Research
ajog.org
GYNECOLOGY
Foreign- vs US-born Asians and the association of type I uterine cancer Elise Simons, MD; Kevin Blansit, BS; Torie Tsuei; Rebecca Brooks, MD; Stefanie Ueda, MD; Daniel S. Kapp, MD, PhD; John K. Chan, MD OBJECTIVE: The purpose of this study was to determine the association of
type I endometrioid uterine cancer in US-born vs immigrant Asian women. STUDY DESIGN: Data were obtained from the Surveillance, Epidemiology, and End Results Program from 2001-2009. Chi-squared, Kaplan-Meier, and binomial logistic regression analyses were used for statistics. RESULTS: Of 4834 Asian women with uterine cancer, 62% were USborn and 38% were immigrants. Of these women, 2972 (61%) had type I (grade 1 or 2, endometrioid histologic type) uterine cancer. Compared with patients with type II disease (grade 3, clear cell and serous histologic type), patients with type I disease were younger (age 55 vs 59 years; P < .01) and had lower stage disease (90% vs 71%; P < .01). US-born Asian women had a significantly higher proportion of type I uterine cancers in contrast to their immigrant counterparts (65%
vs 56%; P < .01). Of all immigrants, the proportion of type I cancers was lowest in Japanese women followed by Chinese and Filipino women, respectively (48% vs 52% vs 58%; P < .01). The 5-year diseasespecific survivals of US-born vs immigrant Asian women with type I cancer was 92% for both groups. Over 3 time periods (2001-2003, 2004-2006, and 2007-2009), there was an increase in type I cancers among US-born Asian women (61% to 65% to 68%; P < .01). CONCLUSION: US-born Asian women are more likely to be diagnosed
with type I uterine cancer compared with immigrants. Over the study period, there was a trend towards an increase in type I cancers among US-born Asian women. Key words: Asian, birthplace, endometrial cancer, ethnicity, type I cancer
Cite this article as: Simons E, Blansit K, Tsuei T, et al. Foreign- vs US-born Asians and the association of type I uterine cancer. Am J Obstet Gynecol 2015;212:43.e1-6.
U
terine cancer is the most common gynecologic malignancy. In 2014, there were an estimated 52,630 new cases and an associated 8590 deaths.1 Approximately 7400 cases were diagnosed in Asian women.2 According to the US Census Bureau, the Asian population has grown by 3% per year, and a large majority were immigrants.3 Although a previous study from our group compared the survival of Asian women with white women with uterine cancer, there is limited information regarding the outcomes of subgroups of
US-born and immigrant Asian women with this disease.4 Type I uterine cancers are comprised primarily of low-grade (grades 1 and 2) endometrioid adenocarcinomas. These tumors are associated with unopposed estrogen stimulation and are influenced by diet and environmental exposures. Studies have shown that patients with type I uterine cancer are typically younger with a higher body mass index.5-8 Some authors have hypothesized that an Asian diet, as opposed to the high-caloric and fat Western diet, may contribute to lower rates of
From the Division of Gynecologic Oncology, Department of Obstetrics, Gynecology & Reproductive Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, School of Medicine, San Francisco (Drs Simons, Brooks, Ueda, and Chan, Mr Blansit, and Ms Tsuei); Division of Gynecologic Oncology, California Pacific and Palo Alto Medical Foundation Sutter Research Institute, Palo Alto (Mr Blansit and Dr Chan); and Department of Radiation Oncology, Stanford Cancer Center, Stanford University, Stanford (Dr Kapp), CA. Received April 7, 2014; revised May 21, 2014; accepted July 11, 2014. Supported by the Dr John A. Kerner and Denise Cobb Hale Research Funds. The authors report no conflict of interest. Presented at the 45th annual meeting on Women’s Cancer of the Society of Gynecologic Oncology, Tampa, FL, March 22-25, 2014. Corresponding author: John K. Chan, MD. [email protected] 0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.07.019
endometrial cancer and better survival.9-13 Conversely, patients with type II uterine cancer typically were seen at an older age, with higher grade tumor (grade 3), and aggressive histologic cell types (clear cell and serous histologic types). These tumors are often linked to genetic predisposition, predominantly serous carcinomas, and are associated with poorer prognosis.5-7 The association between race and uterine cell types has been examined previously. Previous studies have shown that African American women are more likely to be diagnosed with poorer prognostic cell types compared with white women.14,15 Moreover, a previous report from our group demonstrated that Asian women were seen at a younger age and earlier stage, with favorable histologic condition, and have better survival vs white women.4 Migration status may also influence the types of cancer. For example, US-born Asian women have a higher incidence of breast, uterine, and ovarian cancer compared with their immigrant counterparts.16-18 Although the influence of migratory status has been explored, few reports have analyzed the difference among
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various Asian ethnic groups, particularly in relation to type I endometrioid uterine cancer.19 In this current study, we compared the proportion of type I uterine cancer in US-born vs immigrant Asian women and within various Asian ethnic groups.
