From the California Cancer Registry (CCR), which comprises three of the National Cancer Institute’s SEER program registries(8), we obtained information on all California residents diagnosed with a primary invasive lymphoid malignancy (International Classification of Disease for Oncology, 3^rd Edition, (ICD-O-3) morphology codes 9590–9591, 9650–9655, 9661–9734, 9761, 9764, 9823, 9827–9837, 9940, 9948, and 9970) during the period 1 January 1988 through 31 December 2004. Using InterLymph Consortium guidelines (9, 10), we further classified lymphoid malignancies by histologic subtype into diffuse large B-cell lymphoma [DLBCL] (ICD-O-3 morphology codes 9680 and 9684, excluding those with code 9684 and a T-cell, NK-cell or null cell immunophenotype); follicular lymphoma [FL] (codes 9690, 9691, 9695, and 9698); chronic lymphocytic lymphoma/small lymphocytic leukemia [CLL/SLL] (codes 9823 and 9670); multiple myeloma [MM] (codes 9731–9734); classical HL (codes 9650–9655, 9661–9667) and its two most common subtypes, nodular sclerosis [NS] HL (codes 9663–9665, 9667) and mixed cellularity [MS] HL (code 9652); and T- or NK-cell NHL [TCL] (codes 9700–9719, 9729, 9827, 9831, 9834, 9837, and 9948 plus codes 9590, 9591, 9675, 9684, 9727, 9820, 9832, 9835, or 9970 and a T-cell or NK cell immunophenotype). Overall NHL was categorized as including codes 9590–9591, 9670–9729, 9761, 9764, 9820, 9823, 9827, 9831–9837, 9940, 9948, and 9970.

We included in these analyses 8,638 lymphoid malignancies (6,712 NHL, 526 NHL, and 1,410 MM) occurring in patients from the six Asian ethnic populations that together comprised 92% of all Asian and Pacific Islander patients with lymphoid malignancies in the CCR in the study period. Of these, 2,385 (28%) cases were Chinese, 1,246 (14%) were Japanese, 2,913 (34%) were Filipino, 506 (6%) were Korean, 701 (8%) were South Asian (including Asian Indians, Pakistanis, Sri Lankans and Bangladeshis), and 887 (10%) were Vietnamese. Approximately 5% of patients were originally coded in the registry data as “Asian, not otherwise specified (NOS)”; for 55% of these patients, we were able to determine a more specific Asian ethnic designation based on birthplace and names (first, maiden, last) by applying the North American Association of Central Cancer Registries (NAACCR) Asian/Pacific Islander Identification Algorithm (11). We also included as a reference group 110,789 non-Hispanic white patients diagnosed with lymphoid malignancies (85,465 NHL, 8,967 HL, and 16,357 MM) during the same period.

Because patients in the cancer registry with unknown birthplace data are more likely to be US-born than those with available data (3–6), we developed a method based on patients’ Social Security numbers (SSN) to more accurately classify patient immigrant status, as described previously (7). Briefly, we used: 1) registry-based birthplace data available for 81% of cases (73% from hospital medical records and 8% from death certificates); and 2) for the 19% of cases with unknown birthplace, statistical imputation of immigrant status using the patient’s SSN. Comparing the age of SSN issue with self-reported birthplace in previously interviewed cancer patients (N=1,836) and based on maximization of the area under the receiver-operating characteristic curve and confirmation with logistic regression modeling, we considered cases who received an SSN before age 25 years US-born, and those who had received an SSN at or after age 25 years as foreign-born. This age cut-point resulted in 84% sensitivity and 80% specificity for assigning foreign-born status across the Asian populations. Fewer than 3% of cases with missing or invalid SSNs were assigned an immigrant status based on the ethnicity-sex-age birthplace distribution of the overall sample.

