Rationale, Procedures, and Response Rates for a Pilot Study to Sample Cancer Survivors for NCI's Health Information National Trends Survey: HINTS-SEER 2021.

The National Cancer Institute's (NCI) Health Information National Trends Survey (HINTS) is a nationally representative survey of U.S. adults in which 12-17% of respondents report a cancer history. To increase representation from adult cancer survivors, in 2021, NCI sampled survivors from three Surveillance, Epidemiology, and End Results (SEER) program cancer registries: Iowa, New Mexico, and the Greater Bay Area. Sampling frames were stratified by time since diagnosis and race/ethnicity, with nonmalignant tumors and non-melanoma skin cancers excluded. Participants completed a self-administered postal questionnaire. The overall response rate for HINTS-SEER (N = 1,234) was 12.6%; a non-response bias analysis indicated few demographic differences between respondents and the pool of sampled patients in each registry. Most of the sample was 10+ years since diagnosis (n = 722; 60.2%); 392 respondents were 5 to < 10 years since diagnosis (29.6%); and 120 were < 5 years since diagnosis (10.2%). Common cancers included male reproductive (n = 304; 24.6%), female breast (n = 284; 23.0%), melanoma (n = 119; 9.6%), and gastrointestinal (n = 106; 8.6%). Tumors were mostly localized (67.8%; n = 833), with 22.4% (n = 282) regional, 6.2% (n = 72) distant, and 3.7% (n = 47) unknown. HINTS-SEER data are available by request and may be used for secondary analyses to examine a range of social, behavioral, and healthcare outcomes among cancer survivors.

Epidemiology of Gastric Malignancies 2000-2018 According to Histology: A Population-Based Analysis of Incidence and Temporal Trends.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S. POPULATIONS: However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear. METHODS: We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons. RESULTS: Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%), GIST (6.7%), NET (6.4%), and MALT lymphoma (5.6%). Noncardia GA ASIR was significantly higher than other histologies and demonstrated the greatest differences by race and ethnicity. APCs for GA and MALT, both Helicobacter pylori-associated cancers, declined significantly over time, which was driven primarily by trends among individuals ≥50 years-old. NET and GIST APCs significantly increased irrespective of age group, with the highest APCs observed among non-Hispanic white individuals. Cardia GC was rarer than noncardia GC and comprised primarily by GA (87.9%). Cardia GC incidence fell during the study period, which was primarily driven by decline in cardia GA. CONCLUSIONS: GA was the most common histology. On the basis of our findings, the rise in noncardia GC among certain U.S. populations appears predominantly driven by NET and GIST, not GA. Further studies are needed to clarify underlying etiologies for these findings.

Characterizing breast cancer incidence and trends among Asian American, Native Hawaiian, and non-Hispanic White women in Hawai'i, 1990-2014.

PURPOSE: To characterize breast cancer (BC) incidence by age at diagnosis and BC subtype among disaggregated Asian American, Native Hawaiian, and Pacific Islander (AANHPI) women and non-Hispanic White (NHW) women in Hawai'i. METHODS: Using 1990-2014 data from the Hawai'i tumor registry, we estimated age-adjusted incidence rates (AAIR) of BC and the annual percent change in BC incidence by age (<50 and ≥50 years) and BC subtype (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-, HR+/HER2+, HR-/HER2+, triple negative BC) for Filipino American (FA), Japanese American (JA), Native Hawaiian (NH), and NHW women. RESULTS: Among young (<50 years) women, annual BC incidence increased 2.9% (1994-2014) among JA and 1.0% (1990-2014) among NHW women. Incidence was highest among young JA women (2010-2014 AAIR 52.0 per 100,000; 95% confidence interval [CI] 45.6, 58.9). HR+/HER2- BC, the major BC subtype, was similarly highest among young JA women (AAIR 39.5; 95% CI 33.9, 45.4). Among older (≥50 years) women, annual BC incidence increased 1.6% (1990-2014) among FA and 4.2% (2006-2014) for JA women. BC incidence was highest among older NH women (AAIR 137.6, 95% CI 128.2, 147.4), who also displayed highest incidence of two subtypes: HR+/HER2- (AAIR 106.9; 95% CI 98.6, 115.5) and HR+/HER2+ (AAIR 12.1; 95% CI 9.4, 15.1). CONCLUSION: We observed high and increasing BC incidence among JA women ages <50 years and high incidence among NH women ages ≥50 years. These results highlight racial and ethnic differences in BC incidence among disaggregated AANHPI populations in Hawai'i by age and BC subtype.

