Review
nature publishing group
Race and Ethnicity in Cancer Therapy: What Have We Learned? C Grenade1,2, MA Phelps1,3 and MA Villalona-Calero1,2 Racial and ethnic disparities in the pathogenesis of common malignancies and outcomes from treatment remain a major health concern. Factors attributed to these disparities include differences in lifestyle, environment, genetics, and tumor biology. As we strive to personalize cancer therapy, it will be imperative that we understand the relative contributions of each factor so that we may apply this knowledge in choosing the best treatment for each individual, regardless of his or her racial or ethnic heritage. Cancer remains a global health-care problem. For the United States, it is estimated that >1.6 million new cancer cases were diagnosed in 2012.1 The National Institutes of Health estimated health-care cost for cancer was $216.6 billion in 2009. Black men are more affected by cancer than any other racial/ethnic group. They have a 14% higher incidence rate and a 34% higher death rate than white men for all cancer sites combined. 2 Cancers of the prostate, lung, and colon are all overrepresented in this group. Furthermore, black women have the highest cancer death rates overall as compared with women in other ethnic groups.1,3 Although US residents of Hispanic ancestry have a lower incidence of the most common cancers (prostate, female breast, lung, and colorectal) as compared with that of non-Hispanic whites, they have a higher burden of infection-associated cancers, including gastric, cervical, and liver cancers. Asians and Pacific Islanders in the United States have lower incidence of most cancers as compared with whites, blacks, and Hispanics, with the notable exception of stomach cancer, the incidence of which is two times higher among Asians/Pacific Islanders as compared with that among whites.1 Factors contributing to these racial/ethnic cancer-related disparities are complex and highly interactive and have been extensively debated in the literature. Differences in socioeconomic, environmental, and biological factors have all been observed, and these differences contribute to racial/ethnic differences in cancer outcomes. Socioeconomic disparities, which limit access to high-quality care, screening/prevention, and timely diagnosis and treatment, undoubtedly contribute to these differences. Genetic variations, such as single-nucleotide polymorphisms (SNPs) occurring in genes responsible for drug-metabolizing
enzymes and drug transporters, have also been shown to exist among different ethnic groups. This can lead to differences in processing, efficacy, and toxicity of cancer treatments. In addition, unique interactions between environmental exposures and the host are probably responsible for the emerging data showing geographical and ethnic differences in somatic driver mutations in tumors such as lung cancer. As cancer therapy and drug development move into the age of identifiable subgroups that would derive optimal benefit from a particular therapy, it is extremely important to consider both inter- and intraethnic variations in tumor molecular composition, anticancer drug disposition, and prevalence of comorbidities that may affect patient tolerance and response to anticancer agents. Yet racial/ ethnic minority patients are usually few in early therapeutic studies and in subsequent clinical trials leading to the approval of these agents. The aim of this review is not to disregard or minimize the tremendous importance of socioeconomic and cultural aspects leading to disparities in health care but to highlight influential biological factors, such as racial/ethnic differences in the pathogenesis and natural history of common malignancies, as well as emerging data in tumor genomics and in the metabolism of anticancer drugs currently approved or in late clinical trials. We note that there are several limitations in categorizations of ethnicities, for blacks, Hispanics/Latinos, and Asians/Pacific Islanders in the United States, because these groups each constitute a diverse mix of people who differ widely in country of origin, immigration patterns, socioeconomic status, lifestyles, and racial mixtures. However, the analysis of racial/ethnic differences from selfidentification is an important first step in identifying critical
1The Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; 2Comprehensive Cancer Center,
The Ohio State University, Columbus, Ohio, USA; 3Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA. Correspondence: MA Villalona-Calero ([email protected]) Received 3 January 2014; accepted 6 January 2014; advance online publication 5 March 2014. doi:10.1038/clpt.2014.5 Clinical pharmacology & Therapeutics | VOLUME 95 NUMBER 4 | april 2014
403
Review clinical variations that could lead to more effective preventative and therapeutic strategies in these underrepresented groups. RACIAL AND ETHNIC DIFFERENCES IN THE PATHOGENESIS AND NATURAL HISTORY OF COMMON CANCERS Lung cancer