M ETHODS Demographic, clinicopathologic, and treatment data from 2001-2009 were accessed on March 8, 2013, from the Surveillance, Epidemiology and End Results database of the United States National Cancer Institute. Because the Surveillance, Epidemiology and End Results database is a nationwide deidentified database, our study was not covered by an Institutional Review Board application. Data were reported from 9 population-based registries that comprise approximately 14% of the US population that includes Utah, Hawaii, Iowa, New Mexico, Connecticut, and Alaska and the metropolitan cities of Detroit (MI), San Francisco/Oakland (CA), Seattle (WA), Atlanta (GA), San Jose/Monterey (CA), and Los Angeles (CA). Similar to a previous report, we defined Asian race as Chinese, Filipino, Japanese, Korean, South-East Asian, and Indian. Given the small sample size of certain groups, we incorporated the Islander women with the Filipino women. We determined US birth status and Asian subgroups by using selfreported demographic information as previously described.19 We elected to define type I cancers as grade 1 or 2 endometrioid adenocarcinomas and type II as grade 3 endometrioid, clear cell, and serous histology based on the American Cancer Society designation.20 Demographic, clinicopathologic, and treatment data, which included differences in age and stage of disease, were compared with the use of the chi-squared, t-test, and multivariate binomial logistic regression analysis. Survival analysis by age, stage, and migration status were performed with the use of Kaplan-Meier estimates. Factors in the multivariate model included age at diagnosis and birthplace (US-born vs immigrant). A 2-tailed probability value of < .05 was considered statistically significant. Statistical analyses were performed
ajog.org with R statistical software (version 2.15.2; R Foundation for Statistical Computation; Vienna, Austria).
R ESULT Of the 4834 women of Asian descent, the median age was 56 years (range, 19e96 years); the majority of the women (62%) were born in the United States (Table 1). Filipino, Chinese, and Japanese patients comprised the largest ethnic groups at 48%, 16%, and 15%, respectively. Indian, South-East Asian, and Korean populations comprised the remainder of the women. Of patients with staging information, 64% of patients had stage III disease, and 12% had stage III-IV disease. Sixty-one percent of all patients were diagnosed with type I cancer, and the remaining 39% had type II cancers. Compared with patients with type II disease, patients with type I cancer were younger (age, 55 vs 59; P < .01) and had lower stage disease (90% vs 71%; P
5-year survival rate over advancedstage cancers (94% vs 73%; P < .01). The survival rate of US-born vs immigrant Asian women with type I cancer was 92% for both groups (Figure 3). Of note, migration status (US-born vs immigrant) was no longer a predictor for survival after adjustment for other demographic and clinicopathologic factors. Additionally, we investigated changes in the types of uterine cancer over 3 time periods (2001-2003, 2004-2006, and 2007-2009). The proportion of type I cancers did not vary over our study period (62% to 62% to 61%, respectively; P ¼ .75) or with US Census Defined Divisions (West, 52%; Northeast, 62%; South, 56%; West, 62%; P ¼.26). We did not identify any significant change that was based on age at presentation (54 to 54 to 55 years, respectively; P ¼.09) but found a decrease in the proportion of advancedstage disease (11% to 5% to 8%, respectively; P < .01). Over time, there was an increase in type I cancers among US-born women (61% to 65% to 68%, respectively; P < .01) and a decrease in type I cancers in their immigrant counterparts (39% to 35% to 32%, respectively; P < .01; Figure 4).
