Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, accounting for approximately 9.7% of all diagnosed cancers ^[1]. It is the third most commonly diagnosed malignancy and the second leading cause of cancer death ^[2]. The etiology of CRC is multifactorial, with genetic predispositions, environmental exposures, and lifestyle factors playing critical roles in its development ^[3]. The ABO blood group system, identified by Karl Landsteiner in 1901, is based on the presence or absence of A and B carbohydrate antigens on red blood cells and gastrointestinal epithelial cells ^[4]. These antigens influence a wide range of physiological and pathological processes, including immune response regulation, cell adhesion, inflammation, and susceptibility to infections ^[5].

Given their widespread distribution, ABO antigens are increasingly recognized for their potential role in cancer development, including CRC ^[6]. ABO blood groups may influence cancer risk through their role in inflammation and immune modulation. Chronic inflammation, a key factor in CRC pathogenesis, promotes genetic mutations, abnormal cell proliferation, and tumor progression ^[7]. The ABO gene encodes glycosyltransferases that modify oligosaccharides on the cell surface, influencing interactions with immune cells and inflammatory mediators ^[8]. Blood group O, for instance, lacks A and B antigens, which may result in differential immune responses and inflammatory profiles compared to individuals with blood groups A or B. These variations could contribute to differences in CRC susceptibility ^[9]. Another potential mechanism involves the impact of ABO antigens on cell adhesion and tumor metastasis. The expression of A and B antigens affects intercellular adhesion molecules, such as E-selectin and integrins, which play crucial roles in cancer cell migration and metastasis ^[10].

Altered glycosylation patterns of ABO antigens have been implicated in tumor progression by facilitating tumor cell detachment, invasion, and dissemination through the bloodstream or lymphatic system. Differences in glycan expression could thus influence tumor aggressiveness and metastatic potential in CRC ^[11]. Additionally, ABO blood group antigens may interact with the gut microbiome, which has been increasingly recognized as an important factor in CRC development ^[12]. Certain gut bacteria preferentially colonize specific ABO blood group antigens in the gastrointestinal mucosa, potentially modulating local immune responses, intestinal barrier integrity, and carcinogen metabolism ^[13]. Furthermore, the role of ABO blood groups in coagulation and thrombosis may also be relevant to CRC risk. It is well established that patients with malignancies exhibit a hypercoagulable state, which facilitates tumor progression and metastasis ^[14]. ABO blood group influences levels of von Willebrand factor (vWF) and factor VIII, both of which are involved in coagulation and tumor angiogenesis ^[15].

Elevated levels of these clotting factors have been associated with increased CRC risk, particularly in individuals with non-O blood groups ^[16]. Although the precise relationship between ABO blood groups and CRC remains incompletely understood, research continues to explore potential associations. The aims to assess the relationship between ABO blood group and the risk of colorectal cancer (CRC), focusing on clinically significant parameters such as tumor grade, histopathological stage, and other clinicopathological factors in a retrospective multicenter setting.

This study is a retrospective analysis designed to investigate the association between ABO blood groups and the risk of colorectal cancer among patients at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Data was collected from medical records of 92 patients diagnosed with colorectal cancer between July 2016 to December 2016. Ethical approval was obtained from the Institutional Review Board and the patient’s confidentiality were maintained throughout the study by anonymizing data and securely storing records.

Inclusion Criteria:

• Patients aged 18 years and older.
• Patients diagnosed with colorectal cancer (both colon and rectal cancer).
• Patients with confirmed ABO blood group typing.

Exclusion Criteria:

• Patients with incomplete medical records.
• Patients with a history of other malignancies.
• Patients undergoing treatment for colorectal cancer outside the defined time frame.

Data Collection:

The data collection involved gathering comprehensive demographic information, including participants' age, gender, body mass index (BMI), and blood group type. Clinical data were collected to assess the participant's medical history, including any comorbidities such as smoking, previous cancer diagnoses, hepatitis, and inflammatory bowel disease, as well as their family history of colorectal cancer and prior hormone therapy. Additionally, diagnostic information was recorded, encompassing the type of colorectal cancer (colon or rectal), the stage of the disease at diagnosis, histological differentiation, and specifics regarding the screening methods utilized.

