Cancer incidence data came from the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute [2, 3]. During the period covered by this study (2012–2016 for rate and 1999–2016 for trends), tumor histology, tumor behavior, and primary cancer site were coded according to the Third Edition of the International Classification of Disease for Oncology (ICD-O-3) and classified according to SEER site categories [4].

To reduce racial misclassification of AI/AN populations, cancer registry data were linked with the IHS patient registration database by using previously established and validated techniques that improve accuracy of cancer incidence estimates among the AI/AN population [5, 6]. Each year, NPCR- and SEER-funded central registries submit data on cancers diagnosed during the most recent year to the respective program.

Incidence data from registries meeting rigorous quality control standards were combined into an analytic file U.S. Cancer Statistics [7]. By combining these registries, we have 100% coverage of the AI/AN population. To improve racial classification of AI/AN populations, we restricted analyses to purchased/referred care delivery area (PRCDA) counties, which contain, or are adjacent to, federally recognized tribal lands. Restricting to PRCDA counties provides more accurate correction for racial misclassification of the AI/AN population than other counties [5, 6]. Approximately 53% of the AI/AN population resides in these counties (Web Figure 1).

Population estimates that are used as denominators in the rate calculations are produced by the US Census Bureau. In a previous report, the updated, bridged, intercensal population estimates overestimated AI/AN populations of Hispanic origin [8]. In the present study, all analyses were limited to non-Hispanic AI/AN populations to avoid underestimation of incidence rates among the AI/AN population. Non-Hispanic White was chosen as the reference population. For conciseness, the term “non-Hispanic” was omitted when discussing both groups in this study.

Cancer incidence rates for the 15 most common cancers among AI/AN males and females compared to the White population, and their corresponding RRs, are shown in Web Tables 1 and 2. The leading cancers with elevated cancer incidence were selected on the basis of the RR comparing AI/AN versus White incidence rates by sex. Among AI/AN males, the leading cancer sites with elevated incidence were liver, stomach, kidney, colorectal, myeloma, and lung (Figure 1A, Web Table 1). The leading cancers with elevated incidence among AI/AN females included these sites, except for myeloma, and including cervical cancers (Figure 1B, Web Table 2). Rate ratios ranged from 1.09 (lung) to 2.37 (liver) among AI/AN males and 1.06 (lung) to 3.03 (liver) among AI/AN females. The incidence rates were higher among AI/AN males compared to females, ranging from 23% higher for lung cancer, to 129% higher for liver cancer (Figure 2).

Among AI/AN males, the number and type of cancers with elevated incidence varied by region (Table 1). Alaska, the Southern Plains, Southwest, and the Northern Plains had the highest number of cancer types with elevated incidence among the AI/AN population. Rate ratios for cancers with elevated incidence ranged from 1.14 (colorectal cancer in the Southwest) to 4.36 (stomach cancer in Alaska). Liver, stomach, kidney, lung, and colorectal cancers were elevated in most regions, except for lung cancer in the Southwest and liver cancer in Alaska. In the East, only liver cancer was significantly higher among AI/AN males compared to White males. Liver cancer was the leading site with elevated incidence in four of six regions.

Among AI/AN males, the incidence rate of several cancers increased during the study period (Table 1), with some of the largest increases occurring in liver cancers in the East (AAPC 8.1), Southern Plains (AAPC: 6.2), Pacific Coast (AAPC: 4.8) and Northern Plains (AAPC 4.5), and kidney cancers in the Northern Plains (AAPC: 2.9) and Southern Plains (AAPC: 3.1). Significant decreases were observed in colorectal cancer incidence rates in the Northern Plains (AAPC: −1.7) and Pacific Coast (AAPC −2.0).

Among AI/AN females, the Southern Plains, Northern Plains, Alaska, and the Pacific Coast had the most types of cancer with elevated incidence (Table 2). Rate ratios for elevated incidence cancers ranged from 1.15 (corpus and uterus in the Pacific Coast) to 4.07 (stomach in Alaska). Rate ratios for liver cancer ranged from 2.17 in the East and Alaska to 3.63 in the Southwest. Stomach cancer was elevated in every region. Kidney cancer was elevated in 5 of 6 regions (except the East); the highest RR occurred in the Northern Plains (RR = 2.12).

