Incidence of colorectal cancer (CRC) in younger adults (age < 50 years) is rising in the US [
Understanding differences in sociodemographic and clinicopathologic characteristics of CRC patients by age may provide an important insight into mechanisms that have contributed to increasing incidence of CRC in younger populations. However, most research in this area is limited to single institution settings or clinic-based samples. Findings from these studies generally reflect characteristics of patients treated at that institution. For example, a number of studies [
To address this gap in the literature, we examined demographic, socioeconomic, and clinicopathologic characteristics of younger and older CRC patients in a population-based sample of stages II and III CRC. We limited the study to stages II and III patients because we expected more variation in treatment with chemotherapy and radiation therapy. As a secondary aim, we also examined the receipt of treatment by age.
The study population was derived from the National Cancer Institute’s (NCI) Patterns of Care (POC) studies. The NCI annually conducts POC studies on a random sample of patients with select cancers (e.g., breast [
We examined demographic, clinicopathologic, and socioeconomic characteristics of the study population. Patient demographics included age at diagnosis, sex, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, or others), and insurance (private, Medicare only, any Medicaid, or none).
Clinicopathologic features included tumor site, stage at diagnosis, histologic grade (well/moderately differentiated, poorly/undifferentiated), mucinous or signet ring cell histology, and receipt of microsatellite instability (MSI) testing. Tumor site included right colon (cecum, ascending colon, hepatic flexure, and transverse colon), left colon (splenic flexure, descending colon), sigmoid colon, and rectum (rectosigmoid junction, rectum) according to the International Classification of Disease for Oncology, 3rd Edition (ICD-O-3). Data on MSI were collected in 2010 only.
Socioeconomic indicators were derived from POC, SEER, and the Area Health Resource File (AHRF). POC contains patient-level data on hospital type (private, government, or nonprofit), an approved residency training program, total bed size, and cancer clinical trial enrollment. We also used a composite census-tract index of socioeconomic status based on measures developed by Yost et al. [
Treatment patterns included type of surgery (partial, subtotal, or total colectomy or proctectomy), number of lymph nodes examined (0, 1–11, or ≥12), receipt of chemotherapy, and receipt of radiation therapy (among rectal cancer patients only). As part of POC studies, treatment information was abstracted from medical records and verified by treating physicians. Treating physicians were also asked to provide names and addresses of other physicians who may have treated the patient, who were subsequently contacted for additional treatment details.
Descriptive statistics (e.g., proportions, means) were used to examine the distribution of covariates by age at diagnosis (<50 years, 50–69 years, and ≥70 years). Age categories were chosen in an effort to account for the potential heterogeneity of CRC in older patients (e.g., the CIMP phenotype is most common in female CRC patients aged ≥70 years [
To account for potential differences by race/ethnicity, we conducted a stratified analysis of select covariates in the subgroup of younger (age < 50 years) non-Hispanic white (
We also examined the proportion of patients who received chemotherapy and radiation therapy by tumor site (colon versus rectum), stage at diagnosis, and age. Patients who received therapy or patients for whom it was recommended that they receive therapy but it was unknown whether they did were considered to have received therapy (
Proportions and means were weighted with stratum-specific sample weights to reflect the population (i.e., SEER) from which the sample was drawn. Sample weights were calculated as the inverse of the sampling proportion for each sampling stratum.
All statistical analyses were conducted using SAS version 9.3 (SAS Institute, Cary, NC). Statistical significance was accepted as
A total of 6,862 stages II and III CRC patients were included in the analysis. Characteristics of the study population by age at diagnosis are shown in Table
Characteristics of 6,862 patients diagnosed with stages II and III colorectal cancer, 1990–2010, by age at diagnosis.
