Cancers

Epidemiology of Aging: Racial/Ethnic Specifi c Disease Prevalence

8.3.2 Cancers

8.3.2.1 Prostate Cancer

According to the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) registry, age-adjusted prostate cancer incidence among men 65 years and older remains highest in AAs (AA), 814 per 100,000), as compared to NHWs (NHWs, 547), Hispanics (522), American Indian/Alaska Natives (AIANs, 371) and Asians and Pacifi c Islanders (APIs, 370 per 100,000) (National Cancer Institute Fast Stats). In fact, Brawley notes that prostate cancer incidence rates among AA men and Jamaican men of African descent are the highest in the world, and while the causes for this has not been entirely elucidated, it appears that differ- ences in socioeconomic status (SES) mediate a substantial part of the increased risk [ 16 ]. Prostate cancer incidence sharply declined by over 12 % per year between

2010 and 2012 when combining men over 65 years of all racial/ethnic groups, with most individual groups showing similar rates of decline, except for AIANs who have experienced a slower, more consistent decline since 1992 (SEER Fast Stats).

And while mortality among men 65 years and older with prostate cancer continues to decline steadily in all racial/ethnic groups, large disparities remain. Age-adjusted mortality among AAs was highest (194 per 100,000) followed by NHWs (170), AIAN (152), Hispanics (118), and APIs (104 per 100,000). Much of AAs’ excess mortality is attributable to socioeconomic status, though differences in treatment of comparable prostate cancers between AAs and Whites have been documented for more than two decades, with the former consistently receiving less aggressive care despite evidence of likely equal benefi t from equal therapies [ 16 ].

Schreiber et al. identifi ed 1794 AA and White men with low-volume, low-risk cancers who met the following criteria: diagnosis between 2010 and 2011, stage T1cN0M0, Gleason score of 6 (3 + 3) at biopsy, PSA <10 ng/mL, no more than two positive samples on a 12-core biopsy, and status postradical prostatectomy [ 17 ]. The AA men were found to be a median of 3 years younger and were signifi cantly more likely to have two positive cores, but no difference between whites and AAs was found regarding Gleason score on surgical pathology, pathologic extent of disease, surgical margins, Cancer of the Prostate Risk Assessment Score, or other adverse pathological features. The authors concluded that among AA and White men with very low-risk prostate cancer, there was no evidence to suggest that either race had more aggressive features at the time of surgical resection, but gave a nod to other investigators’ work suggesting genetic and biochemical factors leading to more aggressive cancers in AAs, including androgen receptor expression, epidermal growth factor receptor ( EGFR ) expression, metastasis-associated protein 1, and other differences in gene expression between cancers of the two racial groups.

In a study of disease severity, treatment, and survival in the SEER cancer regis- tries in Asian American and Pacifi c Islanders (AAPI), Chao and colleagues noted that AAPI were more likely to present with advanced prostate cancer but had better cancer-specifi c survival [ 18 , 19 ]. Hawaiians, Filipinos, Asian Indian/Pakistani, and Pacifi c Islanders were more likely to present with metastasis than NHWs after mul- tivariable multinomial regression analysis. Japanese, Hawaiians, and Koreans had the highest odds of receiving defi nitive treatment and Filipino men were less likely.

Hawaiian and Pacifi ca Islander men had higher prostate cancer specifi c mortality risk at 19.34 and 16.63 % when compared to NHWs. Hawaiians were almost twice as likely at 10.9 %, to present with metastasis than NHWs, 5.49 %. Chao and col- leagues further discuss possible cause of prostate cancer incidence and mortality by hypothesizing differences in testosterone, diet, access to health care, language belief systems regarding a cancer diagnosis, and the possibility of developing prostate cancer at lower prostate-specifi c antigen (PSA) levels. The reasons for the better survival are not really known. The heterogeneity of the group belies reliance on genetic factors for this improved survival [ 18 , 19 ].

The American Cancer Society notes that prostate cancer is the most common cancer among Hispanic men [ 20 ]. The incidence is about 9 % lower than NHWs and decreased at a higher rate of 4.7 % per year versus 3.5 %, and death rate is lower,

17.8 per 100,000 versus 19.9. Hispanic men and NHW men have roughly compa- rable diagnosis at a localized stage, 75 % compared to 79 % and survival rate at a distant stage, 32 % compared to 29 %. Haile and colleagues note that the genetically heterogeneous background of many Hispanics, age and family history or prostate cancer in fi rst-degree relatives as probable and more defi nite contributors in any possible disparities.

