The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

BACKGROUND: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. METHODS: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. DISCUSSION: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.

Incidence of Parkinson disease in North America.

Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease.

BACKGROUND AND PURPOSE: In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. METHODS: Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04). CONCLUSION: In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.

Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study.

The objective of this study was to determine whether patients with multiple sclerosis (MS) are more likely to have other autoimmune disorders particularly prior to the diagnosis of MS. We conducted a population-based case-control study of patients enrolled in the Northern California Kaiser Permanente Medical Care Program. Electronic clinical records through 2005 were used to ascertain incident and prevalent MS cases and identify the presence and timing of 44 other diagnoses. Controls were matched 5:1 for gender, age, and Kaiser membership characteristics. We identified 5296 MS cases (including 924 diagnosed between 2001 and 2004) and 26,478 matched controls. Prior to MS diagnosis, cases were more likely than controls to have uveitis (OR = 3.2, 95%; CI 1.7-5.7), inflammatory bowel disease (IBD, OR = 1.7; 95%CI 1.2-2.5), and Bell's palsy (OR = 3.2; 95%CI 1.2-8.3). Cases were also more likely to develop Guillain- Barré syndrome (GBS, OR = 5.0; 95%CI 1.6-15.4) and bullous pemphigoid (OR = 6.7; 95%CI 1.5-29.9). Cases were not more likely than controls to have or to develop rheumatoid arthritis, lupus or thyroiditis. MS may share environmental triggers, genetic susceptibilities and/or alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders.

Effects of urinary incontinence, comorbidity and race on quality of life outcomes in women.

PURPOSE: We investigated the effects of comorbidity and urinary incontinence on both generic and incontinence specific quality of life outcome measures, and investigated whether the association between urinary incontinence and quality of life varies by race. MATERIALS AND METHODS: Study participants were 2,109 women 40 to 69 years old randomly selected from an urban health maintenance organization and interviewed in person for a study of risk factors for urinary incontinence. The sample was racially diverse consisting of 48% white, 18% black, 17% Hispanic and 16% Asian-American women. In addition to incontinence, reproductive and medical history questionnaires, all participants completed the Medical Outcomes Study Short Form 36, a measure of health related quality of life. All participants with daily and weekly incontinence (29%) completed the Incontinence Impact Questionnaire, an incontinence specific quality of life measure. The health maintenance organization's inpatient and outpatient electronic databases were used to calculate a Charlson comorbidity index score for each participant. ANCOVA was used to produce a model adjusting for sociodemographic variables, comorbidity and incontinence frequency. The same model was run for each of 4 racial groupings to examine differences by race/ethnicity. RESULTS: Urinary incontinence is significantly associated with a decreased quality of life and those with more frequent incontinence have significantly lower quality of life scores. In our model the Charlson score, an objective measure of comorbidity based on hospital and physician records, also has a significant negative impact on quality of life. When comorbidity is controlled, incontinence frequency continues to have a significant negative association with quality of life except among the sickest women. For women with the greatest extent of comorbidity, incontinence frequency is not significantly associated with negative quality of life outcomes. We did not find clear patterns of variation by race. CONCLUSIONS: Urinary incontinence and comorbidity each have an independent and significant role in reducing quality of life outcomes for all but the sickest women.

Prevalence of Parkinson's disease across North America.

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

Urinary incontinence and pelvic floor dysfunction in Asian-American women.

OBJECTIVE: The objective of the study was to describe the prevalence, risk factors, and impact of urinary incontinence and other pelvic floor disorders among Asian-American women. STUDY DESIGN: This was a population-based cohort study of older women randomly selected from age and race strata. RESULTS: Weekly urinary incontinence was reported by 65 of 345 Asian women (18%), with stress and urge incontinence being approximately equally common. In multivariate analysis, higher body mass index (greater than 25 kg/m2) was associated with both stress incontinence (odds ratio 4.90, 95% confidence interval 1.76 to 13.68) and urge incontinence (odds ratio 2.49, 95% confidence interval 1.01 to 6.16) in Asians. Hysterectomy was a significant risk factor for stress incontinence (odds ratio 2.79, 95% confidence interval 1.03 to 7.54). Only 34% of Asian women with weekly urinary incontinence reported ever having sought treatment. Pelvic floor exercises were the most common form of treatment, being used by 29% of Asian women with weekly incontinence. Asians were less likely then white women to report anal incontinence (21% versus 29%, P = .007), although this difference became nonsignificant after adjusting for differences in risk factors. CONCLUSION: Asian women share some risk factors for stress and urge urinary incontinence with white women. Urinary incontinence is associated with anal incontinence among Asian women.