Proportion of type I endometrioid uterine cancer based on migratory status and ethnicity (n [ 2972)
C OMMENT
FIGURE 1
Proportion of type I endometrioid uterine cancer in US-born vs immigrant Asian women (n [ 4834)
Simons. Type 1 uterine cancer in foreign- vs US-born Asian women. Am J Obstet Gynecol 2015.
of type I cancer compared with other immigrant ethnic groups. In comparison to other US-born Asian women, the USborn Japanese women reported the highest proportion of type I uterine cancers of any group. Across all ethnic groups, US-
born women had a higher proportion of type I cancers compared with their immigrant counterparts (Table 2). On multivariate analysis, United States vs other birthplace (hazard ratio, 1.51; 95% confidence interval, 1.33e1.70; P < .01)
Proportion of type I cancer, n (%) Ethnicity
Total (n [ 4834)
US-born (n [ 1936)
Immigrants (n [ 1036)
P value
Filipino
1289 (62)
743 (66)
546 (58)
< .01
Chinese
462 (58)
278 (63)
184 (51)
< .01
Japanese
469 (65)
422 (67)
47 (48)
< .01
Southeast Asiana
161 (55)
100 (62)
62 (51)
—
Indiana
162 (57)
62 (56)
99 (53)
—
96 (57)
36 (55)
60 (59)
—
Korean a
a
Data not compared because of low numbers (n et al 60% across all ethnic groups of US-born Asian women (Figure 2). It is possible that migrating to the US and adopting the Western lifestyle decreases the protective effects of certain Asian diets and results in similar risks of diet-related cancers among all US-born Asian subgroups. The increase in type I uterine cancer in US-born Asian women warrants prospective evaluation with an emphasis on diet and environmental exposures. There are several limitations in our analyses that may influence the interpretation of our findings. This is a retrospective analysis of data that were collected from a population database that lacked important information such as family history, genetics, diet, body mass index, and physical activity. We also do not have knowledge of comorbid conditions, which include hypertension and diabetes mellitus. Our data did not address reproductive factors, such as age at menarche, number of pregnancies, age of menopause, and documentation of hysterectomy for benign disease. Moreover, we do not have information on the use of medications, including exogenous estrogens, progestins, metformin, and tamoxifen. Our migratory data do not account for the timing, duration, and geographic region of immigrants. Moreover, we were unable to differentiate the number of successive generations of the US-born Asian women. In this report, we limited the type I uterine cancer to those with grade 1 or 2 endometrioid cancers, based on definition adopted by the cancer society and other authorities.5-9,20 However, the exclusion of grade 3 endometrioid cancers from type I disease is not accepted widely.41 Additionally, self-reported birthplace and race cannot describe complex ethnic backgrounds and exposures accurately. A previous study on population-based cancer registries by Gomez et al42 reported on the biases because of incomplete documentation of birthplace in Asian subgroups. Nevertheless, the strength of our study lies
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in the large number of patients with broad racial distribution that allowed us to perform detailed, stratified analyses without limiting statistical power. Given this sample size, we were able to evaluate distinct subgroups within this heterogeneous population of Asian patients. This is one of few studies to report on an unselected group of patients that spanned 12 US regions. The study group of nonselected patients minimizes the biases that often are associated with single-institution reports. Most importantly, the United States contains one of the highest concentrations of Asian women immigrants outside of Asia, which allows investigators to compare disease patterns and trends of immigrants to their US-born cohorts. Overall, our data revealed that US-born Asian women were more likely to be diagnosed with type I immigrant uterine cancer compared with their immigrant counterparts. Japanese women had the lowest proportion of type I cancers compared with other ethnic groups. Over the study period, there was a trend towards an increase in type I cancers among US-born Asian women. Further prospective studies are warranted to evaluate the impact of diet and other environmental exposures on the risk of the development of type I uterine cancer. -
REFERENCES 1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29. 2. Siegel R, Naishadhim D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29. 3. United States Census Bureau. Asians fastest-growing race or ethnic group in 2012, Census Bureau Reports. 2013. 4. Zhang MM, Cheung MK, Osann K, et al. Improved survival of Asians with corpus cancer compared with whites: an analysis of underlying factors. Obstet Gynecol 2006;107:329-35. 5. Sherman ME. Theories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol 2000;13:295-308. 6. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983;15: 10-7. 7. Hecht JL, Mutter GL. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 2006;24:4783-91. 8. Emons G, Fleckenstein G, Hinney B, Huschmand A, Heyl W. Hormonal interactions in endometrial cancer. Endocr Relat Cancer 2000;7:227-42.
