% confidence interval 5.9-112) and antimigraine preparations (11 recipients among estrogen users, none among nonusers). Postmenopausal women using estrogen were more likely than nonusers to use additional medications. CONCLUSION: Greater use of certain prescription medications by estrogen users than by nonusers should be considered in studying the health effects of estrogen replacement therapy.

Colon cancer screening, lifestyle, and risk of colon cancer.

OBJECTIVES: Sigmoidoscopy screening and fecal occult blood (FOB) tests have been demonstrated as effective ways to reduce mortality from colorectal cancer. However, most studies of colorectal cancer screening and cancer mortality have not taken into consideration lifestyle factors that could account for the observed associations. The purpose of this study was to determine the association between screening and incidence of colon cancer, taking into consideration important lifestyle factors. METHODS: We estimated the association between screening and colon cancer after taking into consideration health and lifestyle factors using data obtained as part of population-based case-control study of incident colon cancers. RESULTS: Sigmoidoscopy screening, especially as part of a checkup, was protective against incident colon cancer in both men (OR 0.56, 95% CI 0.44-0.77) and women (OR 0.53, 95% CI 0.33-0.77) after adjusting for other risk factors for colon cancer. For men, associations were stronger for distal tumors (OR 0.48, 95% CI 0.31-0.71) than for proximal tumors (OR 0.67, 95% CI 0.45-1.11). We did not observe significant associations between FOB test and colon cancer. Differences in characteristics between those who were screened and not screened were also observed. Men were more likely to report having a sigmoidoscopy as part of a checkup than were women, as were people with higher levels of education. People who reported having a sigmoidoscopy as part of a checkup also reported eating diets lower in fat and higher in fiber, folate, and vegetables. Men were more likely to report higher levels of physical activity, and women were more likely to report taking hormone replacement therapy (HRT) if they also reported a sigmoidoscopy. Both men and women who reported a sigmoidoscopy for screening purposes were more likely to have a family history of colorectal cancer. CONCLUSIONS: These data provide additional support for the benefits of having a screening sigmoidoscopy. The associations between screening sigmoidoscopy and colon cancer do not appear to be the result of lifestyle factors.

Association of basal cell skin cancers with other cancers (United States).

BACKGROUND: Persons with basal cell skin cancer (BCSC) have shown increased risk of developing cancer at several other sites. METHODS: We identified 3164 persons with BCSC and 15,730 comparison subjects matched for age, sex, race, residence area and length of membership in a health maintenance organization. RESULTS: In retrospective follow-up for up to 24 years (mean 11.3 years), BCSC patients experienced statistically significant increases in the incidence of all cancer (relative risk [RR] = 1.2, 95% confidence interval [CI] = 1.1-1.4) lung cancer (RR = 1.4, CI = 1.0-1.8) and melanoma (RR = 2.2, CI = 1.6-3.0). Women experienced significantly increased risk for all cancer, lung cancer, melanoma and thyroid cancer, increases of borderline significance in breast cancer, non-Hodgkin's lymphoma and leukemia, and increased pre-existing bladder cancer. Men showed statistically significant increases in all cancer, melanoma, and kidney cancers, and mouth and throat cancers. Multivariate analysis incorporating available risk factor data did not weaken positive associations with BCSC except slightly for melanoma and for bladder cancer in women. Other previously reported associations were not confirmed. CONCLUSION: Periodic skin examinations appear well justified after removal of BCSC to detect new skin cancers including melanoma. Given the relatively weak, unexplained associations of BCSC with internal cancers, the costs vs. benefits of extra efforts to detect the latter still need to be determined.

Body size, age at shaving initiation, and prostate cancer in a large, multiracial cohort.

BACKGROUND: The purpose of this study was to examine the potential relationship between body size, self-reported age at initiation of shaving, and subsequent risk of prostate cancer in a large, racially diverse cohort of men followed for up to 32 years. METHODS: The study population included 70,712 male subscribers to the Kaiser Permanente Medical Care Program who had received a multiphasic health checkup between 1964-1973. This general health checkup consisted of a number of laboratory tests and physical measurements, as well as a self-completed health questionnaire that included a request for men to record the age when they began shaving. Subjects were followed for the development of prostate cancer, using the local tumor registry. Cox regression was used to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: Altogether, 2, 079 men in the study cohort were diagnosed with prostate cancer. There was a very strong positive association between prostate cancer risk and birth cohort. After adjusting for race, age, and birth year, there was no association between height, weight, body mass index, or several other anthropometric measures and prostate cancer risk in the full cohort. There was a suggestion of a very weak positive association between height and prostate cancer risk among white men. There also was no overall association between age at shaving initiation and prostate cancer risk, although nonwhite men who started shaving at a young age (

Cimetidine use and risk of breast, prostate, and other cancers.