Population-Based Analysis of Differences in Gastric Cancer Incidence Among Races and Ethnicities in Individuals Age 50 Years and Older.

BACKGROUND & AIMS: There are racial and ethnic differences in the incidence of gastric adenocarcinoma worldwide and in the US. Based on a decision analysis, screening for noncardia gastric adenocarcinoma might be cost-effective for non-White individuals 50 years or older. However, a lack of precise, contemporary information on gastric adenocarcinoma incidence in specific anatomic sites for this age group has impeded prevention and early detection programs in the US. We aimed to estimate the differences in gastric adenocarcinoma incidence in specific anatomic sites among races and ethnicities in individuals 50 years or older. METHODS: We analyzed California Cancer Registry data from 2011 through 2015 to estimate incidences of gastric adenocarcinoma in specific anatomic sites for non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 7 largest Asian American populations. We calculated the differential incidence between non-White groups and NHW using incidence rate ratios and 95% confidence intervals (CIs). RESULTS: Compared with NHW subjects, all non-White groups had significantly higher incidences of noncardia gastric adenocarcinoma; the incidence was highest among Korean American men 50 years and older (70 cases per 100,000). Compared with NHW subjects 50 years and older, the risk of noncardia gastric adenocarcinoma was 1.8-fold (95% CI, 1.37-2.31) to 7.3-fold (95% CI, 5.73-9.19) higher in most non-White groups and 12.0-fold (95% CI, 9.96-14.6) to 14.5-fold (95% CI, 12.5-16.9) higher among Korean American men and women 50 years and older, respectively. Compared with NHW men 50 years and older, all non-White men, except Japanese and Korean American men, had a significantly lower risk of cardia gastric adenocarcinoma. CONCLUSIONS: We identified several-fold differences in incidences of gastric adenocarcinoma in specific anatomic sites among racial and ethnic groups, with significant age and sex differences. These findings can be used to develop targeted risk reduction programs for gastric adenocarcinoma.

Testicular cancer in Hispanics: incidence of subtypes over time according to neighborhood sociodemographic factors in California.

PURPOSE: Hispanic men in the USA experience the second-highest incidence rate of testicular germ cell tumors (TGCTs), behind non-Hispanic (NH) White men, and have experienced steep increases in TGCT in recent decades. It is unknown whether increases in incidence differ according to neighborhood sociodemographic factors. METHODS: We conducted a population-based study of n = 3759 Hispanic and n = 8469 NH White men (n = 12,228 total) diagnosed with TGCT in California during the three most recent pericensal periods. We calculated incidence rates according to neighborhood socioeconomic status (nSES) and among Hispanics, according to ethnic enclave. We calculated incidence rate ratios to compare rates across nSES and ethnic enclave and to examine changes in rates over pericensal time periods according to these neighborhood factors for major histologic types (i.e., seminoma and nonseminoma). RESULTS: Hispanic men residing in high SES, compared to low SES, neighborhoods had greater incidence of seminoma and nonseminoma testicular cancer across pericensal periods, as did Hispanic men in low enclave (less ethnic), compared to high enclave, neighborhoods. Between the periods 1998-2002 and 2008-2012, Hispanic men residing in low SES neighborhoods experienced a 39% increased incidence of seminoma, while those residing in low and middle SES neighborhoods experienced 87% and 48% increased incidence of nonseminoma, respectively. CONCLUSION: While TGCT incidence has increased among all Hispanic men, incidence increases appear to be driven disproportionately by those residing in lower SES and lower enclave neighborhoods, particularly for nonseminoma.

Breast cancer in Asian Americans in California, 1988-2013: increasing incidence trends and recent data on breast cancer subtypes.