ajog.org 9. Goodman MT, Hankin JH, Wilkens LR, et al. Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Res 1997;57: 5077-85. 10. Goodman MT, Wilkens LR, Hankin JH, Lyu LC, Wu AH, Kolonel LN. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 1997;146: 294-306. 11. Horn-Ross PL, John EM, Lee M, et al. Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am J Epidemiol 2001;154:434-41. 12. Suzuki T, Matsuo K, Tsunoda N, et al. Effect of soybean on breast cancer according to receptor status: a case-control study in Japan. Int J Cancer 2008;123:1674-80. 13. Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol 2013;31:2607-18. 14. Allard JE, Maxwell GL. Race disparities between black and white women in the incidence, treatment, and prognosis of endometrial cancer. Cancer Control 2009;16:53-6. 15. Sherman ME, Devesa SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. Cancer 2003;98:176-86. 16. Tominaga S. Cancer incidence in Japanese in Japan, Hawaii, and western United States. Natl Cancer Inst Monogr 1985;69:83-92. 17. Haenszel W, Kurihara M. Studies of Japanese migrants: I, mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst 1968;40:43-68. 18. Lee J, Demissie K, Lu SE, Rhoads GG. Cancer incidence among Korean-American immigrants in the United States and native Koreans in South Korea. Cancer Control 2007;14:78-85. 19. Gomez SL, Clarke CA, Shema SJ, Chang ET, Keegan TH, Glaser SL. Disparities in breast cancer survival among Asian women by ethnicity and immigrant status: a population-based study. Am J Public Health 2010;100:861-9. 20. Society AC. What is endometrial cancer? 02/03/201. 21. Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet 2005;366:491-505. 22. Yang K, HD RZ, Yu X, et al. Abstracts presented for the 41st Annual Meeting of the Society of Gynecologic Oncologists: a validation study of type I vs type II uterine cancer in the Society of Gynecologic Oncologist. San Francisco: Gynecologic Oncology 2010. 23. Terry PD, Rohan TE, Franceschi S, Weiderpass E. Cigarette smoking and the risk of endometrial cancer. Lancet Oncol 2002;3: 470-80. 24. Caserta D, Maranghi L, Mantovani A, Marci R, Maranghi F, Moscarini M. Impact of endocrine disruptor chemicals in gynaecology. Hum Reprod Update 2008;14:59-72. 25. Saxena SP, Khare C, Farooq A, Murugesan K, Buckshee K, Chandra J. DDT and its metabolites in leiomyomatous and normal human uterine tissue. Arch Toxicol 1987;59:453-5.
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26. Gomez SL, Noone AM, Lichtensztajn DY, et al. Cancer incidence trends among Asian American populations in the United States, 1990-2008. J Natl Cancer Inst 2013;105:1096-110. 27. Whittemore AS, Wu-Williams AH, Lee M, et al. Diet, physical activity, and colorectal cancer among Chinese in North America and China. J Natl Cancer Inst 1990;82:915-26. 28. Wakai K, Hirose K, Matsuo K, et al. Dietary risk factors for colon and rectal cancers: a comparative case-control study. J Epidemiol 2006;16:125-35. 29. Freudenheim JL, Graham S, Marshall JR, Haughey BP, Wilkinson G. A case-control study of diet and rectal cancer in western New York. Am J Epidemiol 1990;131:612-24. 30. Popkin BM, Udry JR. Adolescent obesity increases significantly in second and third generation U.S. immigrants: the National Longitudinal Study of Adolescent Health. J Nutr 1998;128:701-6. 31. Gomez SL, Kelsey JL, Glaser SL, Lee MM, Sidney S. Immigration and acculturation in relation to health and health-related risk factors among specific Asian subgroups in a health maintenance organization. Am J Public Health 2004;94:1977-84. 32. Lv N, Cason KL. Dietary pattern change and acculturation of Chinese Americans in Pennsylvania. J Am Diet Assoc 2004;104:771-8. 33. Oza-Frank R, Cunningham SA. The weight of US residence among immigrants: a systematic review. Obes Rev 2010;11:271-80. 34. Van Hook J, Balistreri KS. Immigrant generation, socioeconomic status, and economic development of countries of origin: a longitudinal study of body mass index among children. Soc Sci Med 2007;65:976-89. 35. Dixit AA, Azar KM, Gardner CD, Palaniappan LP. Incorporation of whole, ancient grains into a modern Asian Indian diet to reduce the burden of chronic disease. Nutr Rev 2011;69: 479-88. 36. Levi F, Franceschi S, Negri E, La Vecchia C. Dietary factors and the risk of endometrial cancer. Cancer 1993;71:3575-81. 37. Klatsky AL, Armstrong MA. Cardiovascular risk factors among Asian Americans living in northern California. Am J Public Health 1991;81:1423-8. 38. National Heart L, and Blood Institute. Cardiovascular Risk in the Filipino Community. 2010. 39. Kolonel LN, Henderson BE, Hankin JH, et al. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol 2000;151:346-57. 40. Zhou BF, Stamler J, Dennis B, et al. Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: the INTERMAP study. J Hum Hypertens 2003;17:623-30. 41. Felix AS, Weissfeld JL, Stone RA, et al. Factors associated with type I and type II endometrial cancer. Cancer Causes Control 2010;21:1851-6. 42. Gomez SL, Glaser SL, Kelsey JL, Lee MM. Bias in completeness of birthplace data for Asian groups in a population-based cancer registry (United States). Cancer Causes Control 2004;15:243-53.