Purpose - The study was conducted to examine whether use of cimetidine is associated with the risk of cancer, with special attention to cancers of the breast and prostate because cimetidine increases estradiol levels and interferes with androgen binding. Methods - Individuals who received a prescription of cimetidine were identified from two computerized pharmacy databases of medications dispensed at Northern California Kaiser Permanente between 1982 and 1987. Users of ranitidine, a histamine-2 receptor antagonist that does not appear to influence estrogen levels or androgen binding, and non-users of either cimetidine or ranitidine, were also identified from these databases. Study subjects were followed through December 1995 for new diagnoses of cancer. Cox regression was used to estimate relative risks of cancer associated with use of cimetidine and ranitidine. Non-users of cimetidine and ranitidine were the referent group for all analyses. Result - While there were very modest increases and decreases in risk for some cancer sites among cimetidine users, most were within the limits of chance given no true association. Furthermore, similar risks of these cancers were also observed among ranitidine users. Conclusions - Although our results do not support an association between cancer risk and cimetidine use, it is one of the most widely prescribed drugs in the US and may now be purchased over-the-counter. The potential effect of cimetidine on risk of cancer, especially those that are hormone-related, should continue to be monitored, preferably in larger study populations. Copyright (c) 2000 John Wiley & Sons, Ltd.

Spousal concordance for cancer incidence: A cohort study.

BACKGROUND: Because married couples share at least their home environment, spousal aggregation of cancer might provide clues to unsuspected etiologic factors. The authors sought to measure the concordance of cancer occurrence in married couples and explore factors that might explain greater-than-expected concordance. METHODS: The authors identified 25,670 cancer-free married couples in northern California who were followed for up to 31 years for the development of cancer. In Cox proportional hazards analysis, the development of cancer in a spouse was treated as a time-dependent, independent variable, and spouse-with/spouse-without risk ratios were determined, controlling for age and gender. For selected concordant espoused pairs, additional explanatory information was sought in their medical records. RESULTS: There was no excess concordance for all cancers combined; the spouse-with/spouse-without risk ratio was 0.97 (95% confidence interval, 0.90-1.05). Statistically significant husband-wife associations were found only for cancer of the tongue and stomach and for non-Hodgkin lymphoma. Except for cancer of the penis/endometrium and testis/vulva, based on one couple with each combination, gender specific cancers did not aggregate within married couples. Established and suspected risk factors, not necessarily related to the marriage, were found for some individuals who had concordance with their spouses. CONCLUSIONS: Little spousal concordance for cancer occurrence was found. The study of spousal aggregation does not appear useful in identifying unsuspected environmental causes of cancer in heterogeneous populations in urban areas of affluent Western countries. A cohort study would have to be much larger than this one to detect weak spousal concordance reliably.

Barbiturates and lung cancer: a re-evaluation.

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.

Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men.

BACKGROUND: The sale of cigars in the United States has been increasing for the past six years. Cigar smoking is a known risk factor for certain cancers and for chronic obstructive pulmonary disease (COPD). However, unlike the relation between cigarette smoking and cardiovascular disease, the association between cigar smoking and cardiovascular disease has not been clearly established. METHODS: We performed a cohort study among 17,774 men 30 to 85 years of age at base line (from 1964 through 1973) who were enrolled in the Kaiser Permanente health plan and who reported that they had never smoked cigarettes and did not currently smoke a pipe. Those who smoked cigars (1546 men) and those who did not (16,228) were followed from 1971 through the end of 1995 for a first hospitalization for or death from a major cardiovascular disease or COPD, and through the end of 1996 for a diagnosis of cancer. RESULTS: In multivariate analysis, cigar smokers, as compared with nonsmokers, were at higher risk for coronary heart disease (relative risk, 1.27; 95 percent confidence interval, 1.12 to 1.45), COPD (relative risk, 1.45; 95 percent confidence interval, 1.10 to 1.91), and cancers of the upper aerodigestive tract (relative risk, 2.02; 95 percent confidence interval, 1.01 to 4.06) and lung (relative risk, 2.14; 95 percent confidence interval, 1.12 to 4.11), with evidence of dose-response effects. There appeared to be a synergistic relation between cigar smoking and alcohol consumption with respect to the risk of oropharyngeal cancers and cancers of the upper aerodigestive tract. CONCLUSIONS: Independently of other risk factors, regular cigar smoking can increase the risk of coronary heart disease, COPD, and cancers of the upper aerodigestive tract and lung.