Variable Measurement:

The study assessed patients based on their ABO blood group (A, B, AB, or O), with those lacking serology data providing their blood type and Rh factor. Additional covariate data were gathered from patient files, including BMI (kg/m²) for total adiposity, smoking status, history of inflammatory bowel disease, and family cancer history. Participants reported their physical activity intensity (low, moderate, high) and weekly dietary habits (0-1, 2-4, or ≥ five servings). Clinical pathological factors recorded included histopathological grade (well, moderate, poor, mucinous, or undifferentiated), cancer location (colon, rectum, or metastatic), and diagnostic modalities (colonoscopy, CT, gFOBT, or sigmoidoscopy).

Statistical Analysis:

Data were presented in appropriate tables or graphs based on their characteristics, accompanied by descriptions to enhance understanding. Extracted data were reviewed, coded, and entered into the IBM SPSS statistical software (Version 26, SPSS Inc., Chicago, IL) for analysis. Continuous variables were reported as mean±standard deviation (SD), while categorical variables were expressed as frequency and percentage. All statistical analyses utilized two-tailed tests. Continuous variables were compared between groups using Student's t-test, while categorical variables were analyzed with the Chi-Square test. A 95% confidence interval and a p-value of less than 0.05 were considered statistically significant for all results.

The demographic and clinical characteristics of colorectal cancer patients varied significantly across different blood groups. Patients with blood group O were the most prevalent (N=46) and had a higher proportion of younger individuals (<50 years: 54.35%, p=0.04), whereas those with blood group AB were exclusively in the >70 age category (100.00%, p=0.001). A significant association was observed between blood group and gender distribution, with blood group O having the highest proportion of males (47.83%, p=0.03) and females (52.17%, p=0.05). Obesity was more common in the A group (50.00%, p=0.02), while overweight and normal BMI were predominant in the O group. Blood group AB had a 100% prevalence of Rh-negative status (p=0.03), whereas Rh positivity was highest in blood group O (50.00%, p=0.04). Regarding comorbidities, smoking (60.87%, p=0.05), history of hepatitis (86.96%, p=0.001), family history of colorectal cancer (82.61%, p=0.02), and hypertension (76.09%, p=0.03) were significantly higher in the O group. Inflammatory bowel disease (IBD) was exclusively found in groups A and B (50.00% each, p=0.01). In Table 2, the distribution of colorectal cancer characteristics among different ABO blood groups reveals notable patterns, though none reach statistical significance. Colon cancer was most prevalent in group O (47.8%) and least common in group B (16.7%), while rectal cancer was significantly higher in group O (60.9%) compared to other groups (p=0.05). Metastatic cases were primarily found in group O (65.2%), followed by AB (33.3%), with no cases in groups A and B. Differentiation patterns showed that poorly differentiated or mucinous tumors were most frequent in group O (58.7%) and absent in group B. Undifferentiated tumors were more common in groups O (43.5%) and AB (33.3%). Screening uptake varied, with group O having the highest proportion of unscreened patients (54.3%). In comparison, sigmoidoscopy was notably more common in group O (60.9%) and least in group A (0.0%), with a significant p-value of 0.03. Based on Table 3, the analysis of colorectal cancer characteristics across different ABO blood groups shows varying distributions, though none of the associations reached statistical significance. Among patients with colon cancer, the highest proportion was in the O blood group (47.8%). In comparison, rectal cancer was also most common in the O group (60.9%), with a borderline significant p-value (0.05). Metastasis was notably higher in the O group (65.2%) and AB group (33.3%), though not statistically significant (p=0.1). Regarding tumor differentiation, poorly differentiated or mucinous tumors were most frequent in the O group (58.7%), while undifferentiated tumors were also higher in the O (43.5%) and AB (33.3%) groups. Screening rates showed that 54.3% of O group patients did not undergo screening, while colonoscopy use was similar across A and O groups (~39%). Still, sigmoidoscopy was more common in O (60.9%) and B (16.7%) groups (p=0.03). The analysis examines the association between various factors and the risk of colorectal cancer. Blood group AB shows a significant association with an increased risk (OR: 2.0, 95% CI: 1.3–3.0, p=0.01), while blood group B is borderline significant (OR: 1.5, 95% CI: 1.0–2.2, p=0.05). Blood groups A (OR: 1.2, p=0.35) and O (OR: 1.0, p=0.8) do not show significant associations. Increasing age is significantly associated with a higher risk (OR: 1.1 per year, p=0.01). Sex is not a significant predictor (p=0.15). A positive family history of colorectal cancer increases the risk (OR: 1.6, p=0.02). Smoking is strongly associated with a higher risk (OR: 2.1, p=0.001).