US health statistics demonstrate that lung cancer kills more Americans than any other cancer.1 Blacks, in particular, have a 13% overall 5-year survival as compared with 16% in whites, and black men have a 20% higher incidence of lung cancer diagnosis than white men.1 These differences have been attributed to many factors, some related to socioeconomics, environmental influences, and tumor biology. In terms of etiology, tobacco use is still the strongest environmental factor associated with lung cancer cases; thus, racial disparities in tobacco use and smoking patterns are worth close examination. Contrary to popular thinking, blacks initiate smoking later (average age at onset: 17.4 years for blacks vs. 14.7 years for whites).4 In addition, several studies have reported that blacks and Hispanics consume fewer cigarettes per day than whites.4–6 However, more than 70% of black smokers use menthol cigarettes as compared with 30% of white smokers.7 Some studies have reported that smokers of mentholated cigarettes have higher blood nicotine, nicotine metabolite levels, and cotinine levels as compared with nonmenthol smokers.5,8 In addition, other carcinogens, such as blood cadmium levels, have been reported to be higher in those who use menthol cigarettes.9 Racial/ethnic variations in smoking cessation patterns have also been reported, with higher quit rates for whites as compared with blacks and Latinos.6 Available data is conflicting regarding whether mentholated cigarettes enhance tobacco dependence, thus affecting the efficacy of smoking cessation. The stage of cancer at diagnosis is the most important determinant of outcome because surgical resection offers the best chance for cure and can only be performed in localized disease. It has been shown that blacks are less likely to have surgical resection when they present with localized disease.10–12 Cykert et al. reported surgical rates for localized lung cancer of 66% for whites as compared with 55% for blacks. These numbers were even lower in patients with two or more comorbid illnesses (13% for blacks vs. 62% for whites) and when patients lacked a primary-care provider (42% for blacks vs. 57% for whites).10 Unfortunately, this trend has been confirmed in many studies. Lathan et al., for example, showed that only 67% of blacks were given recommendations for lung cancer surgery as compared with 71.4% of whites, and black patients were more likely to refuse surgery once it was recommended.13 Some have suggested that miscommunication between race-discordant patients and physicians could lead to these choices.13,14 Black patients also have higher rates of advanced-stage disease at presentation. Gadgeel et al., examining the Surveillance, Epidemiologic, and End Results (SEER) database, reported that in the past 25 years, the proportion of black patients presenting with advanced-stage disease increased from 44 to 53%, whereas within the same time period the change for whites was from 42 to 48%.15 The increase in the proportion of advanced-stage disease for both groups is 404
thought to be due to the higher sensitivity and availability of staging modalities. Other elements besides disparities in staging and access to surgery may also contribute to the difference in outcomes, which was highlighted in a recent study comparing survival after treatment of advanced non–small cell lung cancer in black and white patients participating in phase II or phase III Cancer and Leukemia Group B clinical trials.16 The importance of this evaluation resides in the fact that entry into these trials provides for uniform extent of disease, as well as therapy. The survival patterns for black and white patients were statistically significantly different, 22 and 30% at 1 year, respectively. A multivariate analysis showed that the percentage of patients presenting with >5% weight loss and decreased performance status was statistically significantly higher among black patients. Breast cancer
It is estimated that 232,000 new cases of breast cancer were diagnosed in American women in 2013 and that about 40,000 women died of this disease.1 Racial disparities among breast cancer patients have been well documented and persist despite the improvements in screenings and treatment that have led to a decrease in breast cancer mortality over the past decade.1,17,18 This is particularly troubling for black women, who have a higher mortality rate despite their overall lower incidence of breast cancer as compared with white women (118.4 vs. 127.3 per 100,000, respectively, for the 2006–2010 period). Of note, younger black women (5.0 cm) primary breast tumors than white women and less likely to be diagnosed with the smaller (≤2.0 cm) tumors, which have the highest cure rates.1 In addition, the incidence of triple-negative (TN) breast cancer (absence of estrogen receptor/progesterone receptor and human epidermal growth factor 2 expression), an aggressive breast cancer type that carries a worse prognosis, is higher among blacks.22 For premenopausal black women, the incidence of TN breast cancer is 40% as compared with only 8% for Asians and white women.23 The occurrence of basal-like, a particularly aggressive subtype of TN breast cancer associated with lower survival, is higher among premenopausal black women as compared with white women (39 vs. 16%).22,24,25 These aggressive tumors were characteristically associated with increased mitotic index, higher grade, increased cyclin D expression, and more TP53 mutations.24 VOLUME 95 NUMBER 4 | april 2014 | www.nature.com/cpt
Review Prostate cancer