ajog.org
GYNECOLOGY
Foreign- vs US-born Asians and the association of type I uterine cancer Elise Simons, MD; Kevin Blansit, BS; Torie Tsuei; Rebecca Brooks, MD; Stefanie Ueda, MD; Daniel S. Kapp, MD, PhD; John K. Chan, MD OBJECTIVE: The purpose of this study was to determine the association of
type I endometrioid uterine cancer in US-born vs immigrant Asian women. STUDY DESIGN: Data were obtained from the Surveillance, Epidemiology, and End Results Program from 2001-2009. Chi-squared, Kaplan-Meier, and binomial logistic regression analyses were used for statistics. RESULTS: Of 4834 Asian women with uterine cancer, 62% were USborn and 38% were immigrants. Of these women, 2972 (61%) had type I (grade 1 or 2, endometrioid histologic type) uterine cancer. Compared with patients with type II disease (grade 3, clear cell and serous histologic type), patients with type I disease were younger (age 55 vs 59 years; P < .01) and had lower stage disease (90% vs 71%; P < .01). US-born Asian women had a significantly higher proportion of type I uterine cancers in contrast to their immigrant counterparts (65%
vs 56%; P < .01). Of all immigrants, the proportion of type I cancers was lowest in Japanese women followed by Chinese and Filipino women, respectively (48% vs 52% vs 58%; P < .01). The 5-year diseasespecific survivals of US-born vs immigrant Asian women with type I cancer was 92% for both groups. Over 3 time periods (2001-2003, 2004-2006, and 2007-2009), there was an increase in type I cancers among US-born Asian women (61% to 65% to 68%; P < .01). CONCLUSION: US-born Asian women are more likely to be diagnosed
with type I uterine cancer compared with immigrants. Over the study period, there was a trend towards an increase in type I cancers among US-born Asian women. Key words: Asian, birthplace, endometrial cancer, ethnicity, type I cancer
Cite this article as: Simons E, Blansit K, Tsuei T, et al. Foreign- vs US-born Asians and the association of type I uterine cancer. Am J Obstet Gynecol 2015;212:43.e1-6.
U
terine cancer is the most common gynecologic malignancy. In 2014, there were an estimated 52,630 new cases and an associated 8590 deaths.1 Approximately 7400 cases were diagnosed in Asian women.2 According to the US Census Bureau, the Asian population has grown by 3% per year, and a large majority were immigrants.3 Although a previous study from our group compared the survival of Asian women with white women with uterine cancer, there is limited information regarding the outcomes of subgroups of
US-born and immigrant Asian women with this disease.4 Type I uterine cancers are comprised primarily of low-grade (grades 1 and 2) endometrioid adenocarcinomas. These tumors are associated with unopposed estrogen stimulation and are influenced by diet and environmental exposures. Studies have shown that patients with type I uterine cancer are typically younger with a higher body mass index.5-8 Some authors have hypothesized that an Asian diet, as opposed to the high-caloric and fat Western diet, may contribute to lower rates of
From the Division of Gynecologic Oncology, Department of Obstetrics, Gynecology & Reproductive Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, School of Medicine, San Francisco (Drs Simons, Brooks, Ueda, and Chan, Mr Blansit, and Ms Tsuei); Division of Gynecologic Oncology, California Pacific and Palo Alto Medical Foundation Sutter Research Institute, Palo Alto (Mr Blansit and Dr Chan); and Department of Radiation Oncology, Stanford Cancer Center, Stanford University, Stanford (Dr Kapp), CA. Received April 7, 2014; revised May 21, 2014; accepted July 11, 2014. Supported by the Dr John A. Kerner and Denise Cobb Hale Research Funds. The authors report no conflict of interest. Presented at the 45th annual meeting on Women’s Cancer of the Society of Gynecologic Oncology, Tampa, FL, March 22-25, 2014. Corresponding author: John K. Chan, MD. [email protected] 0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.07.019
endometrial cancer and better survival.9-13 Conversely, patients with type II uterine cancer typically were seen at an older age, with higher grade tumor (grade 3), and aggressive histologic cell types (clear cell and serous histologic types). These tumors are often linked to genetic predisposition, predominantly serous carcinomas, and are associated with poorer prognosis.5-7 The association between race and uterine cell types has been examined previously. Previous studies have shown that African American women are more likely to be diagnosed with poorer prognostic cell types compared with white women.14,15 Moreover, a previous report from our group demonstrated that Asian women were seen at a younger age and earlier stage, with favorable histologic condition, and have better survival vs white women.4 Migration status may also influence the types of cancer. For example, US-born Asian women have a higher incidence of breast, uterine, and ovarian cancer compared with their immigrant counterparts.16-18 Although the influence of migratory status has been explored, few reports have analyzed the difference among
