The etiology of pancreatic cancer remains a topic of ongoing research, with current consensus suggesting a multifactorial influence spanning environmental, hereditary, demographic, lifestyle, genetic, and psychosocial factors. Environmental elements, particularly lifestyle choices such as smoking, exposure to secondhand smoke, and excessive alcohol consumption, are notably impactful in the incidence and progression of pancreatic cancer.

Moreover, psychological and demographic factors are acknowledged to modulate the risk of pancreatic cancer. The varying susceptibility within populations, despite similar environmental risk exposures, underscores the significance of genetic predisposition in the disease’s onset and progression. The role of genetic factors, especially at the single nucleotide polymorphism (SNP) level, is increasingly recognized in the pathogenesis of pancreatic cancer. Susceptibility genes of interest primarily include oncogenes, tumor suppressor genes, and DNA repair genes, with their polymorphisms accounting for individual variations in disease response and progression due to environmental factors.

XRCC3, a crucial DNA repair gene, functions as a molecular scaffold, facilitating single-strand break repair and base excision repair by binding to repair-related proteins. Epidemiological data increasingly suggest a link between repair gene polymorphisms and cancer risk, with XRCC3 implicated in various malignancies, including lymphoma, lung, esophageal, salivary gland, colorectal, cervical, breast, and stomach cancers [21,22,23,24,25,26,27,28]. Our findings indicate a decreased risk in Caucasian populations, marking this as potentially the first meta-analysis to focus on this aspect. However, the current results indicate that XRCC3 Thr241Met polymorphism is not associated with the risk of pancreatic cancer in Hispanics population or African population. We think the different results from different population are not surprising, because the results of genetic polymorphism are influenced by many aspects such as geography, ethnicity and environment. And even within the same continent or within the same country, there can still be racial differences. China, Iran, India, Saudi Arabia and other countries are all in Asia, but there are obvious differences in their race. Furthermore, even if different studies study the same race, they may get different results due to the difference in sample size, which is also the reason for our meta-analysis. By conducting Between-Study Heterogeneity and meta-regression, we successfully identified the source of heterogeneity and reduced the impact of heterogeneity to a very low level through subgroup analysis, thus ensuring the reliability of the meta-analysis results. Finally, the sensitivity analysis and publication bias also show that our results are very convincing.

However, several limitations warrant consideration. Primarily, the inclusion of more diverse studies, particularly from Asian, African, and other ethnic groups, would enhance the meta-analysis. Additionally, the influence of various confounders could not be fully assessed due to insufficient data, and the overall participant number in our study is relatively small.

In summary, our findings suggest that the XRCC3 Thr241Met polymorphism is associated with a reduced risk of pancreatic cancer in Caucasian populations. Further research is imperative to corroborate these findings.

All data generated or analyzed during this study are included in this published article.