The American Cancer Society estimated that more than 240,000 new cases of prostate cancer (PCa) would be diagnosed in the United States in 2013.1,3 Black men have an increased incidence of and mortality from PCa. As compared with white men, black men are 63% more likely to be diagnosed with PCa; 236 black and 146.9 white men are diagnosed per 100,000 men per year, according to SEER data.2,3 Black men with PCa have a 2.4-fold greater mortality rate as compared with white men.1 PCa occurs at a younger age in black men, and black patients, presents with a more advanced-stage, higher prostate-specific antigen and Gleason scores at diagnosis.2 In addition, lower prostatectomy rates and higher PSA recurrence after prostatectomy have been reported in black men. In terms of risk factors for the development of PCa, environmental and lifestyle factors have been linked with this disease. Some epidemiological studies have shown that black men are more likely to be obese and have a diet high in saturated fats.26 Consumption of diets high in red meat and deep-fried foods was associated with increased risk for PCa.27 Several other lifestyle factors, such as low exercise and low vitamin D levels, have been linked to black race/ethnicity and PCa outcomes, although the associations are weak, suggesting that more studies are needed. Despite the racial/ethnic differences in tumor biology noted, for PCa. A major contributor to this cancer-related disparity lies in differences in socioeconomic status and access to high-quality care and treatment experienced by underrepresented minorities. This is supported by studies that controlled for socioeconomic factors and found that black men and white men had similar prostate cancer outcomes.28 Cullen et al. conducted a study in an equal-access-to-care system, the military and veteran populations, and did not observe differences in survival across the races, even though black patients had higher Gleason scores and PSA levels than white patients.29 Colorectal cancer
As the third leading cause of cancer deaths in both men and women, colorectal cancer (CRC) affects ~142,000 individuals, with more than 50,000 deaths in 2013.1 Screening for CRC with colonoscopy, which allows for the detection and removal of colorectal polyps before they progress to cancer, has resulted in a decrease in the incidence and mortality of this malignancy over the past 2 decades. However, racial and ethnic disparities have progressively increased between blacks and whites. Some studies have shown that blacks have lower screening rates as compared with those of whites; differences in socioeconomic status, understanding of physicians’ recommendations, and natural history of CRC are responsible for a great deal of these differences. When common variations in socioeconomic status factors are controlled, as in an equal-access system such as in a veterans medical center, this disparity decreases.30 Blacks have a higher incidence of CRC, are more likely to present with advanced-stage disease, and are more likely to die of their disease regardless of stage at diagnosis.31,32 Chien et al. reported that blacks were more likely to present with stage III or IV CRC.33 By contrast, Asian Americans have a lower incidence Clinical pharmacology & Therapeutics | VOLUME 95 NUMBER 4 | april 2014
of CRC and tend to survive their disease longer than members of other ethnic groups. Lieberman et al. reported that asymptomatic blacks undergoing screening colonoscopy were more likely to have one or more polyps (>9 mm). Black women had a 62% greater risk of having polyps of this size as compared with whites. The authors further reported that black men had a 16% chance of having large polyps as compared with white men.34 Racial/ethnic variations in the anatomical location of CRC have also been noted. Some studies have reported an increase in right-sided or proximal CRC in blacks as compared with whites. The pathogenesis and the contribution of this to observed disparity remain unclear.35 Differences in environmental factors such as diet, vitamin D and exercise have also been reported as explanations for the racial/ethnic variation in CRC outcomes, but conflicting data exist. Racial/ethnic variations in treatment for CRC also exist. Black patients are less likely than whites to receive surgical treatment for stage I and IV CRC. One study reports surgical resection rates of 86 vs. 91% (P = 0.02) for blacks and whites, respectively.31 In addition, differences in the administration of neoadjuvant and adjuvant chemotherapy have been reported and undoubtedly affect outcomes. INFECTION-ASSOCIATED CANCERS
Infections with certain viruses and bacteria have been identified as a strong risk factor for specific cancers. Although these cancers are less common in the United States, they are associated with marked ethnic disparities and are therefore worth mentioning. Stomach, cervical, and liver cancers are malignancies associated with an infectious source and are disproportionately higher among Hispanics and Asian Americans. Stomach/gastric cancer
The incidence and mortality for stomach cancer has decreased in the United States in the past several decades, with most cases now occurring in the gastroesophageal junction and cardia. However, in certain populations, a relatively high risk remains overall, especially for distal stomach cancers. Hispanics/Latinos are disproportionately affected by stomach cancer. According to the American Cancer Society, Hispanic-American men have a 70% higher incidence rate as compared with non-Hispanic white men. For Hispanic women, the rate is doubled compared with that in non-Hispanic white women.1 Younger Hispanics (