Using patient residential address and small area (census tract) information from the US Census, we classified neighborhood SES and ethnic enclave status for all Asian patients diagnosed between 1 January 1998 and 31 December 2002. We considered all Asians together as a single group because detailed ethnicity-specific population estimates are not available for census tracts, and chose the time period in question (i.e., within two years of the 2000 US Census) because census tract estimates are only available for decennial census years. Census tracts were geocoded from patient residential address at time of diagnosis. The 3% of eligible cases whose address could not be precisely geocoded to a census tract were randomly assigned to a census tract within their county of residence. We assigned neighborhood SES using a previously described index (12) that incorporates 2000 Census data on education, income, occupation, and housing costs. We categorized this measure by quintiles based on the distribution of the composite SES index across the state of California, then re-categorized into two groups because of small sample sizes in the quintiles: lower SES (quintiles 1, 2, and 3) or higher SES (quintiles 4 and 5). Because the CCR does not collect any individual-level information on patient SES, we could not assess neighborhood-level effects separately from those at the individual-level.

We defined a neighborhood ethnic enclave as a geographical unit that is relatively more concentrated in terms of its population and language (in this study specific to Asians) than other geographical units in California. To characterize residence in an ethnic enclave, we applied principal components analysis (PCA) (13) to selected census variables at the block group level, which was in turn averaged to the census tract level. The census variables included in the ethnic enclave index were: percent of Asian-language-speaking households that are linguistically isolated, percent of all Asian-language speakers who speak limited English, percent recent immigrants, and percent Asian. This index explained 63% of the variability in the data. Neighborhood ethnic enclave was classified into quintiles based on the distribution of the composite ethnic enclave index across the state of California, then re-categorized into two groups because of small sample sizes in the quintiles: lower (quintiles 1, 2, and 3) or higher (quintiles 4 and 5) enclave status.

From the 1990 and 2000 Census Summary File 3 (SF-3), we obtained population counts by sex, race/ethnicity, immigrant status, and five-year age group for the state of California. We also used data from the 20% Integrated Public-Use Microdata Sample of the Census to estimate age- and birthplace-specific population counts for the six Asian groups (14–17) by smoothing with a spline-based function(18). For intercensal years, we estimated the percent foreign-born using cohort component interpolation and extrapolation methods(19), adjusting estimates to the populations by age and year provided by the California Department of Finance for years 1988–1989 and by the US Census for years 1990–2004 due to data availability.

We used SEER*Stat software (20) to compute age-adjusted incidence rates (standardized to the 2000 US standard million population) and 95% confidence intervals (CIs). To comply with CCR regulations, we do not present case counts or rates based on fewer than 15 cases. For HL, we also calculated age-adjusted rates for persons ages 15–44 (N=159 males, 153 females), and 45 and above (N=110 males, 70 females), at diagnosis) because of strong previous evidence of etiologic differences between these groups (21). We calculated incidence rate ratios (IRRs) to compare incidence rates. Because of small case numbers, Asian ethnic groups were combined for analyses of NHL subtypes, MM, and HL, and analyses of HL rates jointly by SES and enclave could not be undertaken by age group. We could not perform joint analyses by birthplace and neighborhood SES or ethnic enclave status due to the lack of census-tract-level population data by birthplace. All analyses had the approval of the institutional review board of the Cancer Prevention Institute of California.

For NHL overall, age-adjusted incidence rates for most Asian ethnic groups were substantially lower than those for non-Hispanic whites (Table 2). For example, the IRR among foreign-born Filipino males vs. white males was 0.70 (95% CI 0.65–0.75) and the corresponding IRR for females was 0.76 (95% CI 0.70–0.83); the IRR among foreign-born Chinese males vs. white males was 0.49 (95% CI 0.44–0.54) and the corresponding IRR among females was 0.50 (95% CI 0.45–0.55). The only groups for which rates were not significantly different from those of non-Hispanic whites were the relatively small populations of foreign-born Japanese men and US-born South-Asian and Vietnamese men and women.

For most specific lymphoid malignancy subtypes, incidence rates for both US- and foreign-born Asians were lower than those for non-Hispanic whites. The most marked deficits were observed for CLL/SLL (among males, IRR for foreign-born Asians vs. whites=0.22, 95% CI 0.18–0.25; among females, IRR=0.24, 95% CI 0.18–0.30) and NS HL (among males, IRR for foreign-born Asians vs. whites=0.25, 95% CI 0.13–0.37; among females, IRR=0.19, 95% CI 0.13–0.26). However, for TCL and DLBCL (in most ethnic groups), rates were comparable to those for non-Hispanic whites.