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various Asian ethnic groups, particularly in relation to type I endometrioid uterine cancer.19 In this current study, we compared the proportion of type I uterine cancer in US-born vs immigrant Asian women and within various Asian ethnic groups.
M ETHODS Demographic, clinicopathologic, and treatment data from 2001-2009 were accessed on March 8, 2013, from the Surveillance, Epidemiology and End Results database of the United States National Cancer Institute. Because the Surveillance, Epidemiology and End Results database is a nationwide deidentified database, our study was not covered by an Institutional Review Board application. Data were reported from 9 population-based registries that comprise approximately 14% of the US population that includes Utah, Hawaii, Iowa, New Mexico, Connecticut, and Alaska and the metropolitan cities of Detroit (MI), San Francisco/Oakland (CA), Seattle (WA), Atlanta (GA), San Jose/Monterey (CA), and Los Angeles (CA). Similar to a previous report, we defined Asian race as Chinese, Filipino, Japanese, Korean, South-East Asian, and Indian. Given the small sample size of certain groups, we incorporated the Islander women with the Filipino women. We determined US birth status and Asian subgroups by using selfreported demographic information as previously described.19 We elected to define type I cancers as grade 1 or 2 endometrioid adenocarcinomas and type II as grade 3 endometrioid, clear cell, and serous histology based on the American Cancer Society designation.20 Demographic, clinicopathologic, and treatment data, which included differences in age and stage of disease, were compared with the use of the chi-squared, t-test, and multivariate binomial logistic regression analysis. Survival analysis by age, stage, and migration status were performed with the use of Kaplan-Meier estimates. Factors in the multivariate model included age at diagnosis and birthplace (US-born vs immigrant). A 2-tailed probability value of < .05 was considered statistically significant. Statistical analyses were performed
ajog.org with R statistical software (version 2.15.2; R Foundation for Statistical Computation; Vienna, Austria).
R ESULT Of the 4834 women of Asian descent, the median age was 56 years (range, 19e96 years); the majority of the women (62%) were born in the United States (Table 1). Filipino, Chinese, and Japanese patients comprised the largest ethnic groups at 48%, 16%, and 15%, respectively. Indian, South-East Asian, and Korean populations comprised the remainder of the women. Of patients with staging information, 64% of patients had stage III disease, and 12% had stage III-IV disease. Sixty-one percent of all patients were diagnosed with type I cancer, and the remaining 39% had type II cancers. Compared with patients with type II disease, patients with type I cancer were younger (age, 55 vs 59; P < .01) and had lower stage disease (90% vs 71%; P
5-year survival rate over advancedstage cancers (94% vs 73%; P < .01). The survival rate of US-born vs immigrant Asian women with type I cancer was 92% for both groups (Figure 3). Of note, migration status (US-born vs immigrant) was no longer a predictor for survival after adjustment for other demographic and clinicopathologic factors. Additionally, we investigated changes in the types of uterine cancer over 3 time periods (2001-2003, 2004-2006, and 2007-2009). The proportion of type I cancers did not vary over our study period (62% to 62% to 61%, respectively; P ¼ .75) or with US Census Defined Divisions (West, 52%; Northeast, 62%; South, 56%; West, 62%; P ¼.26). We did not identify any significant change that was based on age at presentation (54 to 54 to 55 years, respectively; P ¼.09) but found a decrease in the proportion of advancedstage disease (11% to 5% to 8%, respectively; P < .01). Over time, there was an increase in type I cancers among US-born women (61% to 65% to 68%, respectively; P < .01) and a decrease in type I cancers in their immigrant counterparts (39% to 35% to 32%, respectively; P < .01; Figure 4).