Race, prostate cancer survival, and membership in a large health maintenance organization.

BACKGROUND: Population-based cancer registry data have shown that black men with prostate cancer have poorer stage-specific survival than white men, while studies in equal-access health care systems have not found racial differences in stage-specific survival. This study was designed to test the hypothesis that black men and white men with prostate cancer have equal stage-specific survival in equal-access health care systems. METHODS: We conducted a cohort study using cancer registry data from all incident cases of prostate cancer occurring in a five-county San Francisco Bay Area region. Incident cases occurred among members (5263 cases, from January 1973 through June 1995) and nonmembers (16,019 cases, from January 1973 through December 1992) of the Kaiser Permanente Medical Care Program, a large health maintenance organization. Death rate ratios (DRRs, black men versus white men) for Kaiser members and nonmembers were computed for all stages combined (adjusting for age and stage) and for each stage (adjusting for age). RESULTS: Among Kaiser members, adjusted DRRs comparing black men with white men were as follows: all stages combined, 1.28 (95% confidence interval [CI] = 1.14-1.44); local stage, 1.23 (95% CI = 1.01-1.51); regional stage, 1.30 (95% CI = 0.97-1.75); and distant stage, 1.27 (95% CI = 1.07-1.50). Corresponding DRRs for nonmembers were as follows: all stages combined, 1.22 (95% CI = 1.14-1.30); local stage, 1.24 (95% CI = 1.09-1.41); regional stage, 1.48 (95% CI = 1.29-1.68); and distant stage, 1.01 (95% CI = 0.91-1.12). CONCLUSIONS: These results show poorer prostate cancer survival for black men compared with white men in an equal-access medical care setting. The findings are most consistent with the hypothesis of increased tumor virulence in blacks.

Aspartame ingestion and headaches: a randomized crossover trial.

To examine whether ingestion of aspartame is associated with headaches, we conducted a double-blind crossover study using volunteers with self-identified headaches after using aspartame. Of the 32 subjects randomized to receive aspartame (approximately 30 mg/kg/d) and placebo in a two-treatment, four-period crossover design, 18 completed the full protocol, seven completed part of the protocol before withdrawing due to adverse effects, three withdrew for other reasons, two were lost to follow-up, one was withdrawn due to noncompliance, and one withdrew and gave no reason. Each experimental period was 7 days long. Subjects reported headaches on 33% of the days during aspartame treatment, compared with 24% on placebo treatment (p = 0.04). Subjects who were "very sure" prior to the study that aspartame triggered some of their headaches reported larger treatment differences (aspartame = 0.37 headache-days, placebo = 0.18 headache-days; p < 0.001) than subjects who were "somewhat sure" (aspartame = 0.29 headache-days, placebo = 0.22 headache-days; p = 0.51) or "not sure" (aspartame = 0.33 headache-days, placebo = 0.39 headache-days; p = 0.51). There was no significant treatment difference in the length or intensity of headaches or in the occurrence of side effects associated with the headaches. This experiment provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.

Risk factors for pancreatic cancer: an exploratory study.

An exploratory case-control study to detect risk factors for pancreatic cancer was conducted within a large cohort of people who had received multiphasic health checkups in the San Francisco Bay Area. Four hundred and fifty who later developed pancreatic cancer were compared with 2687 who did not with respect to 779 characteristics recorded at the checkups. There was strong confirmation that cigarette smoking and diabetes mellitus were associated with risk of subsequent pancreatic cancer. Higher levels of serum iron, iron saturation and body weight were also predictive. Less striking associations of interest were with the leukocyte count, pulse rate and certain questionnaire items suggesting non-specific health impairment. Past concerns about alcohol and coffee consumption were not confirmed.