nature publishing group
Race and Ethnicity in Cancer Therapy: What Have We Learned? C Grenade1,2, MA Phelps1,3 and MA Villalona-Calero1,2 Racial and ethnic disparities in the pathogenesis of common malignancies and outcomes from treatment remain a major health concern. Factors attributed to these disparities include differences in lifestyle, environment, genetics, and tumor biology. As we strive to personalize cancer therapy, it will be imperative that we understand the relative contributions of each factor so that we may apply this knowledge in choosing the best treatment for each individual, regardless of his or her racial or ethnic heritage. Cancer remains a global health-care problem. For the United States, it is estimated that >1.6 million new cancer cases were diagnosed in 2012.1 The National Institutes of Health estimated health-care cost for cancer was $216.6 billion in 2009. Black men are more affected by cancer than any other racial/ethnic group. They have a 14% higher incidence rate and a 34% higher death rate than white men for all cancer sites combined. 2 Cancers of the prostate, lung, and colon are all overrepresented in this group. Furthermore, black women have the highest cancer death rates overall as compared with women in other ethnic groups.1,3 Although US residents of Hispanic ancestry have a lower incidence of the most common cancers (prostate, female breast, lung, and colorectal) as compared with that of non-Hispanic whites, they have a higher burden of infection-associated cancers, including gastric, cervical, and liver cancers. Asians and Pacific Islanders in the United States have lower incidence of most cancers as compared with whites, blacks, and Hispanics, with the notable exception of stomach cancer, the incidence of which is two times higher among Asians/Pacific Islanders as compared with that among whites.1 Factors contributing to these racial/ethnic cancer-related disparities are complex and highly interactive and have been extensively debated in the literature. Differences in socioeconomic, environmental, and biological factors have all been observed, and these differences contribute to racial/ethnic differences in cancer outcomes. Socioeconomic disparities, which limit access to high-quality care, screening/prevention, and timely diagnosis and treatment, undoubtedly contribute to these differences. Genetic variations, such as single-nucleotide polymorphisms (SNPs) occurring in genes responsible for drug-metabolizing
enzymes and drug transporters, have also been shown to exist among different ethnic groups. This can lead to differences in processing, efficacy, and toxicity of cancer treatments. In addition, unique interactions between environmental exposures and the host are probably responsible for the emerging data showing geographical and ethnic differences in somatic driver mutations in tumors such as lung cancer. As cancer therapy and drug development move into the age of identifiable subgroups that would derive optimal benefit from a particular therapy, it is extremely important to consider both inter- and intraethnic variations in tumor molecular composition, anticancer drug disposition, and prevalence of comorbidities that may affect patient tolerance and response to anticancer agents. Yet racial/ ethnic minority patients are usually few in early therapeutic studies and in subsequent clinical trials leading to the approval of these agents. The aim of this review is not to disregard or minimize the tremendous importance of socioeconomic and cultural aspects leading to disparities in health care but to highlight influential biological factors, such as racial/ethnic differences in the pathogenesis and natural history of common malignancies, as well as emerging data in tumor genomics and in the metabolism of anticancer drugs currently approved or in late clinical trials. We note that there are several limitations in categorizations of ethnicities, for blacks, Hispanics/Latinos, and Asians/Pacific Islanders in the United States, because these groups each constitute a diverse mix of people who differ widely in country of origin, immigration patterns, socioeconomic status, lifestyles, and racial mixtures. However, the analysis of racial/ethnic differences from selfidentification is an important first step in identifying critical
1The Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; 2Comprehensive Cancer Center,
The Ohio State University, Columbus, Ohio, USA; 3Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA. Correspondence: MA Villalona-Calero ([email protected]) Received 3 January 2014; accepted 6 January 2014; advance online publication 5 March 2014. doi:10.1038/clpt.2014.5 Clinical pharmacology & Therapeutics | VOLUME 95 NUMBER 4 | april 2014
403
Review clinical variations that could lead to more effective preventative and therapeutic strategies in these underrepresented groups. RACIAL AND ETHNIC DIFFERENCES IN THE PATHOGENESIS AND NATURAL HISTORY OF COMMON CANCERS Lung cancer