PURPOSE: In contrast to other US racial/ethnic groups, Asian Americans (AA) have experienced steadily increasing breast cancer rates in recent decades. To better understand potential contributors to this increase, we examined incidence trends by age and stage among women from seven AA ethnic groups in California from 1988 to 2013, and incidence patterns by subtype and age at diagnosis for the years 2009 through 2013. METHODS: Joinpoint regression was applied to California Cancer Registry data to calculate annual percentage change (APC) for incidence trends. Incidence rate ratios were used to compare rates for AA ethnic groups relative to non-Hispanic whites (NHW). RESULTS: All AA groups except Japanese experienced incidence increases, with the largest among Koreans in 1988-2006 (APC 4.7, 95% CI 3.8, 5.7) and Southeast Asians in 1988-2013 (APC 2.5, 95% CI 0.8, 4.2). Among women younger than age 50, large increases occurred for Vietnamese and other Southeast Asians; among women over age 50, increasing trends occurred in all AA ethnic groups. Rates increased for distant-stage disease among Filipinas (2.2% per year, 95% CI 0.4, 3.9). Compared to NHW, Filipinas and older Vietnamese had higher incidence rates of some HER2+ subtypes. CONCLUSIONS: Breast cancer incidence rates have risen rapidly among California AA, with the greatest increases in Koreans and Southeast Asians. Culturally tailored efforts to increase awareness of and attention to breast cancer risk factors are needed. Given the relatively higher rates of HER2-overexpressing subtypes in some AA ethnicities, research including these groups and their potentially unique exposures may help elucidate disease etiology.

Residential cancer cluster investigation nearby a Superfund Study Area with trichloroethylene contamination.

PURPOSE: Trichloroethylene (TCE) is an industrial solvent associated with liver cancer, kidney cancer, and non-Hodgkin's lymphoma (NHL). It is unclear whether an excess of TCE-associated cancers have occurred surrounding the Middlefield-Ellis-Whisman Superfund site in Mountain View, California. We conducted a population-based cancer cluster investigation comparing the incidence of NHL, liver, and kidney cancers in the neighborhood of interest to the incidence among residents in the surrounding four-county region. METHODS: Case counts and address information were obtained using routinely collected data from the Greater Bay Area Cancer Registry, part of the Surveillance, Epidemiology, and End Results program. Population denominators were obtained from the 1990, 2000, and 2010 US censuses. Standardized incidence ratios (SIRs) with two-sided 99 % confidence intervals (CIs) were calculated for time intervals surrounding the US Censuses. RESULTS: There were no statistically significant differences between the neighborhood of interest and the larger region for cancers of the liver or kidney. A statistically significant elevation was observed for NHL during one of the three time periods evaluated (1996-2005: SIR = 1.8, 99 % CI 1.1-2.8). No statistically significant NHL elevation existed in the earlier 1988-1995 (SIR = 1.3, 99 % CI 0.5-2.6) or later 2006-2011 (SIR = 1.3, 99 % CI 0.6-2.4) periods. CONCLUSION: There is no evidence of an increased incidence of liver or kidney cancer, and there is a lack of evidence of a consistent, sustained, or more recent elevation in NHL occurrence in this neighborhood. This evaluation included existing cancer registry data, which cannot speak to specific exposures incurred by past or current residents of this neighborhood.

The effect of clothing care activities on textile formaldehyde content.

Textiles are commonly treated with formaldehyde-based residues that may potentially induce allergic contact dermatitis in sensitive individuals. This study examined the initial formaldehyde content in clothing and resulting changes due to care activities. Twenty clothing articles were examined and 17 of them did not have detectable levels of formaldehyde. One shirt contained a formaldehyde concentration of 3172 ppm, and two pairs of pants had formaldehyde concentrations of 1391 ppm and 86 ppm. The two highest results represent formaldehyde levels that are up to 40-fold greater than international textile regulations. The two items with the greatest formaldehyde content were washed and dried in a manner similar to that used by consumers, including hand and machine washing in hot or cold water followed by air or machine drying. The washing and drying procedures reduced formaldehyde levels to between 26 and 72% of untreated controls. Differences in the temperature or type of washing and drying did not result in a clear trend in the subsequent formaldehyde content. In addition, samples were hot ironed, which did not affect the formaldehyde content as significantly. Understanding the formaldehyde content in clothing and its potential reduction through care activities may be useful for manufacturers and formaldehyde-sensitive individuals.

Evaluation of take home (para-occupational) exposure to asbestos and disease: a review of the literature.