Age < 50 years | Age 50–69 years | Age ≥ 70 years | ||||
---|---|---|---|---|---|---|
| Weighted1% | | Weighted1% | | Weighted1% | |
| ||||||
Sex | ||||||
Male | 472 | 54.0 | 1685 | 56.0 | 1377 | 44.3 |
Female | 399 | 46.0 | 1333 | 44.0 | 1596 | 55.7 |
Race/ethnicity | ||||||
White, non-Hispanic | 317 | 61.4 | 1490 | 71.5 | 1810 | 81.0 |
Black, non-Hispanic | 200 | 13.3 | 634 | 11.2 | 449 | 6.7 |
Hispanic | 189 | 14.7 | 495 | 9.7 | 386 | 6.7 |
Other | 165 | 10.5 | 399 | 7.6 | 328 | 5.6 |
Insurance | ||||||
Private/HMO/VA/other | 637 | 78.9 | 2214 | 76.8 | 1848 | 67.2 |
Medicare (only) | 127 | 1.0 | 351 | 9.1 | 685 | 23.0 |
Medicaid (any) | 13 | 14.4 | 254 | 10.6 | 358 | 9.2 |
None | 75 | 5.8 | 128 | 3.6 | 21 | 0.6 |
| ||||||
Tumor site | ||||||
Right colon | 176 | 22.4 | 679 | 31.9 | 951 | 46.4 |
Left colon | 116 | 15.6 | 332 | 15.1 | 379 | 15.4 |
Sigmoid colon | 137 | 25.1 | 536 | 22.2 | 482 | 20.2 |
Rectum2 | 433 | 36.9 | 1456 | 30.8 | 1140 | 18.0 |
Stage at diagnosis | ||||||
Stage II | 360 | 42.2 | 1437 | 48.7 | 1532 | 54.2 |
Stage III | 511 | 57.8 | 1581 | 51.3 | 1441 | 45.8 |
Histologic grade | ||||||
Well/moderately differentiated | 640 | 78.7 | 2352 | 82.2 | 2216 | 73.4 |
Poorly/undifferentiated | 186 | 21.3 | 526 | 17.8 | 641 | 26.6 |
Mucinous adenocarcinoma | 110 | 11.1 | 293 | 9.5 | 321 | 11.5 |
Signet ring cell carcinoma | 12 | 0.8 | 28 | 0.7 | 29 | 1.2 |
MSI testing performed | ||||||
Yes | 68 | 27.3 | 83 | 9.7 | 44 | 7.1 |
No | 140 | 72.7 | 540 | 90.3 | 423 | 92.9 |
Unknown | 23 | 29 | 15 | |||
| ||||||
Surgery type | ||||||
Local excision4 | 6 | 0.7 | 16 | 0.5 | 16 | 0.4 |
Partial colectomy or proctectomy5 | 480 | 56.4 | 1619 | 50.5 | 1466 | 41.1 |
Subtotal colectomy | 240 | 30.7 | 839 | 38.4 | 1080 | 50.6 |
Total colectomy or proctectomy | 98 | 9.1 | 346 | 6.5 | 249 | 3.8 |
Total proctocolectomy | 38 | 2.4 | 163 | 3.4 | 139 | 3.5 |
Other | 9 | 0.7 | 35 | 0.7 | 23 | 0.6 |
Lymph nodes examined | ||||||
0 | 24 | 1.8 | 89 | 2.0 | 73 | 1.7 |
1–11 | 258 | 25.8 | 1302 | 37.8 | 1499 | 45.0 |
≥12 | 560 | 72.4 | 1537 | 60.2 | 1297 | 53.3 |
| ||||||
SES index6 | ||||||
Quintile 1 | 122 | 15.8 | 378 | 18.5 | 322 | 17.2 |
Quintile 2 | 113 | 21.4 | 350 | 20.3 | 279 | 20.6 |
Quintile 3 | 109 | 19.5 | 322 | 24.7 | 259 | 17.5 |
Quintile 4 | 113 | 20.8 | 251 | 16.0 | 276 | 22.2 |
Quintile 5 | 104 | 22.6 | 275 | 20.6 | 238 | 22.6 |
| ||||||
Hospital type | ||||||
Private | 67 | 11.9 | 238 | 7.2 | 247 | 10.1 |
Government | 182 | 16.1 | 540 | 17.4 | 387 | 13.5 |
Nonprofit | 621 | 72.0 | 2212 | 75.4 | 2313 | 76.4 |
Teaching hospital | ||||||
No | 370 | 45.2 | 1397 | 51.9 | 1564 | 53.9 |
Yes | 498 | 54.8 | 1585 | 48.1 | 1374 | 46.1 |
Total bed size | ||||||
<200 | 194 | 26.1 | 676 | 25.1 | 710 | 27.2 |
200–400 | 336 | 39.3 | 1330 | 43.2 | 1335 | 43.6 |
≥400 | 339 | 34.6 | 982 | 31.6 | 895 | 29.2 |
Clinical trial enrollment | ||||||
No | 728 | 91.7 | 2494 | 94.4 | 2583 | 98.2 |
Yes | 67 | 8.3 | 179 | 5.6 | 74 | 1.8 |
VA: Veterans Affairs; MSI: microsatellite instability; SES: socioeconomic status.