US health statistics demonstrate that lung cancer kills more Americans than any other cancer.1 Blacks, in particular, have a 13% overall 5-year survival as compared with 16% in whites, and black men have a 20% higher incidence of lung cancer diagnosis than white men.1 These differences have been attributed to many factors, some related to socioeconomics, environmental influences, and tumor biology. In terms of etiology, tobacco use is still the strongest environmental factor associated with lung cancer cases; thus, racial disparities in tobacco use and smoking patterns are worth close examination. Contrary to popular thinking, blacks initiate smoking later (average age at onset: 17.4 years for blacks vs. 14.7 years for whites).4 In addition, several studies have reported that blacks and Hispanics consume fewer cigarettes per day than whites.4–6 However, more than 70% of black smokers use menthol cigarettes as compared with 30% of white smokers.7 Some studies have reported that smokers of mentholated cigarettes have higher blood nicotine, nicotine metabolite levels, and cotinine levels as compared with nonmenthol smokers.5,8 In addition, other carcinogens, such as blood cadmium levels, have been reported to be higher in those who use menthol cigarettes.9 Racial/ethnic variations in smoking cessation patterns have also been reported, with higher quit rates for whites as compared with blacks and Latinos.6 Available data is conflicting regarding whether mentholated cigarettes enhance tobacco dependence, thus affecting the efficacy of smoking cessation. The stage of cancer at diagnosis is the most important determinant of outcome because surgical resection offers the best chance for cure and can only be performed in localized disease. It has been shown that blacks are less likely to have surgical resection when they present with localized disease.10–12 Cykert et al. reported surgical rates for localized lung cancer of 66% for whites as compared with 55% for blacks. These numbers were even lower in patients with two or more comorbid illnesses (13% for blacks vs. 62% for whites) and when patients lacked a primary-care provider (42% for blacks vs. 57% for whites).10 Unfortunately, this trend has been confirmed in many studies. Lathan et al., for example, showed that only 67% of blacks were given recommendations for lung cancer surgery as compared with 71.4% of whites, and black patients were more likely to refuse surgery once it was recommended.13 Some have suggested that miscommunication between race-discordant patients and physicians could lead to these choices.13,14 Black patients also have higher rates of advanced-stage disease at presentation. Gadgeel et al., examining the Surveillance, Epidemiologic, and End Results (SEER) database, reported that in the past 25 years, the proportion of black patients presenting with advanced-stage disease increased from 44 to 53%, whereas within the same time period the change for whites was from 42 to 48%.15 The increase in the proportion of advanced-stage disease for both groups is 404
thought to be due to the higher sensitivity and availability of staging modalities. Other elements besides disparities in staging and access to surgery may also contribute to the difference in outcomes, which was highlighted in a recent study comparing survival after treatment of advanced non–small cell lung cancer in black and white patients participating in phase II or phase III Cancer and Leukemia Group B clinical trials.16 The importance of this evaluation resides in the fact that entry into these trials provides for uniform extent of disease, as well as therapy. The survival patterns for black and white patients were statistically significantly different, 22 and 30% at 1 year, respectively. A multivariate analysis showed that the percentage of patients presenting with >5% weight loss and decreased performance status was statistically significantly higher among black patients. Breast cancer
It is estimated that 232,000 new cases of breast cancer were diagnosed in American women in 2013 and that about 40,000 women died of this disease.1 Racial disparities among breast cancer patients have been well documented and persist despite the improvements in screenings and treatment that have led to a decrease in breast cancer mortality over the past decade.1,17,18 This is particularly troubling for black women, who have a higher mortality rate despite their overall lower incidence of breast cancer as compared with white women (118.4 vs. 127.3 per 100,000, respectively, for the 2006–2010 period). Of note, younger black women (5.0 cm) primary breast tumors than white women and less likely to be diagnosed with the smaller (≤2.0 cm) tumors, which have the highest cure rates.1 In addition, the incidence of triple-negative (TN) breast cancer (absence of estrogen receptor/progesterone receptor and human epidermal growth factor 2 expression), an aggressive breast cancer type that carries a worse prognosis, is higher among blacks.22 For premenopausal black women, the incidence of TN breast cancer is 40% as compared with only 8% for Asians and white women.23 The occurrence of basal-like, a particularly aggressive subtype of TN breast cancer associated with lower survival, is higher among premenopausal black women as compared with white women (39 vs. 16%).22,24,25 These aggressive tumors were characteristically associated with increased mitotic index, higher grade, increased cyclin D expression, and more TP53 mutations.24 VOLUME 95 NUMBER 4 | april 2014 | www.nature.com/cpt
Review Prostate cancer