For overall NHL, foreign-born Chinese, South Asian, and Vietnamese men and women had consistently lower incidence rates than their US-born counterparts (Table 2). By contrast, foreign-born Japanese men had incidence rates 71% higher than their US-born counterparts, whereas no birthplace difference was observed among Japanese women or Korean men or women.

For specific subtypes, Table 3 shows that FL incidence was consistently lower among foreign-born than US-born Asian men and women. For DLBCL, for which numbers of cases were adequate for examining rates for Chinese and Japanese, patterns were similar to those observed for overall NHL, with lower incidence rates for foreign-born vs. US-born Chinese men and women, in contrast to higher rates among foreign-born vs. US-born Japanese men. Among Japanese and other Asian (Filipina, South Asian, and Vietnamese) women, there were no significant differences in the incidence rate of DLBCL by birthplace. Incidence rates of TCL did not vary by birthplace among Asian men or women. For MM, rates were marginally higher (37%) among foreign-born than US-born Asian women, but comparable by birthplace in men.

For overall HL, rates among foreign-born Asians were approximately half those among US-born Asians. IRR patterns were similar for NS HL, but no nativity differences occurred in rates of MC HL. In data stratified by age, the protective effect of foreign birthplace was limited to young adults of both genders for HL overall; for NS HL, it was apparent for both younger and older females (IRR’s of 0.34 (95% CI 0.23–0.50) for ages 15–44, and 0.32 (95% CI 0.14–0.80) for ages 45 and above).

Although we had limited statistical power for to assess rate changes over time stratified by birthplace, rates did not vary significantly between the periods 1988–1996 and 1997–2004 (data not shown). For overall NHL, rates increased significantly among US-born Chinese and Filipino men and foreign-born Korean men, but not among women of the same groups. IRRs comparing foreign- vs. US-born Asians were generally similar between 1988–1996 and 1997–2004, although for overall HL and NS HL, they were statistically significant only in the latter period (data not shown).

Among Asian men, ethnic enclave status did not impact the incidence rates of overall NHL, DLBCL, FL, CLL/SLL, TCL, MM, overall HL, NS HL, or MC HL (Table 4). By contrast, among Asian women, overall NHL, CLL/SLL, overall HL and MC HL were significantly less common in neighborhoods with higher ethnic enclave status. For HL, these patterns did not differ by age group for either gender. Asian men living in higher-SES neighborhoods had significantly elevated incidence rates of FL and NS HL (an effect limited to young adult men), but not of other lymphoma subtypes. Asian women in higher-SES neighborhoods had significantly higher incidence rates of FL, TCL and overall HL (apparent only for women over age 45 at diagnosis); marginally higher rates of NS HL and MC HL; but lower rates of CLL/SLL.

When we analyzed rates by neighborhood ethnic enclave status and SES jointly, we found that Asian men living in areas with both lower ethnic enclave status and higher SES had significantly higher incidence rates of overall NHL and FL, as well as a marginally higher incidence rate of DLBCL, than Asian men living in areas with both higher enclave status and lower SES (Table 4). For overall HL and NS HL, rates were marginally higher for Asian men living in neighborhoods of higher than lower SES irrespective of their ethnic enclave status. Compared to Asian women living in neighborhoods with both higher ethnic enclave status and lower SES, Asian women living in neighborhoods with lower ethnic enclave status and higher SES also had significantly elevated incidence rates of overall NHL, FL, overall HL and NS HL; elevations were particularly marked for the latter two (IRR=4.1, 95% CI 2.15–7.74, and 2.5, 95% CI 1.17–5.14, respectively). In addition, Asian women who resided in neighborhoods with both higher ethnic enclave status and higher SES had elevated incidence rates of FL, TCL, and overall HL but a lower rate of CLL/SLL. MM incidence rates did not vary by neighborhood enclave status and SES among Asian men or women.