Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Selection
- Confirmed genetic diagnosis of LS due to MLH1: c.1528C>T PV;
- Availability of a blood DNA sample with good quality and quantity according to the minimum requirements of the Multiplex PCR and MassArray genotyping assays (i.e., intact DNA with a concentration of >10 ng/µL and a 260/280 ratio of >1.7) [57].
2.2. Demographic and Pathological Data
2.3. DNA Samples
2.4. DNA Quality and Integrity Assessment
2.5. Sources of Studied Polymorphisms
2.6. Multiplex PCR
2.7. MassArray Genotyping
2.8. Statistical Analysis
3. Results
3.1. Patient Cohort and Demographics
3.2. Single Nucleotide Polymorphisms Genotype Frequency Distribution and Hardy–Weinberg Equilibrium Analysis
3.3. Evaluation of the Impact of Polymorphism Genotypes on the Age at First Any-Cancer Diagnosis
- i.
- Identified risk genotypes for age at first any cancer diagnosis.
- ii.
- Identified protective genotypes for age at first any-cancer diagnosis.
3.4. Evaluation of the Impact of Polymorphism Genotype on the Age at First CRC Diagnosis
- i.
- Identified risk genotypes for age at CRC diagnosis.
- ii.
- Identified protective genotypes for age at CRC diagnosis.
3.5. Aggregated Effect of Combined Risk Genotypes
3.6. Aggregated Effect of Combined Protective Genotypes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Character | N (%) N = 359 | Male (176) | Female (183) | p-Value |
---|---|---|---|---|
Status | ||||
Cancer unaffected | 189 | 84 (47.7%) | 105 (57.4%) | 0.085 |
Cancer affected | 170 | 92 (52.3%) | 78 (42.6%) | |
Cancer-Affected | ||||
Age at cancer diagnosis | ||||
Mean (SD) | 170 | 41.8 (10.9) | 45.5 (10.6) | 0.028 |
Median [Min, Max] | 170 | 40.5 [19.9, 68.8] | 46.6 [17.0, 73.6] | |
Cancer type | ||||
CRC | 136 | 86 (93.5%) | 50 (64.1%) | <0.001 |
Extra-colonic 1 | 34 | 6 (6.5%) | 28 (35.9%) | |
CRC histological grade | ||||
Poorly differentiated | 23 | 20 (23.3%) | 3 (6.0%) | 0.009 |
Moderately differentiated | 113 | 66 (76.7%) | 47 (94.0%) | |
CRC histological type | ||||
Adenocarcinoma | 116 | 70 (81.4%) | 46 (92.0%) | 0.132 |
Mucinous adenocarcinoma | 20 | 16 (18.6%) | 4 (8.0%) | |
Cancer recurrence | ||||
Yes | 36 | 15 (16.3%) | 21 (26.9%) | 0.134 |
No | 134 | 77 (83.7%) | 57 (73.1%) |
Number of Genotypes | Unadjusted HR (95% CI) | p-Value | # p-Value | * Adjusted HR (95% CI) | p-Value | # p-Value |
---|---|---|---|---|---|---|
No cancer risk genotype | Ref | Ref | ||||
One to Two any cancer risk genotypes | 1.44 (1.03–2.00) | 0.031 | 0.050 | 1.49 (1.06–2.09) | 0.020 | 0.030 |
Number of Genotypes | Unadjusted HR (95% CI) | p-Value | # p-Value | * Adjusted HR (95% CI) | p-Value | # p-Value |
---|---|---|---|---|---|---|
No cancer risk genotype | Ref | Ref | ||||
One to two any cancer protective genotypes | 0.49 (0.35–0.69) | <0.001 | <0.001 | 0.52 (0.37–0.73) | <0.001 | <0.001 |
One to two CRC protective genotypes | 0.50 (0.34–0.72) | <0.001 | <0.001 | 0.51 (0.36–0.74) | <0.001 | <0.001 |
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Ndou, L.; Chambuso, R.; Algar, U.; Goldberg, P.; Boutall, A.; Ramesar, R. Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant. Biomedicines 2024, 12, 2201. https://doi.org/10.3390/biomedicines12102201
Ndou L, Chambuso R, Algar U, Goldberg P, Boutall A, Ramesar R. Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant. Biomedicines. 2024; 12(10):2201. https://doi.org/10.3390/biomedicines12102201
Chicago/Turabian StyleNdou, Lutricia, Ramadhani Chambuso, Ursula Algar, Paul Goldberg, Adam Boutall, and Raj Ramesar. 2024. "Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant" Biomedicines 12, no. 10: 2201. https://doi.org/10.3390/biomedicines12102201
APA StyleNdou, L., Chambuso, R., Algar, U., Goldberg, P., Boutall, A., & Ramesar, R. (2024). Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant. Biomedicines, 12(10), 2201. https://doi.org/10.3390/biomedicines12102201