Latini and colleagues compared clinical characteristics and disease-free survival between AA, Hispanic, and NHW males (the article uses the terms Latino and non- Latino White instead) [ 21 ]. The study used the Cancer of the Prostate Strategic Urologic Research Endeavor study (CaPSURE), which is a longitudinal, observa- tional disease registry for men with biopsy-proven prostate cancer. The analysis found Gleason scores and PSA levels were higher at the time of diagnosis for AA men compared to Hispanics and NHWs. Hispanics and AAs presented with the same amount of advanced disease but less than NHWs, 10 % versus 4 %. These results differ from the American Cancer Society data. There were not statistically signifi cant differences in treatment type for Hispanics and NHWs; however, AA men appeared to receive more external beam radiation and hormone treatment than NHWs. The study showed no differences in disease-free survival between NHWs and Hispanics (83 % and 86 %, respectively) but did fi nd differences in disease recurrence following radical prostatectomy.

8.3.2.2 Breast Cancer

Breast cancer mortality has been overall improving over the last 25 years and Desantis notes the decline might be associated with the decreased use of menopausal hormones and increased mammography screening [ 22 ]. Despite this improvement, AA women are diagnosed with breast cancer at earlier ages and more aggressive features when compared to other racial and ethnic groups [ 22 ]. SEER data shows that 127.3 White women per 100,000 are diagnosed with breast cancer every year versus 118.4 per 100,000 Black or AA women. The differences extend to mortality with 30.8 versus 22.7 rate of mortality [ 22 ]. In addition, the risk of breast cancer is higher in Hispanics born in the United States than foreign-born Hispanics [ 5 ].

An analysis of the National Cancer Data Base between 2010 and 2011 notes dif- ferences in hormone receptor subtypes [ 23 ]. Compared to NHWs, Blacks and Hispanics were 85 % and 17 % more likely to have Hr−/HER2− (TN) subtypes ver- sus HR+/HER2−, respectively. This study also found APIs had 1.45 greater odds of diagnosis with a HER2− overexpressing subtype than HR+/HER2− subtype in NHWs. This study represents an effort to expand genetic studies beyond those with European ancestry. A genome-wide association study examined the interaction between genetic ancestry and hormonal and lifestyle factors for Hispanic women.

This study did a partial correlation between genetic ancestry, hormone replacement, and breastfeeding behavior that explains some breast cancer risk difference in Hispanics [ 24 ].

Treatment delays are thought to contribute to the increased morbidity and mor- tality of breast cancer in AAs and Hispanics [ 25 ]. Parson and colleagues investi- gated this theory and other differences that might contribute to morbidity and mortality disparities. Hispanics represented 50 % of this study population. Those with breast cancer that were Hispanic but non-White were more likely to also be overweight and obese. Non-Hispanic Whites and Hispanics were less likely to have estrogen and progesterone receptor negative status than other groups. Hispanics were also more likely to have some impairment in functional status (described as an Eastern Cooperative Oncology Group Performance Status [ECOG] greater or equal to 1) and a higher histological grade at diagnosis. There was no signifi cant differ- ence in time to biopsy from abnormal mammogram or from biopsy to treatment initiation after adjustment for age, cancer/treatment characteristics, and sociodemo- graphics [ 25 ], Parsons postulates that the lack of difference might be due to access to a National Cancer Institute designated center and impact of cultural infl uence in a patient and provider population majority. As discussed in Chap. 10 , belief differ- ence might also infl uence accessing health care for a diagnosis and treatment behavior.

Farias and colleagues explored differences in initiation and timing of adjuvant endocrine therapy [ 26 ]. The study determined that Asian women have greater odds compared to NHW women, odds ratio: 1.28, 95 % CI: 1.03–1.58. Tamoxifen initia- tion odds were lower with Hispanic Mexicans and non-Hispanic AAs (0.70, 0.54–

0.91; 0.25, 0.10–0.62) and Hispanic Mexicans and Asians (2.06, 1.34–3.10; 1.33, 1.11–1.61) had higher odds of aromatase initiation. Asians were the only group with greater odds of adjuvant endocrine therapy initiation compared to NHWs.

According to Cancer Facts and Figures, there are signifi cant differences in breast cancer within the AANHPI (AANHPI) population and incidence has been rising since 2005 (Cancer Facts and Figures 2016). Some of these differences might be attributed to time since immigration, associated western behavior adoption of age at childbirth, fewer numbers of births and higher body weight, and possibly differ- ences in tumor characteristics. The lowest incidence rates are in Cambodian women at 35 per 100,000 and the highest rates are among Native Hawaiians at 135.9 per 100,000. Survival rates are higher in Japanese Americans. Interestingly, the associa- tion of disease states and breast cancer risk was explored in a population-based Taiwanese study [ 27 ]. This study noted obesity, endometriosis, uterine leiomyoma, hypertensive diseases, and disorders of lipid metabolism, many of these being estro- gen-related factors, to be associated with breast cancer risk. This association might be able to be applied to all racial and ethnic groups to varying degrees and might also explain some of the differences between and within groups.