1Proportions weighted by sampling fraction.
2The term “rectal” includes both rectum and rectosigmoid junction.
3Microsatellite instability collected in 2010 only.
4Local excision includes excisional biopsy or polypectomy with or without photodynamic therapy, electrocautery, cryosurgery, laser ablation, laser excision, curette, and fulguration.
5Partial proctectomy includes low anterior resection and total mesorectal excision.
6Socioeconomic status based on composite census-tract-level indicators from Census 2000 and American Community Survey 2005–2009; limited to data collection years 2000, 2005, and 2010. Louisiana excluded due to Hurricanes Katrina and Rita’s impact on populations within Gulf Coast region in 2005.
In the analysis of the stratified subset of younger patients by race/ethnicity (Table
Characteristics of 706 younger (age < 50 years) patients diagnosed with stages II and III colorectal cancer, 1990–2010, by race/ethnicity.
NH white | NH black ( | Hispanic ( | ||||
---|---|---|---|---|---|---|
| Weighted1% | | Weighted1% | | Weighted1% | |
Sex | ||||||
Male | 184 | 54.8 | 109 | 52.1 | 94 | 52.7 |
Female | 133 | 45.2 | 91 | 47.9 | 95 | 47.3 |
Insurance | ||||||
Private/HMO/VA/other | 275 | 86.1 | 129 | 60.7 | 114 | 67.7 |
Medicaid (any) | 22 | 10.8 | 48 | 26.1 | 35 | 19.6 |
None | 11 | 3.0 | 16 | 10.5 | 29 | 9.8 |
Tumor site | ||||||
Right colon | 49 | 19.4 | 62 | 38.5 | 42 | 26.3 |
Left colon | 28 | 13.8 | 29 | 19.9 | 29 | 16.4 |
Sigmoid colon | 44 | 25.9 | 29 | 17.8 | 33 | 24.3 |
Rectum | 193 | 40.9 | 80 | 23.8 | 83 | 32.9 |
Mucinous histology | 30 | 10.4 | 36 | 17.7 | 29 | 11.8 |
Histologic grade | ||||||
Well/moderately differentiated | 246 | 80.7 | 146 | 81.7 | 140 | 79.2 |
Poorly/undifferentiated | 57 | 19.3 | 39 | 18.3 | 40 | 20.8 |
Stage at diagnosis | ||||||
Stage II | 118 | 42.7 | 86 | 47.4 | 87 | 38.0 |
Stage III | 199 | 57.3 | 114 | 52.6 | 102 | 62.0 |
MSI testing performed3 | ||||||
Yes | 14 | 25.4 | 20 | 31.6 | 18 | 23.5 |
No | 36 | 74.6 | 32 | 68.4 | 42 | 76.5 |
Unknown | 9 | 1 | 6 | |||
SES index | ||||||
Quintile 1 | 11 | 7.7 | 46 | 37.9 | 45 | 28.0 |
Quintile 2 | 30 | 22.5 | 26 | 24.2 | 34 | 20.9 |
Quintile 3 | 26 | 16.3 | 18 | 16.3 | 30 | 27.4 |
Quintile 4 | 37 | 21.8 | 20 | 16.1 | 25 | 17.0 |
Quintile 5 | 43 | 31.7 | 12 | 5.4 | 8 | 6.7 |
NH: non-Hispanic; VA: Veterans Affairs; MSI: microsatellite instability; SES: socioeconomic status.
1Proportions weighted by sampling fraction.
2Percentages do not add to 100 because some younger patients were insured through Medicare; cell sizes too small (<5) to report.
3MSI testing collected in 2010 only.
4Socioeconomic status based on composite census-tract-level indicators from Census 2000 and American Community Survey 2005–2009; limited to study years 2000, 2005, and 2010 and not including Louisiana.