The potential for para-occupational (or "take-home") exposure to a number of chemicals has been recognized for over 60 years. We conducted a literature review in order to characterize reported cases of asbestos-related disease among household contacts of workers occupationally exposed to asbestos. Over 200 published articles were evaluated. Nearly 60 articles described cases of asbestos-related disease thought to be caused by para-occupational exposure. Over 65% of these cases were in persons who lived with workers classified as miners, shipyard workers, insulators, or others involved in the manufacturing of asbestos-containing products, with nearly all remaining workers identified as craftsmen. 98% of the available lung samples of the persons with diseases indicated the presence of amphibole asbestos. Eight studies provided airborne asbestos concentrations during (i) handling of clothing contaminated with asbestos during insulation work or simulated use of friction products; (ii) ambient conditions in the homes of asbestos miners; and (iii) wearing previously contaminated clothing. This review indicates that the literature is dominated by case reports, the majority of which involved household contacts of workers in industries characterized, generally, by high exposures to amphiboles or mixed mineral types. The available data do not implicate chrysotile as a significant cause of disease for household contacts. Also, our analysis indicates that there is insufficient information in the published literature that would allow one to relate airborne asbestos concentrations in a workplace to those that would be generated from subsequent handling of contact with clothing that had been contaminated in that environment. Ideally, a simulation study could be conducted in the future to better understand the relationships between the airborne concentrations in the workplace and the fiber characteristics that influence retention on fabric, as well as the concentrations that can be generated by handling the contaminated clothing by the persons in the home.

State-of-the-science review of the occupational health hazards of crystalline silica in abrasive blasting operations and related requirements for respiratory protection.

Excessive exposures to airborne crystalline silica have been known for over 100 years to pose a serious health hazard. Work practices and regulatory standards advanced as the knowledge of the hazards of crystalline silica evolved. This article presents a comprehensive historical examination of the literature on exposure, health effects, and personal protective equipment related to silica and abrasive blasting operations over the last century. In the early 1900s, increased death rates and prevalence of pulmonary disease were observed in industries that involved dusty operations. Studies of these occupational cohorts served as the basis for the first occupational exposure limits in the 1930s. Early exposure studies in foundries revealed that abrasive blasting operations were particularly hazardous and provided the basis for many of the engineering control and respiratory protection requirements that are still in place today. Studies involving abrasive blasters over the years revealed that engineering controls were often not completely effective at reducing airborne silica concentrations to a safe level; consequently, respiratory protection has always been an important component of protecting workers. During the last 15-20 yr, quantitative exposure-response modeling, experimental animal studies, and in vitro methods were used to better understand the relationship between exposure to silica and disease in the workplace. In light of Occupational Safety and Health Administration efforts to reexamine the protectiveness of the current permissible exposure limit (PEL) for crystalline silica and its focus on protecting workers who are known to still be exposed to silica in the workplace (including abrasive blasters), this state-of-the-science review of one of the most hazardous operations involving crystalline silica should provide useful background to employers, researchers, and regulators interested in the historical evolution of the recognized occupational health hazards of crystalline silica and abrasive blasting operations and the related requirements for respiratory protection.

Worker exposure to methanol vapors during cleaning of semiconductor wafers in a manufacturing setting.

An exposure simulation was conducted to characterize methanol exposure of workers who cleaned wafers in quality control departments within the semiconductor industry. Short-term (15 min) and long-term (2-4 hr) personal and area samples (at distances of 1 m and 3-6 m from the source) were collected during the 2-day simulation. On the first day, 45 mL of methanol were used per hour by a single worker washing wafers in a 102 m(3) room with a ventilation rate of about 10 air changes per hour (ACH). Virtually all methanol volatilized. To assess exposures under conditions associated with higher productivity, on the second day, two workers cleaned wafers simultaneously, together using methanol at over twice the rate of the first day (95 mL/hr). On this day, the ventilation rate was halved (5 ACH). Personal concentrations on the first day averaged 60 ppm (SD = 46 ppm) and ranged from 10-140 ppm. On the second day, personal concentrations for both workers averaged 118 ppm (SD = 50 ppm; range: 64-270 ppm). Area concentrations measured on the first day at 1 m from the source and throughout the balance of the room averaged 29 ppm (SD = 19 ppm; range: 4-83 ppm) and 18 ppm (SD = 12 ppm; range: 3-42 ppm), respectively. As expected, area concentrations measured on the second day were higher than the first and averaged 73 ppm (SD = 25 ppm; range: 27-140 ppm) at 1 meter and 48 ppm (SD = 13 ppm; range: 21-67 ppm) throughout the balance of the room. The results of this simulation suggest that the use of methanol to clean semiconductor wafers without the use of local exhaust ventilation and with relatively low room ventilation rates is unlikely to result in worker exposures exceeding the current ACGIH(R) threshold limit value of 200 ppm. This study also confirmed prior studies suggesting that when a relatively volatile chemical is located within arm's length (near field), breathing zone concentrations will be about two- to threefold greater than the room concentration when the air exchange rate is 5-10 ACH.

Colorectal Cancer Incidence Trends by Age, Stage, and Racial/Ethnic Group in California, 1990-2014.

