Colorectal cancer in young adults

Colorectal cancer rates rising dramatically in young adults

Colorectal cancer risk for millennials has escalated back to the level of those born in the late 1800s

Adults born in 1990 are twice as likely to be diagnosed with colon cancer and four times as likely to be diagnosed with rectal cancer as people born in 1950.

Three in 10 rectal cancer diagnoses are now made in patients aged younger than 55 years.

Early onset colorectal cancer <50 years) now accounts were approximately 10% of all new diagnoses of this cancer, and an accompanying increasing colorectal cancer related mortality has been observed among younger patients.

This trend is in contrast to the steady decline in the incidence of later on so colorectal cancer and related mortality over the past two decades in the US.

Some of the factors known to increase CRC risk include:  excess body weight; sedentary behavior; high consumption of red/processed meat; and low consumption of fruits, vegetables, Western diet, smoking, consumption of sugar sweetened beverages, and dairy products with calcium have probably contributed to the increase.

Other potential risk factors for the increase in incidence in CRC in younger individuals includes reduced physical activity, reduced use of aspirin and other nonsteroidal anti-inflammatory drugs, and dietary changes.

Obesity is significantly associated with early onset colorectal cancer, but not in all studies.

Prevalence of metabolic syndrome has increased among young adults and is associated with early onset colorectal cancer.

Firefighters may be at higher risk for colorectal cancer due to their exposures.

These include toxic chemicals produced during fires and, in particular, asbestos fibers which firefighters encounter at most structural fires since asbestos was the dominant thermal insulation and fire prevention material in use for decades.

Since the mid-1980s, CRC incidence rates rose 2.4% annually among adults aged 20 to 29 years and 1% annually in adults aged 30 to 39 years. 

From the mid-1990s, rates increased 1.3% annually among adults aged 40 to 49 years and 0.5% annually among adults aged 50 to 54 years.

The rise in incidence in younger adults appeared steeper for rectal than colon cancer.

Rectal cancer rates increased 3.2% annually from 1974 to 2013 in adults aged 20 to 29 years, 3.2% annually since 1980 in adults aged 30 to 39 years, and 2.3% annually since 1990 in adults aged 40 to 49 years and 50 to 54 years. 

Rectal cancer rates dropped over the entire 40-year study period for adults aged 55 years and older.

The proportion of diagnoses in adults aged younger than 55 years doubled from 14.6% to 29.2% for rectal cancer and increased from 11.6% to 16.6% for colon cancer.

Age-specific risk by birth show that those born in 1990 have double the risk for colon cancer and four times the risk for rectal cancer than those born in 1950.

Adults with a family history of CRC or a mother, father or sibling who has had a polyp, should begin screening by age 40 years.

The prevalence of a mutation in a high penetrants cancer susceptibility gene is relatively high among patients younger than 50 years of age, at 16 to 25%, which is nearly double the prevalence in unselected patients with colorectal cancer.

Mutations in MMR, APC, MUTYH, BNP1A, SMAD4, PTEN, and STK11 have elevated risk of cancer in carriers.

Molecular alterations in microsatellite stable cancers are similar across age groups except that APC, KRAS, and BRAF mutations are significantly more common in patients 50 years of age or older.

Alterations in TP53 and CTNNB one or more common in patients younger than 40 years of age.

Cancer risk is influenced polygenic effects.

Colorectal cancer (CRC) incidence rates in the United States overall have declined since the mid-1980s because of changing patterns in risk factors and increases in screening.  however, this progress is increasingly confined to older adults. 

CRC occurrence has been on the rise in patients younger than age 50, often referred to as early-onset disease, since the mid-1990s. 

Young patients are more often diagnosed at an advanced stage and with rectal disease than their older counterparts.

Patients with young onset colorectal cancer are associated with more aggressive disease biology and significantly more likely to present with stage III or IV and more left-sided tumors compared with patients with average age onset of colorectal cancer.