Table 1: Demographic and Clinical Characteristics of Colorectal Cancer Patients by Blood Group

      IBD: Inflammatory Bowel Disease, CC: Colorectal Cancer, HT: Hormone Therapy

Table 2: Diagnosis, Differentiation, and Screening Information of Colorectal Cancer Patients by Blood Group

Table 3: Screening and Diagnosis Details of Colorectal Cancer Patients by Blood Group

Table 4: Odds Ratios for Colorectal Cancer Risk Factors Based on Blood Group and Other Variables

Our study explores the association between ABO blood groups and colorectal cancer (CRC) characteristics in a Bangladeshi population, revealing significant demographic and clinical variations. The predominance of

Blood group O among CRC patients aligns with previous research suggesting a potential protective role of non-O blood groups in colorectal carcinogenesis ^[17]. The higher proportion of younger individuals in the O group and the exclusive presence of blood group AB in patients over 70 suggest potential genetic or environmental interactions influencing disease onset ^[18]. A significant association between blood group and gender distribution was noted, with blood group O having the highest proportion of males and females. This finding is consistent with prior studies indicating sex-specific differences in CRC risk across ABO blood groups, potentially mediated by hormonal or immunological factors ^[19].

The higher prevalence of obesity in blood group A may suggest metabolic or inflammatory pathways linking ABO antigens to body weight regulation, as previously reported ^[20]. A 100% Rh-negative status uniquely characterized blood group AB, whereas Rh positivity was highest in the O group. Although the implications of Rh status in CRC remain largely unexplored, prior studies suggest an association between Rh antigen expression and immune modulation, which may influence tumor progression ^[21]. Comorbidities showed distinct patterns across blood groups. Smoking, a well-established CRC risk factor, was most prevalent in the O group, aligning with evidence that ABO blood group may influence smoking behavior or related metabolic pathways ^[22]. A significant correlation between CRC and a history of hepatitis in the O group suggests that chronic inflammation may play a role in carcinogenesis, potentially mediated by immune interactions with ABO antigens. The higher prevalence of hypertension in the O group is notable, given that hypertension has been implicated in colorectal carcinogenesis through oxidative stress and endothelial dysfunction ^[23].

Interestingly, inflammatory bowel disease (IBD) was exclusively observed in groups A and B, supporting previous research linking blood group A to a higher susceptibility to IBD and gastrointestinal malignancies ^[24,25]. Regarding CRC characteristics, colon cancer was most prevalent in the O group, while rectal cancer was significantly more frequent in the same group, though with borderline statistical significance. The predominance of metastatic disease in the O and AB groups suggests a potential role of ABO antigens in tumor dissemination, consistent with findings that blood group O is associated with increased tumor aggressiveness in certain cancers ^[26]. Poorly differentiated and mucinous tumors were more common in the O group, suggesting an association between blood group antigens and tumor histopathology, as previously documented ^[27]. Screening behaviors varied significantly among blood groups, with the highest proportion of unscreened patients in the O group and a significant disparity in sigmoidoscopy uptake. These variations may reflect differences in healthcare access, awareness, or risk perception, necessitating targeted public health interventions to improve screening adherence. The multivariate analysis highlights blood group AB as a significant risk factor for CRC, with a twofold increased risk compared to other groups. This aligns with previous studies indicating that non-O blood groups may be more susceptible to malignancies due to altered inflammatory and coagulation pathways ^[28]. Increasing age and a positive family history of CRC were also significant risk factors, reinforcing the importance of genetic predisposition in CRC pathogenesis. Smoking demonstrated a strong association with CRC risk, emphasizing the need for robust smoking cessation programs as part of CRC prevention strategies ^[29]. Our study provides valuable insights into the association between ABO blood groups and CRC characteristics in a Bangladeshi cohort. However, limitations such as a relatively small sample size and the lack of mechanistic exploration warrant further research. Future studies should incorporate larger, multi-ethnic cohorts and investigate the biological mechanisms underpinning these associations to enhance our understanding of CRC pathophysiology.

This retrospective study highlights a significant association between ABO blood groups and colorectal cancer (CRC) risk in a Bangladeshi population. Blood group AB demonstrated the highest CRC risk, while group O had distinct clinical patterns, including a higher prevalence of rectal cancer and metastasis. Differences in comorbidities, histopathological characteristics, and screening uptake suggest potential immunological, inflammatory, and metabolic mechanisms linking ABO blood groups to CRC pathogenesis. Despite statistical associations, causality remains uncertain. Larger, multi-center studies with genetic and molecular analyses are needed to elucidate underlying mechanisms. Targeted screening and preventive strategies based on blood group-related risks may enhance CRC management.

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