Background: The incidence of colorectal cancer in the United States declined substantially over the past 20 years, but evidence suggests that among younger adults (under 50 years at diagnosis), incidence is increasing. However, data on age- and stage-specific incidence trends across racial/ethnic groups are limited.Methods: All incident cases of colorectal cancer diagnosed from 1990 through 2014 in adults aged 20 years and older were obtained from the California Cancer Registry. Incidence rates (per 100,000), incidence rate ratios, and triannual percent changes in incidence were estimated for each age group at diagnosis (20-49, 50-74, 75+ years), sex, stage, and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and 7 Asian American groups).Results: Of 349,176 incident colorectal cancer cases diagnosed from 1990 through 2014, 9% were in adults younger than 50 years. Increases in incidence of early-onset colorectal cancer, especially in regional/distant stage disease, were observed in most racial/ethnic groups (statistically significant for non-Hispanic whites and Hispanics, ranging from 0.9% to 2.9% every 3 years). Incidence also increased in Vietnamese and other Southeast Asian groups of screening age (50-74 years). The incidence of colorectal cancer in non-Hispanic blacks aged 50+ declined over the 25-year period, but remained significantly higher than in non-Hispanic whites.Conclusions: Further research is needed to understand the causes of the increasing incidence of early-onset colorectal cancer. The rising incidence of colorectal cancer among Southeast Asians of screening age and the persistently high incidence in non-Hispanic blacks also warrant attention.Impact: Our findings may have implications for revisiting screening guidelines in the United States. Cancer Epidemiol Biomarkers Prev; 27(9); 1011-8. ©2018 AACR.

Incidence of lung cancer histologic cell-types according to neighborhood factors: A population based study in California.

BACKGROUND: The relationships between neighborhood factors (i.e., neighborhood socioeconomic status (nSES) and ethnic enclave) and histologic subtypes of lung cancer for racial/ethnic groups, particularly Hispanics and Asian American/Pacific Islanders (AAPIs), are poorly understood. METHODS: We conducted a population-based study of 75,631 Californians diagnosed with lung cancer from 2008 through2012. We report incidence rate ratios (IRRs) for lung cancer histologic cell-types by nSES among racial/ethnic groups (non-Hispanic (NH) Whites, NH Blacks, Hispanics and AAPIs) and according to Hispanic or Asian neighborhood ethnic enclave status among Hispanics and AAPIs, respectively. In addition, we examined incidence jointly by nSES and ethnic enclave. RESULTS: Patterns of lung cancer incidence by nSES and ethnic enclave differed across race/ethnicity, sex, and histologic cell-type. For adenocarcinoma, Hispanic males and females, residing in both low nSES and high nSES neighborhoods that were low enclave, had higher incidence rates compared to those residing in low nSES, high enclave neighborhoods; males (IRR, 1.17 [95% CI, 1.04-1.32] and IRR, 1.15 [95% CI, 1.02-1.29], respectively) and females (IRR, 1.29 [95% CI, 1.15-1.44] and IRR, 1.51 [95% CI, 1.36-1.67], respectively). However, AAPI males residing in both low and high SES neighborhoods that were also low enclave had lower adenocarcinoma incidence. CONCLUSIONS: Neighborhood factors differentially influence the incidence of lung cancer histologic cell-types with heterogeneity in these associations by race/ethnicity and sex. For Hispanic males and females and AAPI males, neighborhood ethnic enclave status is strongly associated with lung adenocarcinoma incidence.

Lung cancer incidence trends in California by race/ethnicity, histology, sex, and neighborhood socioeconomic status: An analysis spanning 28 years.

OBJECTIVES: Lung cancer incidence trends by histology, sex, race/ethnicity, and neighborhood socioeconomic status (nSES) have not been previously reported. We conducted a population-based study of lung cancer incidence over three peri-censal periods: 1988-1992, 1998-2002, and 2008-2012. MATERIALS AND METHODS: We abstracted lung cancer cases from the California Cancer Registry and used US Census and American Community Survey data to develop multidimensional nSES indices for each census period. We calculated nSES tertile-specific incidence rates and rate ratios for each peri-censal period and used incidence rate ratios (IRR) to assess changes in rates from 1988 to 1992 to 1998-2002 and 2008-2012. RESULTS: There were a total of 231,205 lung cancer cases. Males: Among males, incidence rates of lung cancer decreased over time, all race/ethnicities, and all nSES tertiles, with larger declines among males in higher nSES areas. Rates either declined or were stable for adenocarcinoma, with larger declines for other histologic subtypes. Females: Among females, declines in incidence rates of lung cancer were more pronounced for females in higher nSES areas, but diverged more so than for males, with variations by histology and race/ethnicity. Incidence rates of adenocarcinoma increased over time among all females, with greater increase among females in low nSES areas. CONCLUSIONS: Our findings demonstrate differences in incidence trends over three decades by histology, gender, race/ethnicity, and nSES. While incidence rates consistently declined over time for males, there were greater declines in incidence for high nSES populations. In contrast, among females, there was evidence of increases in lung cancer incidence among low SES API females, and for adenocarcinoma.