Young patients are less likely to have a usual source of health care; often need a more complex treatment protocol to preserve fertility and sexual function; are at higher risk of long-term and late effects, including subsequent primary malignancies; and more often suffer medical financial hardship. 

Early onset colorectal cancers are more likely detected in the rectum, followed by the distal colon: more than 70% of early onset colorectal cancer are in the left colon at presentation.

In later onset colorectal cancer‘s there a similar frequencies of onset in the proximal and distal colorectum.

Early onset colorectal cancers are more likely than later onset cancers to display MSI – H which is strongly associated with poor tumor differentiation.

The frequency of MSI-H in young adult patients with colorectal cancer is approximately 17%.

Diagnosis is often delayed because of the need for a high index of suspicion if young patients present with rectal bleeding or changes in bowel habits. 

The rate of early-onset CRC, < 50 years at diagnosis, has been increasing for 2 decades for unknown reasons.

Screening for CRC in average-risk patients is recommended by the American Cancer Society to begin at age 45.

Younger patients present with characteristic symptoms of abdominal pain, rectal bleeding, and changes in bowel habits, but diagnosis often is delayed.

Patients with early-onset CRC are treated in the adjuvant and metastatic setting, just as their older counterparts are.

The incidence patterns in young patients with CRC are consistent in men and women, implicating exposures that are not sex-specific but vary by anatomic subsite, stage at diagnosis, race and ethnicity, and geographic area of residence. 

Inclines are steepest for advanced-stage disease, for tumors in the distal colon and rectum.

The unique increase among young people is also occurring outside the United States in many high-income countries.

The  median age at CRC diagnosis has decreased from age 72 in the early 2000s to age 66 today.

Major established modifiable risk factors for CRC are excess body weight, cigarette smoking, heavy alcohol consumption, a high intake of red or processed meat, and physical inactivity.

These associations are based almost entirely on cancer occurrence in older individuals.

A recent retrospective study of patients diagnosed at a New York academic center found no significant associations between obesity, smoking, and diabetes and early onset colorectal cancer (EO-CRC risk).

A history of antibiotic use among individuals younger than 50 appears to increase the risk of developing colon cancer but not rectal cancer by 49%.

Antibiotics substantially alter the gut microbiome and prolonged use may be a risk factor for early onset colorectal cancer.

The risk of early onset colorectal cancer among U.S. women was recently shown to have increased by 20% for every 5-unit increase in body mass index and by 69% for more than 14 hours per week of television watching.

Associations have been reported between colorectal tumors and antibiotic use as well as high-fructose corn syrup, suggesting alterations in the composition of gut microbiota.

The strongest known risk factor for CRC is a family history of the disease. 

Nearly 30% of patients with early onset colorectal cancer have a family history of this cancer and at least one first degree relative.

A 3 to 5% overall prevalence of hereditary colorectal cancers in population studies, of which the Lynch syndrome is the most common.

Patients with a first-degree relative who has been diagnosed with CRC have two to four times the risk of someone without this family history.

Patients with a first degree relative with CRC have a higher risk for diagnosis before age 50.

CRC history among more distant relatives is also associated with increased risk in younger adults.

Similar higher risk occurs in a family with a history of adenomas.

More than one-quarter of patients younger than age 50 have a first degree relative with a history of CRC or adenomas, and an additional 16% have a hereditary syndrome, half of whom have Lynch syndrome.

Most of the estimated 1.2 million Americans (1 in 279) who have Lynch syndrome are undiagnosed.

It is recommend universal testing for Lynch syndrome in patients with CRC or endometrial cancer.

A larger proportion of early CRCs are hereditary compared with late CRCs, the majority of cases are sporadic.

CRC is the most commonly diagnosed cancer and the leading cause of cancer death in men younger than age 50, whereas in women it ranks fourth (after breast, thyroid, and melanoma) and second (after breast) in terms of incidence and mortality, 

Although the absolute risk of a CRC diagnosis by age 50 remains low  at 0.4% vs. 3.3% from age 50 to 85, the burden for young adults is substantial and growing.