According to Chuang and colleagues, there are differences in the distribution of cancer subtypes in Asian subgroups [ 28 ]. Chinese and Japanese had a higher pro- portion of luminal A cancers compared to Filipinos and Koreans. Filipinos had a higher proportion of Her-2/neu positive and Koreans had a higher proportion of triple negative cancers. Therefore, there is a potential that some of these differences could explain signifi cant differences in cancer incidence and survival.

8.3.2.3 Colon Cancer

In a review published by Jackson and colleagues, an examination of health dispari- ties in colorectal cancer by ethnicity was performed [ 29 ]. Signifi cant disparities were found in colorectal cancer screening, age of diagnosis, treatment, and out- comes between different ethnicities. When health care access differences are elimi- nated, similar colon cancer survival has been noted [ 30 ]. This was particularly true for individuals 50 years old and older. Colorectal cancer disparities can be evaluated based on screening differences, family history-related health education, and care following screening [ 29 ].

As noted, differences in screening exist. Although Blacks and Hispanics had increased compliance with testing when there is a family history; Layiyemo and colleagues found that Blacks and Hispanics were less likely to be compliant than Whites without a family history [ 31 ]. Jackson and colleagues noted many additional challenges including that AAs were more likely to be diagnosed at a younger age, often before the screening age recommendation of age 50, and had a decreased likelihood of knowing a paternal cancer history or have an inaccurate cancer family history [ 29 ]. AAPIs overall had a lower screening rate when compared to NHWs with Koreans demonstrating the lowest screening rate and Japanese the highest.

The American Cancer Society notes that Asian Americans, Native Hawaiians, and Pacifi c Islander males and females have a lower incidence of death, 20 and 30 % lower than NHWs [ 32 ]. This category is quite diverse and there are differences in colorectal cancer incidence with Japanese Americans having three times the inci- dence of Asian Indians/Pakistanis and differences between US-born and foreign- born Chinese and Filipino individuals. The probability of developing invasive cancer in AANHPI male and females is 1.2 % and 0.8 %, respectively, for those 60–69 and 3.9 and 3.5 % for those 70 and older. Notably, incidence colorectal can- cer is lowest in AANHPI males and females at 39.9 and 30, respectively, and highest among American Indian/Alaska Native males 50.9 and Non-Hispanic Black females at 45.6.

Robbins and colleagues examined the SEER data for mortality differences between Blacks and Whites in stage-specifi c cancer [ 33 ]. The data examined covered from 1985 to 2008. There was a decrease in mortality for both groups, but Whites experienced the greater decline with 30.5 % versus 13.2 % for localized stage, 48.5 % versus 34 % for regional stage, and 32.6 % versus 32.5 % for distant stage. The differ- ence in the distant stage is most striking. In addition, signifi cant 5-year survival rate differences for regional and distant stage became consistently lower for Blacks in 1990 and 2002 but the localized stage survival was similar. Whites experienced an improvement in survival for regional disease but Blacks did not.

The incidence of colorectal cancer in Hispanics is decreasing overall; however, there has been some increase in those younger than 50 (this applies to all racial and ethnic groups) [ 29 ]. There is signifi cant variability within this group, with Puerto Ricans living in Puerto Rico and immigrant Mexican Americans with lower inci- dence than NHWs. In addition, incidence rates for colorectal cancer for those from

the Dominican Republic, Spain, and other Central and South American Speaking nations were equivalent or greater than non-Hispanic Whites.

8.3.2.4 Lung Cancer

Lung cancer is a heterogeneous disease comprised of several histological types, with three being most common: adenocarcinoma (43.3 %), squamous cell carci- noma (22.6 %), and small cell carcinoma (13.3 %) per National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) data from 1975 to 2012 (National Cancer Institute SEER Statistics Review). During this time period, small cell cancers were most common in AIANs (18.1 % of all lung cancers) and least so among APIs (7.8 %), with intermediate percentages in Whites, Hispanics, and AAs. APIs had the highest percentage of adenocarcinoma (58.1 %) and AIANs the lowest (33.3 %). Squamous cell cancers had the highest frequency in AIANs (24.8 %) and were least frequent among APIs (15.5 %). Recent, notable trends high- lighted by Lewis and colleagues and Patel and colleagues for the years leading up to 2011 include: overall decline in lung cancer incidence rates among males and level- ing off among females across racial/ethnic groups; more rapid decreases in squa- mous and small cell carcinoma among White and AA males than in females;

decreases in squamous and small cell carcinoma among APIs and Hispanics of both sexes with converging rates among Whites and AAs; climbing adenocarcinoma rates among females (especially Hispanic and AA) with stable rates or minimal decline in males; across-the-board decrease in “unspecifi ed carcinomas” refl ecting, in part, better pathology techniques for classifi cation [ 34 , 35 ].