Continued Increase in Melanoma Incidence across all Socioeconomic Status Groups in California, 1998-2012.

Melanoma incidence has been increasing in light-skinned populations worldwide, but the reasons for the increase have been controversial. Our prior assessment in California non-Hispanic whites showed substantial increases in invasive melanoma incidence for tumors of all thicknesses in all neighborhoods categorized by socioeconomic status (SES) between 1988-1992 and 1998-2002. To understand whether these trends continued, we updated our assessment to include the diagnosis period 2008-2012 and more accurate pathologic stage at diagnosis. We used the California Cancer Registry to calculate age-adjusted incidence rates for over 58,000 newly diagnosed melanomas. Incidence rates not only continued to rise over the 10-year period from 1998-2002 and 2008-2012 but also showed significant increases in almost all groups defined jointly by tumor thickness or stage at diagnosis and a small area (census tract) SES measure. The largest relative rate increases were seen for regional, distant, and ulcerated disease, especially among males living in the lowest SES neighborhoods. Considering tumor thickness and stage as proxies for time to screening detection and neighborhood SES as a proxy for health care access, we interpret this pattern to indicate continued, true increases in melanoma occurrence as opposed to a thin tumor phenomenon simply driven by improved access to care.

An evaluation of reported no-effect chrysotile asbestos exposures for lung cancer and mesothelioma.

Numerous investigators have suggested that there is likely to be a cumulative chrysotile exposure below which there is negligible risk of asbestos-related diseases. However, to date, little research has been conducted to identify an actual "no-effect" exposure level for chrysotile-related lung cancer and mesothelioma. The purpose of this analysis is to summarize and present all of the cumulative exposure-response data reported for predominantly chrysotile-exposed cohorts in the published literature. Criteria for consideration in this analysis included stratification of relative risk or mortality ratio estimates by cumulative chrysotile exposure. Over 350 studies were initially evaluated and subsequently excluded from the analysis due primarily to lack of cumulative exposure information, lack of information on fiber type, and/or evidence of significant exposures to amphiboles. Fourteen studies meeting the inclusion criteria were found where lung cancer risk was stratified by cumulative chrysotile exposure; four such studies were found for mesothelioma. All of the studies involved cohorts exposed to high levels of chrysotile in mining or manufacturing settings. The preponderance of the cumulative "no-effects" exposure levels for lung cancer and mesothelioma fall in a range of approximately 25-1,000 fibers per cubic centimeter per year (f/cc-yr) and 15-500 f/cc-yr, respectively, and a majority of the studies did not report an increased risk at the highest estimated exposure. Sources of uncertainty in these values include errors in the cumulative exposure estimates, conversion of dust counts to fiber data, and use of national age-adjusted mortality rates. Numerous potential biases also exist. For example, smoking was rarely controlled for and amphibole exposure did in fact occur in a majority of the studies, which would bias many of the reported "no-effect" exposure levels towards lower values. However, many of the studies likely lack sufficient power (e.g., due to small cohort size) to assess whether there could have been a significant increase in risk at the reported no-observed-adverse-effects level (NOAEL); additional statistical analyses are required to address this source of bias and the attendant influence on these values. The chrysotile NOAELs appear to be consistent with exposure-response information for certain cohorts with well-established industrial hygiene and epidemiology data. Specifically, the range of chrysotile NOAELs were found to be consistently higher than upper-bound cumulative chrysotile exposure estimates that have been published for pre-1980s automobile mechanics (e.g., 95th percentile of 2.0 f/ cc-yr), an occupation that historically worked with chrysotile-containing friction products yet has been shown to have no increased risk of asbestos-related diseases. While the debate regarding chrysotile as a risk factor for mesothelioma will likely continue for some time, future research into nonlinear, threshold cancer risk models for chrysotile-related respiratory diseases appears to be warranted.