Young-onset colorectal cancer risk among individuals with iron-deficiency anaemia and haematochezia

Abstract

ObjectiveYoung-onset colorectal cancer (YCRC) incidence is rising. Scant data exist on YCRC risk after presentation with concerning symptoms such as iron-deficiency anaemia (IDA) or haematochezia. We examined the association between IDA and YCRC, and haematochezia and YCRC.DesignCohort study of US Veterans aged 18–49 years receiving Veterans Health Administration (VHA) care 1999–2016. IDA analytic cohort was created matching individuals without incident IDA to those with IDA 4:1 based on sex, birth year and first VHA visit date (n=239 000). We used this approach to also create a distinct haematochezia analytic cohort (n=653 740). Incident YCRC was ascertained via linkage to cancer registry and/or cause-specific mortality data. We computed cumulative incidence, risk difference (RD) and HRs using Cox models in each cohort.ResultsFive-year YCRC cumulative incidence was 0.45% among individuals with IDA versus 0.05% without IDA (RD: 0.39%, 95% CI: 0.33%–0.46%), corresponding to an HR of 10.81 (95% CI: 8.15–14.33). Comparing IDA versus no IDA, RD was 0.78% for men (95% CI: 0.64%–0.92%) and 0.08% for women (95% CI: 0.03%–0.13%), and RD increased by age from 0.14% for <30 years to 0.53% for 40–49 years. YCRC cumulative incidence was 0.33% among individuals with haematochezia versus 0.03% without haematochezia (RD: 0.30%, 95% CI: 0.26%–0.33%), corresponding to an HR of 10.66 (95% CI: 8.76–12.97). Comparing haematochezia versus no haematochezia, RD increased by age from 0.04% for <30 years to 0.43% for 40–49 years.ConclusionColonoscopy should be strongly considered in adults aged <50 years with IDA or haematochezia without a clinically confirmed alternate source.

Iron deficiency and symptoms in women aged 20–49 years and relation to upper gastrointestinal and colon cancers

“… 15 Second, in 2020, a large Veterans Administration study was published examining the rate of colon cancer in those with IDA and age 18–49 years. 11 Their 5-year cumulative incidence in women aged 18–49 years was 0.11%, lower than in our study. Unlike our study, their controls were all those without IDA without requirement for iron testing nor stratifying by anaemia status, nor did they examine the role of symptoms.…”

“…A 2-year follow-up of the 1971–1974 National Health and Nutrition Examination Survey found that none of the 92 premenopausal women with IDA were diagnosed with gastrointestinal malignancy, nor were 350 ID without anaemia 15. Second, in 2020, a large Veterans Administration study was published examining the rate of colon cancer in those with IDA and age 18–49 years 11. Their 5-year cumulative incidence in women aged 18–49 years was 0.11%, lower than in our study.…”

“…[3][4][5][6][7][8][9][10] A recent Veterans Administration study was large and population based but did not examine the role of symptoms. 11 Data are even more scarce in those with iron deficiency (ID) without anaemia. 12 In order to examine the inter-relation of ID, anaemia and symptoms on the incidence of major GI cancers in women of menstruating age, we undertook a retrospective cohort study.…”

“…Most studies of the incidence of malignancy in this population are small and performed in those referred for endoscopy, with case series ranging in size from 19 to 187 women 3–10. A recent Veterans Administration study was large and population based but did not examine the role of symptoms 11. Data are even more scarce in those with iron deficiency (ID) without anaemia 12.…”

Dysbiosis of human gut microbiome in young-onset colorectal cancer

“…Young-onset CRC (yCRC) patients often present with more advanced disease and adverse pathological features compared to their older counterparts 7 . This may have a negative impact on their survival outcome 8,9 . Diagnostic and therapeutic protocols dedicated to sporadic CRC in young individuals are currently an unmet clinical need.…”