During 2012–2016, stomach cancer incidence rates decreased significantly among AI/AN females in the Northern Plains (AAPC −4.3) (Table 2). Incidence rates of liver cancer increased significantly in the Southern Plains (AAPC: 4.8) and Southwest (AAPC: 3.6). Rates of kidney cancer also increased significantly in the Southern Plains (AAPC: 2.7) and Southwest (AAPC: 2.1). Cancers of the pancreas (AAPC: 2.9), corpus and uterus (AAPC: 1.6), and thyroid (AAPC: 6.6) increased significantly in the Southern Plains; and stomach cancer increased in the East (AAPC: 4.4). Rates of breast cancer also increased in the Southern Plains (AAPC: 1.0).

For the leading sites with elevated incidence among AI/AN males (Table 3), the observed to expected ratios ranged from 1.14 for colorectal cancer in the Pacific Coast to 5.33 for stomach cancer in Alaska. An estimated 2,450 excess cancers were diagnosed among AI/AN males. The largest number of excess cancers among AI/AN males occurred in Southern Plains (727) and some of the highest numbers of excess cancers are attributable to colorectal, lung, and liver cancers.

Among AI/AN females, the observed to expected ratios for the leading causes of elevated cancer incidence (Table 4) ranged from 1.14 (corpus and uterus in the Pacific Coast) to 4.13 (stomach in Alaska). Overall, 2,732 excess cancers were diagnosed among AI/AN females in these 6 regions. The largest number of excess cancers among AI/AN females occurred in the Southern Plains (1198).

This study provides a comprehensive overview of the leading cancer types with elevated incidence among the AI/AN population, by region, for the years 2012–2016. The cancers identified as excess cancers in this study are driving cancer disparities in AI/AN populations and have been shown to contribute to cancer related disparities in other underrepresented populations [13–15]. The present study confirms prior findings that showed substantial regional variation in cancer incidence rates among the AI/AN population [1, 16]. These findings provide further evidence that data aggregated across cancer sites or by region mask important differences in cancer incidence, both within the AI/AN population and between the AI/AN and White population. Liver, stomach, kidney, lung, and colorectal cancers were among the cancers consistently elevated across several regions among the AI/AN population. This study estimated that nearly 5,200 cases of cancer in the AI/AN population were potentially avoidable during 2012–2016 among AI/AN populations in the 6 study areas if racial disparities had not existed in cancer incidence.

Liver cancer was a leading cancer with elevated incidence among AI/AN populations in nearly every region. Incidence rates were as much as four times higher than rates among the White population among both AI/AN males and females, confirming previous findings [17]. The prevalence of hepatitis C virus (HCV) infection, a known risk factor of liver cancer, is higher among the AI/AN population than among the non-Hispanic White population [17, 18]. To increase screening for HCV among the AI/AN population in the Southern Plains, the Cherokee Nation Health Services implemented a clinical decision support tool within the health records for primary care physicians, targeting individuals at high risk of liver cancer. This effort resulted in a nearly 14% increase in the number of eligible individuals receiving HCV screening during 2012–2015, and nearly 90% of the individuals subsequently treated after HCV diagnosis achieved a cure [19]. Other efforts include collaborations between IHS and Project ECHO (Extension for Community Healthcare Outcomes) aimed at improving HCV-related care for the AI/AN population through teleconsulting and “telementoring” partnerships between specialists and providers in rural and underserved communities [20].

This study also confirmed previous findings about the elevated incidence of kidney cancer among the AI/AN population [21]. Increases in kidney cancer incidence have been linked with rising rates of obesity [21–23]. Previous studies suggested that smoking and hypertension may also play roles in elevated kidney cancer rates [24]. These few known risk factors for kidney cancer are unlikely to fully explain the observed geographic variation in kidney cancer incidence, or the elevated incidence rates among the AI/AN population. Additional studies can help better understand the factors driving differences in kidney cancer incidence between the AI/AN and White populations.