Differences in county-level socioeconomic indicators by age at diagnosis are shown in Table
County-level socioeconomic indicators of 6,862 patients diagnosed with stages II and III colorectal cancer, 1990–2010, by age at diagnosis.
Age < 50 years | Age 50–69 years | Age ≥ 70 years | ||||
---|---|---|---|---|---|---|
| Weighted1% | | Weighted1% | | Weighted1% | |
Per capita income | ||||||
<$32,000 | 133 | 15.4 | 665 | 23.2 | 718 | 24.8 |
$32,000–50,000 | 575 | 66.0 | 1909 | 62.8 | 1818 | 58.1 |
>$50,000 | 163 | 18.6 | 444 | 14.0 | 437 | 17.1 |
Median | 39637 | 38380 | 38337 | |||
Median household income2 | ||||||
<$50,000 | 176 | 18.8 | 736 | 24.2 | 691 | 22.8 |
$50,000–75,000 | 558 | 67.6 | 1870 | 63.1 | 1838 | 61.9 |
>$75,000 | 137 | 13.6 | 412 | 12.7 | 444 | 15.3 |
Median | 57755 | 56931 | 57745 | |||
% living in poverty | ||||||
<10 | 214 | 32.6 | 619 | 30.0 | 626 | 36.5 |
10–19 | 409 | 55.5 | 1165 | 54.4 | 1037 | 52.9 |
≥20 | 99 | 11.9 | 387 | 15.6 | 299 | 10.7 |
Median | 12.8 | 12.7 | 11.9 | |||
% less than high school | ||||||
<10 | 378 | 37.3 | 1471 | 43.3 | 1614 | 48.7 |
10–19 | 377 | 45.9 | 1155 | 39.8 | 1042 | 36.4 |
≥20 | 116 | 16.8 | 392 | 16.9 | 317 | 14.8 |
Median | 12.1 | 11.4 | 10.2 | |||
Unemployment rate (%) | ||||||
<5 | 273 | 30.6 | 976 | 32.6 | 1090 | 36.5 |
5–9 | 437 | 45.7 | 1550 | 43.1 | 1499 | 45.2 |
≥10 | 161 | 23.7 | 492 | 24.3 | 384 | 18.3 |
Median | 5.8 | 5.7 | 5.3 | |||
Total physicians per 100,000 | ||||||
<200 | 209 | 26.7 | 793 | 30.6 | 801 | 28.4 |
200–400 | 473 | 52.3 | 1560 | 48.4 | 1440 | 48.6 |
≥400 | 189 | 21.0 | 665 | 21.0 | 732 | 23.0 |
Median | 268.2 | 268.3 | 268.4 | |||
Total gastroenterologists per 100,0003 | ||||||
<3 | 201 | 30.3 | 625 | 32.0 | 581 | 32.0 |
3–5 | 310 | 41.7 | 957 | 42.6 | 845 | 38.1 |
>5 | 211 | 28.0 | 589 | 25.5 | 536 | 29.9 |
Median | 3.9 | 3.7 | 3.7 |
1Proportions weighted by sampling fraction.
2Adjusted to 2010 dollars.
3Poverty and total number of gastroenterologists not collected in 1990/91.
The proportion of patients who received chemotherapy differed by age at diagnosis (Table
Receipt of chemotherapy and radiation therapy among 6,862 patients diagnosed with stages II and III colorectal cancer, 1990–2010, by age and stage at diagnosis.
Stage II ( | Stage III ( | |||||
---|---|---|---|---|---|---|
Age < 50 | Age 50–69 | Age ≥ 70 | Age < 50 | Age 50–69 | Age ≥ 70 | |
| | | | | | |
Received chemotherapy1 | ||||||
Colon cancer | ||||||
No | 71 (29.2) | 465 (57.4) | 809 (86.0) | 43 (18.0) | 156 (17.9) | 439 (50.9) |
Yes | 121 (70.8) | 281 (42.6) | 131 (14.0) | 180 (82.0) | 621 (82.1) | 390 (49.1) |
Rectal cancer | ||||||
No | 28 (17.6) | 216 (34.3) | 323 (52.3) | 24 (6.0) | 101 (9.1) | 264 (42.3) |
Yes | 128 (82.4) | 444 (65.7) | 225 (47.7) | 248 (94.0) | 674 (90.9) | 307 (57.7) |
Received radiation therapy2 | ||||||
Rectal cancer | ||||||
No | 45 (28.5) | 241 (39.0) | 342 (57.1) | 67 (23.3) | 253 (30.1) | 357 (57.8) |
Yes | 112 (71.5) | 431 (61.0) | 214 (42.9) | 209 (76.7) | 531 (69.9) | 227 (42.2) |
wt.: weighted.
