Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Thyroid cancer (TC) is a rising global health concern, with ionizing radiation and heritability as known risk factors.
• Limited understanding of genetic susceptibility to TC persists despite advances in genome-wide association studies.
• The DNA mismatch repair (MMR) system's potential role in TC pathogenesis is suggested by preliminary research.

Purpose of the Study:

• To investigate the association between specific DNA mismatch repair (MMR) gene single nucleotide polymorphisms (SNPs) and susceptibility to well-differentiated thyroid cancer (DTC).
• To evaluate the potential of MMR SNPs as biomarkers for DTC risk stratification.

Main Methods:

• A case-control study involving 106 DTC patients and 212 controls of Caucasian Portuguese descent.
• Genotyping of six MMR SNPs (MLH1, MSH3, MSH4, PMS1, MLH3, MSH6) using TaqMan® assays.
• Statistical analysis to calculate genotype-associated risk estimates, including adjusted odds ratios (OR) and confidence intervals (CI).

Main Results:

• The MSH6 rs1042821 variant homozygote genotype was associated with a significantly increased risk of DTC (OR=3.42-3.84, P=0.03-0.04).
• This increased risk was particularly notable in individuals with follicular histotype and female sex.
• Combinations of MMR SNPs, including MSH6, showed both increased risk and potential protective effects, suggesting complex gene interactions.

Conclusions:

• Specific MMR SNPs, notably MSH6 rs1042821, may contribute to individual susceptibility to well-differentiated thyroid cancer.
• The findings support the role of MMR system variations in DTC pathogenesis.
• Further research is warranted to validate these SNPs as biomarkers for personalized DTC prevention and optimized cancer policies.