Cholecystectomy and the risk of colon cancer.

OBJECTIVE: The relationship between cholecystectomy and the occurrence of subsequent colon cancer has been controversial. Using data collected as part of an incident case-control study of colon cancer conducted in northern California, Minnesota, and Utah, we evaluated this association. METHODS: Participants were between 30 and 79 yr of age and had a first primary colon cancer diagnosed between October 1, 1991 and September 30, 1994. Analyses were adjusted for age, gender, family history of colorectal cancer, body mass index, dietary energy and fiber intake, use of aspirin or nonsteroidal antiinflammatory drugs, and long-term leisure-time vigorous physical activity. RESULTS: A weak positive association between cholecystectomy and proximal colon cancer (odds ratio [OR] and 95% confidence interval [CI] 1.3 [1.0-1.6]) was observed. This was counterbalanced by a weak, nonsignificant negative association (OR 0.8, 95% CI 0.6-1.1) with distal colon cancer leading to no overall association (OR 1.0, 95% CI 0.9-1.2). The association between colon cancer and cholecystectomy did not differ by gender or race, but it did differ by study area, with most of the increased association being attributed to the Minnesota population. The elevated risk of proximal colon cancer increased after cholecystectomy but disappeared after 14 years. CONCLUSIONS: Our results suggest that cholecystectomy or the underlying gallstone disease that prompts it may be related weakly to the risk of subsequent proximal colon cancer. However, the association may differ by geographic area of the country, and may be artifactual at least in part.

Barbiturates, smoking, and bladder cancer risk.

Phenobarbital treatment has been observed to be negatively associated with bladder cancer risk in a few studies. It has been suggested that phenobarbital may induce drug-metabolizing enzymes that detoxify the bladder carcinogens found in cigarette smoke. We examined the relationship of barbiturate use to bladder cancer risk and the potential modifying effect of cigarette smoking in a large cohort of Kaiser Permanente Medical Care Program members with computerized pharmacy prescriptions and smoking information. Newly diagnosed bladder cancers were identified among individuals in the study cohort by linkage with data from cancer registries. The overall standardized incidence ratio associated with barbiturate use was 0.71 [95% confidence interval (CI), 0.51-0.99]. Among current smokers, former smokers, and never smokers, the standardized incidence ratios were 0.56 (95% CI, 0.23-1.16), 0.68 (95% CI, 0.27-1.40), and 1.04 (95% CI, 0.48-1.98), respectively. Although our estimates were imprecise, the finding of an inverse association between barbiturate treatment and bladder cancer risk only among current and former cigarette smokers is consistent with the hypothesis that treatment with these medications induces drug-metabolizing enzymes that deactivate bladder carcinogens found in cigarette smoke.

Gastrin and colorectal cancer: a prospective study.

BACKGROUND & AIMS: Gastrin is a putative promoter of colorectal carcinomas. The aim of this study was to evaluate the temporal relationship between gastrinemia and development of colorectal malignancy. METHODS: We conducted a nested case-control study among 128,992 subscribers to a health maintenance program who had participated in a multiphasic health checkup between 1964 and 1969. Serum had been frozen since the checkup and the cohort followed up for cancer. Of 1881 incident colorectal carcinoma cases, 250 were randomly selected; 1 control without cancer was matched to each case by age, sex, education, and date of serum collection. Stored sera were tested for Helicobacter pylori immunoglobulin G and for gastrin and glycine-extended gastrin. RESULTS: Verified cases included 166 colon cancers, 58 rectal cancers, and 9 with cancer in both locations. A mean of 15.3 years had elapsed between serum collection and diagnosis of cancer. Median gastrin levels were similar in cases and controls (41.7 vs. 40.7 pg/mL). However, a gastrin level above normal was associated with increased risk for colorectal malignancy (odds ratio, 3.9; 95% confidence interval, 1.5-9.8). If this association is causal, 8.6% of colorectal cancers could be attributed to high serum gastrin level. CONCLUSIONS: Hypergastrinemia is associated with an increased risk of colorectal carcinoma.