1Receipt of chemotherapy includes both neoadjuvant and adjuvant (or both) chemotherapy.
2Receipt of radiation therapy includes postoperative and preoperative radiation.
Our results provide a comprehensive assessment of characteristics of young-onset CRC patients across diverse settings and populations. Using a population-based sample, we found important differences in the distribution of young-onset CRC by race/ethnicity. Younger CRC patients were considerably more likely to be black or Hispanic. Moreover, these racial differences were consistent by tumor subsite, histology, and receipt of care.
There were notable racial differences in the subsite-specific distribution of young-onset CRC. Right-sided tumors predominated (39%) in younger black patients, while young white (41%) and Hispanic (33%) patients had a higher proportion of tumors located within the rectum. Young black patients also more frequently had mucinous histology, which is often associated with right-sided colon cancers. Considerable evidence suggests there are distinct CRC subtypes [
We also observed suboptimal receipt of MSI testing, as well as differences in receipt by race/ethnicity. Treatment guidelines recommend that younger (age < 50) CRC patients undergo MSI testing [
Separately, we found that a higher proportion of younger CRC patients (both stages II and III) received “optimal” treatment, including better nodal counts from surgery, treatment at academic medical centers, enrollment in clinical trials, chemotherapy, and radiation therapy, compared to the two older groups of patients. Even in the setting of stage II colon cancer, where the absolute benefit of chemotherapy is very small, the majority of younger patients (71%) received adjuvant therapy. This may reflect physician and patient treatment preferences or advances in available therapies [
An important strength of our study is the population-based sample. Data from POC studies offer a number of unique advantages for conducting population-based epidemiologic research because each participating registry area has a defined population. The age and sex distributions of patients in POC reflect those of the US population, and the SEER program includes registries with a high percentage of African Americans (Detroit, Atlanta, and Louisiana) and Hispanics (Los Angeles, Greater California, and New Mexico). POC data also provide a greater breadth and depth of information than that available solely from medical claims and/or SEER registries; detailed tumor and treatment information is abstracted from patient medical records and verified by treating physicians. This was particularly true for our assessment of receipt of chemotherapy and radiation therapy, where doctor verification substantially improved the completeness of treatment ascertainment.
The large size and diversity of this study population were also strengths that enabled us to examine CRC characteristics within population subgroups by race/ethnicity. We found that a higher proportion of Hispanic patients were diagnosed at younger ages than whites. Due to a variety of concerns, including misclassification and cultural or other differences among Hispanic and Latino groups, there has historically been limited information on cancer trends in Hispanic populations [
Our study population was limited to stages II and III patients. There may be different characteristics of younger CRC patients when considering early-stage or metastatic disease. For example, we observed only slight differences in county-level socioeconomic indicators among younger and older patients, but a relationship between CRC and socioeconomic status has been demonstrated most consistently in late-stage disease [
In summary, our study provides compelling evidence that characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity. These differences may reflect racial differences in CRC risk factors rather than disparities in diagnosis and treatment. Although exact mechanisms remain unknown, higher incidence of CRC among young black and Hispanic populations may be due to differential exposure to lifestyle-related risk factors, such as dietary patterns and a higher prevalence of obesity and sedentary behavior. Understanding differences in these risk factors by age and race/ethnicity may better elucidate reasons for the recent increase in CRC incidence in younger populations.
Dr. Sanoff received research funding through Bayer and Novartis and Dr. Lund received a Research Starter Award from the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation.
The authors declare that they have no competing interests regarding the publication of this paper.
This study was supported by the National Institutes of Health Grants T32DK07643, K07CA160772 (Hanna K. Sanoff), and K12CA120780 (Jennifer L. Lund).