Evaluation of parturition and other reproductive variables as risk factors for urinary incontinence in later life.

OBJECTIVE: To assess specific parturition and reproductive variables as potential risk factors for urinary incontinence in later life. METHODS: A mail survey was conducted with a random sample of 1922 women members of a large health maintenance organization. Multivariate analysis was used to estimate the independent association between parturition factors, hysterectomy, hormone use, and incontinence. RESULTS: Completed surveys were returned by 939 women (49%), 682 of whom reported at least one episode of incontinence in the past 12 months or ever having been treated for incontinence. On univariate analysis, women with incontinence were more likely to be white and heavier and to have had a hysterectomy before age 45, at least one live birth, a postdate (at least 42 weeks' gestation) birth, a labor lasting longer than 24 hours, and exposure to oxytocin. The risk of incontinence increased significantly with the number of exposures to oxytocin. In a multivariate model including age, there was a significant association between incontinence and white race (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.2, 2.8), body mass (OR for fourth quartile 3.0, 95% CI 1.8, 5.0), estrogen replacement (OR 1.9, 95% CI 1.3, 2.8) and oxytocin (OR 1.9, 95% CI 1.0, 3.6). Parity was also associated with incontinence (P < .05). CONCLUSION: This study supports previous findings of a positive association between urinary incontinence and body mass, parity, and use of estrogen. In addition, we found a significant independent association between exposure to oxytocin during labor and incontinence in later life.

The cost of health conditions in a health maintenance organization.

In this retrospective cohort analysis of all adults who were members of Kaiser Permanente, Northern California, between July 1995 and June 1996 (N = 2,076,303), the authors estimated the prevalence, average annual costs per person, and percentage of total direct medical expenditures attributable to each of 25 chronic and acute conditions. Ordinary least squares regression was used to adjust for age, gender, and comorbidities. The costs attributable to the 25 conditions accounted for 78 percent of the health maintenance organization's total direct medical expense for this age-group. Injury accounted for a higher proportion (11.5 percent) of expenditures than any other single condition. Three cardiovascular conditions--ischemic heart disease, hypertension, and congestive heart failure--together accounted for 17 percent of direct medical expense and separately accounted for 6.8 percent, 5.7 percent, and 4.0 percent, respectively. Renal failure ($22,636), colorectal cancer ($10,506), pneumonia ($9,499), and lung cancer ($8,612) were the most expensive conditions per person per year.

Race/ethnicity, social class, and prevalence of breast cancer prognostic biomarkers: a study of white, black, and Asian women in the San Francisco bay area.

We assessed distributions of breast cancer prognostic biomarkers by race/ethnicity and socioeconomic position among paraffin-embedded tumor biopsy specimens from 135 US women (48 white women, 44 black women, 43 Asian women) diagnosed with breast cancer between 1966 and 1990. No racial/ethnic or socioeconomic differences in distributions were observed for tumor stage, lymph node involvement, estrogen, progesterone, and epidermal growth factor receptors, oncogenes such as Her2/neu and p53, cytoplasmic proteins cathepsin-D and ps2, and two indices of cell growth, Ki67 and DNA ploidy, adjusting for age at diagnosis, menopausal status, place of birth and, for racial/ethnic comparisons, working class composition of census block-group at diagnosis. Black and Asian women, however, were 3.5 times (95% confidence interval [CI] = 1.2, 10.1) and 3.7 times (95% CI = 1.3, 10.6), respectively more likely than white women to have a tumor size of > or = 20 mm, and Asian women were 3.4 times (95% CI = 1.1, 10.4) more likely than black women to be positive for androgen receptor, adjusting for these same factors. No differences in distributions by socioeconomic position were observed for these latter two tumor characteristics. These data suggest that racial/ethnic and socioeconomic disparities in breast cancer survival are unlikely to be explained solely by differential distributions of molecular breast cancer prognostic biomarkers.

Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium.

