Background

Sex hormones may be associated with colorectal adenocarcinoma, although the association of pregnancy history and risk of colorectal cancer is not consistent.

Methods

We conducted a population-based nested case-control study of persons born between 1932 and 2008 who are in the Swedish Multi-Generation Register. In total, 12,915 women and 15,519 men with colorectal adenocarcinoma were identified during follow-up in the Swedish Cancer Register; 10 age- and sex-matched controls were selected for each case. Number of children and age at first and last birth were analyzed in relation to the risk of colorectal adenocarcinoma, using conditional logistic regression, to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Compared with women without children, women with 1 or 2 children had an OR of 1.02 (95% CI = 0.93-1.13) of developing adenocarcinoma in the proximal colon; those with 3 or 4 children, 1.18 (1.06-1.32); and those with ≥5 children, 1.30 (1.05-1.61) (test for trend P < 0.01). The corresponding associations in men were 0.92 (0.84-1.00), 1.02 (0.92-1.13), and 0.97 (0.78-1.20), respectively (test for trend P = 0.13).

Conclusions

Higher parity in women was associated with the risk of adenocarcinoma of the proximal colon, although not the distal colon or rectum. A similar risk with family size was not seen for fathers. Still, the influence of lifestyle factors cannot be ruled out.

Background

Epidemiological studies have shown a potential association between sex hormones and colorectal cancer. The risk of colorectal cancer in breast cancer patients who may have been exposed to increased levels of endogenous sex hormones and/or exogenous sex hormones (e.g. anti-hormonal therapy) has not been thoroughly evaluated.

Methods

Using the National Swedish Cancer Register we established a population-based prospective cohort of breast cancer patients in women diagnosed in Sweden between 1961 and 2010. Subsequent colorectal cancers were identified from the same register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs) were used to estimate the risk of colorectal cancer after a diagnosis of breast cancer. The association between breast cancer therapy and risk of colorectal cancer was evaluated in a subcohort of breast cancer patients treated in Stockholm between 1977 and 2007. Hazard ratios (HRs) and 95%CIs were estimated using Cox regression models.

Results

In a cohort of 179,733 breast cancer patients in Sweden, 2571 incident cases of colorectal cancer (1008 adenocarcinomas in the proximal colon, 590 in the distal colon and 808 in the rectum) were identified during an average follow-up of 9.68 years. An increased risk of colorectal adenocarcinoma was observed in the breast cancer cohort compared with that in the general population (SIR=1.59, 95%CI: 1.53, 1.65). Adenocarcinoma in the proximal colon showed a non-significantly higher SIR (1.72, 95%CI: 1.61, 1.82) compared with the distal colon (1.46, 95%CI: 1.34, 1.58). In the subcohort of 20,171 breast cancers with available treatment data, 299 cases with colorectal cancers were identified. No treatment-dependent risk of colorectal cancer was observed among the breast cancer patients.

Conclusion

An increased risk of colorectal adenocarcinoma - especially in the proximal colon - was observed in the breast cancer cohort. Breast cancer treatment did not alter this risk.

Importance

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.

Observations

Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.

Conclusions and relevance

The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Background

Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group.

Methods

The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes.

Results

A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%).

Conclusion

A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters.

Background

The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status.

Methods

Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated.

Results

A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively).

Conclusion

Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.