The American Cancer Society estimated that more than 240,000 new cases of prostate cancer (PCa) would be diagnosed in the United States in 2013.1,3 Black men have an increased incidence of and mortality from PCa. As compared with white men, black men are 63% more likely to be diagnosed with PCa; 236 black and 146.9 white men are diagnosed per 100,000 men per year, according to SEER data.2,3 Black men with PCa have a 2.4-fold greater mortality rate as compared with white men.1 PCa occurs at a younger age in black men, and black patients, presents with a more advanced-stage, higher prostate-specific antigen and Gleason scores at diagnosis.2 In addition, lower prostatectomy rates and higher PSA recurrence after prostatectomy have been reported in black men. In terms of risk factors for the development of PCa, environmental and lifestyle factors have been linked with this disease. Some epidemiological studies have shown that black men are more likely to be obese and have a diet high in saturated fats.26 Consumption of diets high in red meat and deep-fried foods was associated with increased risk for PCa.27 Several other lifestyle factors, such as low exercise and low vitamin D levels, have been linked to black race/ethnicity and PCa outcomes, although the associations are weak, suggesting that more studies are needed. Despite the racial/ethnic differences in tumor biology noted, for PCa. A major contributor to this cancer-related disparity lies in differences in socioeconomic status and access to high-quality care and treatment experienced by underrepresented minorities. This is supported by studies that controlled for socioeconomic factors and found that black men and white men had similar prostate cancer outcomes.28 Cullen et al. conducted a study in an equal-access-to-care system, the military and veteran populations, and did not observe differences in survival across the races, even though black patients had higher Gleason scores and PSA levels than white patients.29 Colorectal cancer
As the third leading cause of cancer deaths in both men and women, colorectal cancer (CRC) affects ~142,000 individuals, with more than 50,000 deaths in 2013.1 Screening for CRC with colonoscopy, which allows for the detection and removal of colorectal polyps before they progress to cancer, has resulted in a decrease in the incidence and mortality of this malignancy over the past 2 decades. However, racial and ethnic disparities have progressively increased between blacks and whites. Some studies have shown that blacks have lower screening rates as compared with those of whites; differences in socioeconomic status, understanding of physicians’ recommendations, and natural history of CRC are responsible for a great deal of these differences. When common variations in socioeconomic status factors are controlled, as in an equal-access system such as in a veterans medical center, this disparity decreases.30 Blacks have a higher incidence of CRC, are more likely to present with advanced-stage disease, and are more likely to die of their disease regardless of stage at diagnosis.31,32 Chien et al. reported that blacks were more likely to present with stage III or IV CRC.33 By contrast, Asian Americans have a lower incidence Clinical pharmacology & Therapeutics | VOLUME 95 NUMBER 4 | april 2014
of CRC and tend to survive their disease longer than members of other ethnic groups. Lieberman et al. reported that asymptomatic blacks undergoing screening colonoscopy were more likely to have one or more polyps (>9 mm). Black women had a 62% greater risk of having polyps of this size as compared with whites. The authors further reported that black men had a 16% chance of having large polyps as compared with white men.34 Racial/ethnic variations in the anatomical location of CRC have also been noted. Some studies have reported an increase in right-sided or proximal CRC in blacks as compared with whites. The pathogenesis and the contribution of this to observed disparity remain unclear.35 Differences in environmental factors such as diet, vitamin D and exercise have also been reported as explanations for the racial/ethnic variation in CRC outcomes, but conflicting data exist. Racial/ethnic variations in treatment for CRC also exist. Black patients are less likely than whites to receive surgical treatment for stage I and IV CRC. One study reports surgical resection rates of 86 vs. 91% (P = 0.02) for blacks and whites, respectively.31 In addition, differences in the administration of neoadjuvant and adjuvant chemotherapy have been reported and undoubtedly affect outcomes. INFECTION-ASSOCIATED CANCERS
Infections with certain viruses and bacteria have been identified as a strong risk factor for specific cancers. Although these cancers are less common in the United States, they are associated with marked ethnic disparities and are therefore worth mentioning. Stomach, cervical, and liver cancers are malignancies associated with an infectious source and are disproportionately higher among Hispanics and Asian Americans. Stomach/gastric cancer
The incidence and mortality for stomach cancer has decreased in the United States in the past several decades, with most cases now occurring in the gastroesophageal junction and cardia. However, in certain populations, a relatively high risk remains overall, especially for distal stomach cancers. Hispanics/Latinos are disproportionately affected by stomach cancer. According to the American Cancer Society, Hispanic-American men have a 70% higher incidence rate as compared with non-Hispanic white men. For Hispanic women, the rate is doubled compared with that in non-Hispanic white women.1 Younger Hispanics (