OBJECTIVE: To examine genetic associations of polymorphisms in the dopamine receptor D2 (DRD2) and D3 (DRD3) genes with risk of Parkinson's disease (PD). METHODS: The study included 1325 newly diagnosed patients with PD and 1735 controls from a consortium of five North American case-control studies. We collected risk factor information by in-person or telephone interview. Six DRD2 and two DRD3 polymorphisms were genotyped using a common laboratory. Odds ratios were estimated using logistic regression. RESULTS: Among non-Hispanic whites, homozygous carriers of Taq1A DRD2 (rs1800497) polymorphism had an increased risk of PD compared to homozygous wildtype carriers (OR=1.5, 95% CI 1.0-2.3). In contrast, the direction of association for Taq1A polymorphism was opposite for African-Americans, showing an inverse association with PD risk (OR=0.10, 95% CI 0.2-0.7). Among white Hispanics who carried two alleles, the Ser9Gly DRD3 (rs6280) polymorphism was associated with a decreased risk of PD (OR=0.4, 95% CI 0.2-0.8). The inverse association of smoking with PD risk was not modified by any of the DRD2 or DRD3 polymorphisms. CONCLUSIONS: DRD2 polymorphisms are unlikely to be true disease-causing variants; however, three DRD2 polymorphisms (including Taq1A) may be in linkage disequilibrium with possible disease associated variants in the DRD2-ANKK1-NCAM1-TTC12 gene cluster.

Pelvic floor disorders and quality of life in women with self-reported irritable bowel syndrome.

BACKGROUND: Quality of life among women with irritable bowel syndrome may be affected by pelvic floor disorders. AIM: To assess the association of self-reported irritable bowel syndrome with urinary incontinence, pelvic organ prolapse, sexual function and quality of life. METHODS: We analysed data from the Reproductive Risks for Incontinence Study at Kaiser Permanente, a random population-based study of 2109 racially diverse women (mean age = 56). Multivariate analyses assessed the association of irritable bowel syndrome with pelvic floor disorders and quality of life. RESULTS: The prevalence of irritable bowel syndrome was 9.7% (n = 204). Women with irritable bowel had higher adjusted odds of reporting symptomatic pelvic organ prolapse (OR 2.4; 95% CI, 1.4-4.1) and urinary urgency (OR 1.4; 95% CI, 1.0-1.9); greater bother from pelvic organ prolapse (OR 4.3; 95% CI, 1.5-11.9) and faecal incontinence (OR 2.0; 95% CI, 1.3-3.2); greater lifestyle impact from urinary incontinence (OR 2.2; 95% CI, 1.3-3.8); and worse quality of life (P < 0.01). Women with irritable bowel reported more inability to relax and enjoy sexual activity (OR 1.8; 95% CI, 1.3-2.6) and lower ratings for sexual satisfaction (OR 1.8; 95% CI, 1.3-2.5), but no difference in sexual frequency, interest or ability to have an orgasm. CONCLUSIONS: Women with irritable bowel are more likely to report symptomatic pelvic organ prolapse and sexual dysfunction, and report lower quality of life.

Minimum incidence of primary cervical dystonia in a multiethnic health care population.

BACKGROUND: The two existing estimates of the incidence of primary cervical dystonia were based on observations in relatively ethnically homogeneous populations of European descent. OBJECTIVE: To estimate the minimum incidence of primary cervical dystonia in the multiethnic membership of a health maintenance organization in Northern California. METHODS: Using a combination of electronic medical records followed by medical chart reviews, we identified incident cases of cervical dystonia first diagnosed between 1997 and 1999. RESULTS: We identified 66 incident cases of cervical dystonia from 8.2 million person-years of observation. The minimum estimate of the incidence of cervical dystonia in this population is 0.80 per 100,000 person-years. Ethnicity-specific incidence rates were calculated for individuals over age 30. Incidence was higher in white individuals (1.23 per 100,000 person-years) than in persons of other races (0.15 per 100,000 person-years, p < 0.0001). The minimum estimated incidence was 2.5 times higher in women than in men (1.14 vs 0.45 per 100,000 person-years, p = 0.0005). The average age at diagnosis was higher in women (56 years) than in men (45 years, p = 0.0004). There was no significant difference in reported symptom duration prior to diagnosis between women and men (3.9 vs 5.3 years). CONCLUSION: The estimated incidence of diagnosed cervical dystonia among white individuals in this Northern Californian population is similar to previous estimates in more ethnically homogeneous populations of largely European descent. The incidence in other races, including Hispanic, Asian, and black appears to be significantly lower. The incidence is also higher in women than in men.