In 2020, 17,930 (12%) of the estimated 147,950 cases of CRC in the United States will be diagnosed in people younger than age 50

Approximately 50 per day are diagnosed at age 50 or below withnCRC.

In addition to 3,640 of 53,200 CRC deaths occur in that age group.

The majority of people diagnosed with CRC before age 50 are at average risk with respect to screening,  and half (48%) of these patients are age 45 to 49.

Sudies support screening before age 50. 

Average-risk adults age 40 to 49 appear to have prevalences of any adenoma (14%–16%), large polyps (3%–4% in women and in 5%–6% men), and distal large polyps (5%) similar to those observed among adults age 50 to 54.

Screening before age 50 is universally recommended for people at elevated risk of CRC because of familial syndromes: familial adenomatous polyposis, Lynch syndrome, chronic inflammatory bowel disease, or a family history of CRC or adenoma.

In recent years the incidence rates among non-Hispanic whites age 20 to 49 are the same as those among blacks (14.1 per 100,000).

There has been a marked increase in early onset colorectal cancer among white persons, and the elevated levels for black individuals has been relatively stable.

Young patients are diagnosed at a later stage than older patients, even when screening-detected cancers are excluded.66

The biggest increases in CRC are occurring among people younger than age 40, suggesting  that consideration should be given to starting screening at age 40.

A large proportion of patients with sporadic early onset CRC have a family history of advanced polyps.

It is recommended to have screening for patients who have first degree relative with an advanced adenoma before age 60, at age 40.

Early screening is those who have received pelvic radiation in adolescence or early adulthood. 

There is predominance of left-sided or rectal cancers in early onset CRC: sigmoidoscopy screening initiated at an earlier age could be another screening solution.

A single-institution study found a median time from onset of rectal cancer symptom to treatment of 217 days for patients younger than age 50 compared with 29.5 days for those older than age 50, largely because of patient delays in presentation to the initial physician.

Some of the delay  is caused by misdiagnosis.

Among the 52% of patients with early onset CRC who experienced rectal bleeding, the average time from onset of bleeding to diagnosis was 271.17 days.

The American Society for Gastrointestinal Endoscopy recommends endoscopic evaluation of all patients with lower gastrointestinal bleeding.

Compared with older patients, patients with early onset CRC have higher cancer-specific survival at every stage, despite usually high-risk pathology, as indicated by population-based studies: reflect fewer comorbidities or more aggressive treatment regimens. 

However, patients with early onset colorectal cancer tend to present with advanced stage disease, which is associated with increased mortality: data suggests that worst outcomes for patients with early onset colorectal cancer appear to be primarily due to more advanced disease at diagnosis.

In the metastatic setting, patients with early onset CRC treated with standard regimens or clinical trials can have poorer progression-free survival but do not have worse overall survival or response rates.

Patients with early onset CRC are more likely to receive additional surgical therapy for both early-stage and metastatic disease, reflecting both patient and provider age-related biases.

Current national and international guidelines do not have different treatment recommendations for patients with early onset CRC.

A more aggressive treatment program  is often pursued, leading  to potential overtreatment with unclear benefits.

More patients with early-stage early onset CRC (age 18–49) are given adjuvant therapy for stage II and III disease, including low- and high-risk stage II disease: however no survival advantage is noted.

The efficacy of specific systemic agents based on age, shows no differences.

Treatment recommendations for metastatic disease are the same regardless of age. 

The most common cause of death for early onset CRC  survivors is the same as for any other person of that age.

Secondary cancers become a more common cause of death and the eventual leading cause of death 11 to 15 years after treatment. 

The unique clinical challenges for patients with early onset CRC: Diagnostic delays, financial toxicity, sexual and fertility considerations, and long-term survivorship concerns. 

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