Proportion of type I endometrioid uterine cancer based on migratory status and ethnicity (n [ 2972)
C OMMENT
FIGURE 1
Proportion of type I endometrioid uterine cancer in US-born vs immigrant Asian women (n [ 4834)
Simons. Type 1 uterine cancer in foreign- vs US-born Asian women. Am J Obstet Gynecol 2015.
of type I cancer compared with other immigrant ethnic groups. In comparison to other US-born Asian women, the USborn Japanese women reported the highest proportion of type I uterine cancers of any group. Across all ethnic groups, US-
born women had a higher proportion of type I cancers compared with their immigrant counterparts (Table 2). On multivariate analysis, United States vs other birthplace (hazard ratio, 1.51; 95% confidence interval, 1.33e1.70; P < .01)
Proportion of type I cancer, n (%) Ethnicity
Total (n [ 4834)
US-born (n [ 1936)
Immigrants (n [ 1036)
P value
Filipino
1289 (62)
743 (66)
546 (58)
< .01
Chinese
462 (58)
278 (63)
184 (51)
< .01
Japanese
469 (65)
422 (67)
47 (48)
< .01
Southeast Asiana
161 (55)
100 (62)
62 (51)
—
Indiana
162 (57)
62 (56)
99 (53)
—
96 (57)
36 (55)
60 (59)
—
Korean a
a
Data not compared because of low numbers (n et al 60% across all ethnic groups of US-born Asian women (Figure 2). It is possible that migrating to the US and adopting the Western lifestyle decreases the protective effects of certain Asian diets and results in similar risks of diet-related cancers among all US-born Asian subgroups. The increase in type I uterine cancer in US-born Asian women warrants prospective evaluation with an emphasis on diet and environmental exposures. There are several limitations in our analyses that may influence the interpretation of our findings. This is a retrospective analysis of data that were collected from a population database that lacked important information such as family history, genetics, diet, body mass index, and physical activity. We also do not have knowledge of comorbid conditions, which include hypertension and diabetes mellitus. Our data did not address reproductive factors, such as age at menarche, number of pregnancies, age of menopause, and documentation of hysterectomy for benign disease. Moreover, we do not have information on the use of medications, including exogenous estrogens, progestins, metformin, and tamoxifen. Our migratory data do not account for the timing, duration, and geographic region of immigrants. Moreover, we were unable to differentiate the number of successive generations of the US-born Asian women. In this report, we limited the type I uterine cancer to those with grade 1 or 2 endometrioid cancers, based on definition adopted by the cancer society and other authorities.5-9,20 However, the exclusion of grade 3 endometrioid cancers from type I disease is not accepted widely.41 Additionally, self-reported birthplace and race cannot describe complex ethnic backgrounds and exposures accurately. A previous study on population-based cancer registries by Gomez et al42 reported on the biases because of incomplete documentation of birthplace in Asian subgroups. Nevertheless, the strength of our study lies
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Research
Gynecology
in the large number of patients with broad racial distribution that allowed us to perform detailed, stratified analyses without limiting statistical power. Given this sample size, we were able to evaluate distinct subgroups within this heterogeneous population of Asian patients. This is one of few studies to report on an unselected group of patients that spanned 12 US regions. The study group of nonselected patients minimizes the biases that often are associated with single-institution reports. Most importantly, the United States contains one of the highest concentrations of Asian women immigrants outside of Asia, which allows investigators to compare disease patterns and trends of immigrants to their US-born cohorts. Overall, our data revealed that US-born Asian women were more likely to be diagnosed with type I immigrant uterine cancer compared with their immigrant counterparts. Japanese women had the lowest proportion of type I cancers compared with other ethnic groups. Over the study period, there was a trend towards an increase in type I cancers among US-born Asian women. Further prospective studies are warranted to evaluate the impact of diet and other environmental exposures on the risk of the development of type I uterine cancer. -
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