Despite ongoing efforts to reduce the high prevalence of commercial tobacco use among AI/AN populations, the present study suggests that lung cancer incidence rates have largely remained stagnant among the AI/AN population. A new Government Performance and Results Act measure was established in 2006 to track tobacco cessation service delivery among current smokers within the IHS and tribal programs [25]. Although this measure has progressively improved each year, from the baseline of 12% in 2006 to over 50% in 2016 [25], the present study suggests that expanding culturally competent tobacco control strategies for the use of commercial tobacco remains an important aspect of cancer prevention among the AI/AN population.

This study confirms persistent disparities in colorectal cancer incidence rates among the AI/AN population. Although decreasing colorectal cancer incidence rates were observed among AI/AN males in the Northern Plains and Pacific Coast regions, rates actually increased among AI/AN males in the Southwest region. There were no significant declines in colorectal cancer incidence rates among AI/AN females in regions with elevated colorectal cancer incidence, suggesting the need to increase screening for this disease. In addition, inequities in colorectal cancer risk factors could be addressed, such as higher diabetes prevalence, lower dietary intake of fruits and vegetables, and higher consumption of sugar sweetened beverages, alcohol, and tobacco products. Collaborative efforts to increase colorectal cancer screening in regions with the highest incidence of disease show promise, but alone they may not be sufficient to eliminate disparities in incidence [26–29].

Although stomach cancer incidence rates for the overall US population are low, rates of stomach cancer among the AI/AN population are high, specifically among the Alaska Native population. The association between stomach cancer and Helicobactor Pylori infection can likely account for a large portion of these increased rates of stomach cancer, specifically in Alaska where the prevalence of infection among the AI/AN population can range from 64% to 81%, and reinfection rates after treatment are as high as 16% [30, 31]. Although Helicobactor Pylori is an important risk factor, infection is not a sufficient cause of stomach cancer [32]. Other environmental and behavioral factors linked with the development of stomach cancer include high intake of salt, nitrites, and nitrates; family history; smoking; and obesity [33–36]. Screening and early detection of stomach cancer may be beneficial to high-risk AI/AN individuals, such as first-degree relatives of persons with stomach cancer, because survival rates after treatment of advanced stage disease are poor [37]. Although screening high-risk populations for stomach cancer is appropriate among countries with relatively high incidence rates, screening is generally thought to be costly and unwarranted because of the low overall burden among countries with low rates of stomach cancer, such as the United States [32]. Studies have shown that data on exposure to risk factors associated with stomach cancer can aid in the identification of high-risk subgroups for more targeted screening and intervention [38, 39]; these strategies might also be effective in Indian country [37].

This study has limitations. To reduce racial misclassification of AI/AN populations, the IHS patient registration database was linked with data from the central cancer registries. However, these linkages only address the racial misclassification for individuals that have previously accessed services through the IHS; thus, AI/AN individuals who are not members of federally recognized tribes are not included. In addition, individuals living in urban, non-PRCDA areas are not represented in these data. Results based on these data may not be generalizable to all AI/AN individuals in the United States. Finally, restriction of the analyses to non-Hispanic AI/AN populations may not accurately represent all AI/AN populations. Although this exclusion reduced overall AI/AN incidence rates by less than 5%, this exclusion may disproportionally affect cancer incidence rates in certain regions. Finally, this study uses data from central cancer registries and does not consider social determinants of health that may affect cancer incidence.

The present study highlights cancers with elevated incidence among the AI/AN compared to the White populations. Elevated incidence in liver, stomach, kidney, lung, and colorectal cancers represent important health inequities between AI/AN and White populations. Areas for improvement for cancer prevention and control among the AI/AN population include efforts to promote healthy environments and address the underlying social determinants of cancer risk. Culturally informed, community-based interventions to support healthy behaviors, reduce exposure to carcinogens, promote recommended screening for cancer or its risk factors, and increase access to preventive health services may reduce these persistent disparities in cancer incidence among the AI/AN population.