In 2012, overall incidence of lung cancer among those 65 years and older was 323 per 100,000 persons (National Cancer Institute Fast Stats). The highest incidence group (among those 65 years and older) was NHWs with 355 per 100,000, followed by AA with 334, APIs with 217, AIANs with 204, and Hispanics with 177 per 100,000.

Since data for APIs, AIANs, and Hispanics was included beginning in 1992, rates remained fairly steady across ethnic groups in those aged 65 years and older with the same ordering until roughly 2008, when rates among NHWs and AA began to fall: by 10 % and 11 % overall, respectively, from 2008 to 2012. These improvements stem from decline in smoking prevalence over the prior 30 years [ 36 ]. Hispanics represent an exception: they continue along a secular decline in lung cancer incidence compris- ing a 22 % decrease between 1992 and 2012. Rates among AIANs are much more variable owing to sample size (for men, women, and both sexes considered together), without a defi nite trend in the greater than 65 age group. This is not the case when considering AIANs of all ages, for which there is a much clearer trend of falling inci- dence on par with the rate of decrease seen in other racial/ethnic groups.

Among those 65 years and older, incidence rates among AA men steadily fell from 689 to 454 per 100,000 between 1992 and 2012 (a 34 % overall decrease), while incidence among AA women actually rose from 228 to peak at 298 per 100,000 in 2005 before declining gradually to 272 per 100,000 in 2012. Incidence in Asian and Hispanic men have greatly decreased during this time, 21 % and 34 %,

respectively, but Asian women have seen an increase, 9 %, that continues to persist.

There is no change in incidence among Hispanic women. When considering all ages and both sexes, AAs have the highest lung cancer incidence, followed by NHWs, AIANs, APIs, and Hispanics. AAs are more likely to develop lung cancer at an earlier age as compared to Whites even though White adolescents are more likely to be smokers [ 37 ].

Prizment et al. investigated lung cancer incidence among Whites and AAs in the ARIC Study [ 38 ]. After 20 years of follow-up, Whites currently smoking had 22 times the risk of lung cancer as compared to White non-smokers; similarly, AA cur- rent smokers had 13 times the risk of AA non-smokers. White smokers had much greater cumulative tobacco exposure than did AA smokers in this study, and when data was adjusted for baseline pack-years of smoking, hazard ratio of current smok- ers to non-smokers was roughly 9 in both AAs and Whites. No racial differences were found in effects of current smoking status, intensity, or age of initiation on lung cancer risk between Whites and AAs. Moreover, prolonged smoking cessation (greater than 10 years) benefi tted both AAs and Whites greatly, with 74 % and 84 % reduction in lung cancer incidence, respectively.

Lung cancer is the leading cause of cancer-related death in the United States, and the SEER database indicates racial and ethnic differences in mortality rates among patients with lung cancer [ 37 ] (National Cancer Institute Fast Stats). In 2012, among those 65 years and older, mortality was lowest among Hispanics (124 per 100,000), followed by APIs (150), AIANs (242), AAs (274), and NHWs (287 per 100,000).

Mortality rates have been in decline among AAs, Hispanics, and NHWs with lung cancer by an annual percentage change of roughly −2 % since the mid-2000s, while APIs have seen a more steady mortality decline, −0.9 % per year, since 1992.

Mortality among AIANs has, in fact, increased by 0.3 % per year on average since 1992. AAs have shorter overall survival and increased mortality compared to Whites persists after adjustment for socioeconomic status and access to care [ 22 ]. AAs have been found to be less likely than Whites to undergo surgery (which offers the best chance for cure) for early stage disease, and less likely to receive standard of care therapies, even when data is adjusted for socioeconomic factors [ 22 , 36 ].

As cancer treatment has moved to incorporate therapies targeted to an individual cancer’s genetics, there is now an emerging body of work investigating differences in lung cancer mutations by race and the implications for treatment. Epidermal growth factor ( EGFR ) and KRAS mutations represent possible targets for therapy.

They have differential expression in the United States when compared to other countries as well as in individuals with certain lifestyle factors, such as increased EGFR expression in female smokers. Bollig-Fischer and colleagues searched for tumor genetic differences by race at 26 oncogenes and tumor suppressor genes in patients with nonsmall cell lung cancer (NSCLC) [ 37 ]. AAs were 42 % less likely than Whites to have any mutation detected, which translates to fewer targeted thera- pies available, on average. There were signifi cant differences by race in mutations at three genes, c-met , notch 1 , and serine/threonine kinase 11 , which were present in patients’ tumors as well as in germline DNA. AA women were four times more likely than White women to have EGFR exon 19 deletions, while all other loci