Effect of reproductive factors and postmenopausal hormone use on the risk of Parkinson disease.

OBJECTIVE: Parkinson disease (PD) is less common in women possibly because of hormonal or reproductive influences. The objective of this study was to evaluate the associations of reproductive factors and postmenopausal hormone use with the risk of PD among postmenopausal women. METHODS: Incident cases (n = 178) and randomly selected age-matched controls (n = 189) who were members of the Kaiser Permanente Medical Care Program (KPMCP) of Northern California participated in the study conducted during the years 1994 to 1995. Statistical analyses were carried out using logistic regression. RESULTS: The association of postmenopausal hormone use with PD risk depended on the type of menopause. Among women with history of a hysterectomy with or without an oophorectomy, estrogen use alone was associated with a 2.6-fold increased risk (adjusted odds ratio (OR) 2.6, 95% CI: 1.1 to 6.1) and significant trends in the risk of PD were observed with increasing duration of estrogen use, but disease risk was not influenced by recency of use. In contrast, among women with natural menopause, no increased risk of PD was observed with hormone use (estrogen alone or a combined estrogen-progestin regimen). Early age at final menstrual period (44 years or younger) was associated with reduction in risk (adjusted OR 0.5, 95% CI: 0.3 to 1.0). Age at menarche and parity were not associated with the risk of PD. CONCLUSION: Postmenopausal use of estrogen alone may increase the risk of Parkinson disease (PD) among women with a hysterectomy. Among women with natural menopause for whom the usual treatment is combined estrogen-progestin therapy, no increased risk of PD was observed.

A conditional analysis for two-treatment multiple-period crossover designs with binomial or poisson outcomes and subjects who drop out.

We propose a conditional analysis for outcome data on numbers of recurrent symptoms arising in a two-treatment, multiple-period crossover trial. Conditioning on subject-specific totals removes any dependence on mean subject-specific symptom rates and permits the use of standard software to perform regression analysis to examine treatment, period, carryover and interaction effects. The addition of offsets to the regression equations allows the incorporation of data from subjects who do not complete all periods in the trial. We apply the proposed method to data from a crossover trial and discuss its advantages and disadvantages.

Forced expiratory volume (1 second) and lung cancer incidence and mortality.

We evaluated the relation between forced expiratory volume in 1 second (FEV1) and lung cancer incidence and mortality among members of the Kaiser Permanente Medical Care Program who took a multiphasic health checkup. FEV1 was inversely related to risk of lung cancer among former and current smokers, but not related among never-smokers. We observed a decreased risk of lung cancer mortality only in the higher quintiles of FEV1 in current smokers among men, but not in women. FEV1 appears to be associated with lung cancer as a physiologic marker for smoking-induced pulmonary damage.

Exposure to engine exhaust and risk of subsequent cancer.

We evaluated the relation between occupational exposure to engine exhaust fumes and cancer risk among members of a large prepaid health plan who reported on exposure during a routine health examination (n = 160,230). Exposure in the past year was associated with an elevated risk of cancer of the thyroid (relative risk (RR) = 1.99; 95% confidence interval (CI), 1.01-3.92), female breast (RR = 1.53; CI, 1.00-2.33), nonbrain nervous system (RR = 2.26; CI, 1.09-4.67), and lip/tongue (RR = 1.82; CI, 1.09-3.04), and a decreased risk of melanoma (RR = 0.50; CI, 0.27-0.90). However, another measure of exposure that included both exposure prior to 1 year and exposure in the past year was associated only with cancer of the lip/tongue (RR = 1.82; CI, 1.02-3.32). No association was observed for lung, bladder, or larynx cancer or multiple myeloma. Analyses limited to men, or stratified by time since health examination, did not distinguish other effects. Self-reported occupational exposure to engine exhaust fumes was not convincingly associated with most cancers in this cohort.