Formaldehyde (FA) is a commonly used chemical in anatomy and pathology laboratories as a tissue preservative and fixative. Because of its sensitising properties, irritating effects and cancer implication, FA accounts probably for the most important chemical-exposure hazard concerning this professional group. Evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting, particularly in regard to the ability of inhaled FA to induce toxicity on other cells besides first contact tissues, such as buccal and nasal cells. To evaluate the effects of exposure to FA in human peripheral blood lymphocytes, a group of 84 anatomy pathology laboratory workers exposed occupationally to FA and 87 control subjects were tested for chromosomal aberrations (CAs) and DNA damage (comet assay). The level of exposure to FA in the workplace air was evaluated. The association between genotoxicity biomarkers and polymorphic genes of xenobiotic-metabolising and DNA repair enzymes were also assessed. The estimated mean level of FA exposure was 0.38±0.03 ppm. All cytogenetic endpoints assessed by CAs test and comet assay % tail DNA (%TDNA) were significantly higher in FA-exposed workers compared with controls. Regarding the effect of susceptibility biomarkers, results suggest that polymorphisms in CYP2E1 and GSTP1 metabolic genes, as well as, XRCC1 and PARP1 polymorphic genes involved in DNA repair pathways are associated with higher genetic damage in FA-exposed subjects. Data obtained in this study show a potential health risk situation of anatomy pathology laboratory workers exposed to FA (0.38 ppm). Implementation of security and hygiene measures may be crucial to decrease risk. The obtained information may also provide new important data to be used by health care programs and by governmental agencies responsible for occupational health and safety.

Background: Ionizing radiation exposure has been pointed out as a risk factor for thyroid cancer. The double-strand breaks induced by this carcinogen are usually repaired by homologous recombination repair pathway, a pathway that includes several polymorphic genes. Since there is a scarcity of data about the involvement of these gene polymorphisms in thyroid cancer susceptibility, we carried out a case–control study in a Caucasian Portuguese population. Methods: We genotyped 109 patients and 217 controls for the XRCC3 T241M, XRCC2 R188H, NBS1 E185Q, and RAD51 Ex1-59G>T polymorphisms to evaluate their potential main effects on risk for this pathology. Results: The results obtained showed that for the RAD51 Ex1-59G>T polymorphism, the homozigosity for the variant allele was associated with an almost significant increase of the odds ratio (OR) (adjusted OR = 1.9; confidence interval 95%: 1.0–3.5; p = 0.057). Additionaly, when the XRCC3 T241M data were analyzed concerning the presence of at least one wild-type allele, we observed that individuals homozygous for the variant allele had a higher risk for thyroid cancer (adjusted OR = 2.0; confidence interval 95%: 1.1–3.6; p = 0.026). When the data were analyzed according to the number of RAD51 Ex1-59G>T and XRCC3 T241M variant alleles, the coexistence of three or more variant alleles in either gene was associated to a significant higher risk (three variant alleles: adjusted OR = 2.9, p = 0.036; four variant alleles: adjusted OR = 8.0, p = 0.006). Conclusions: Since XRCC3 is involved in the assembly and stabilization of RAD51 protein multimers at double-strand break sites, we cannot exclude that the interaction of both polymorphisms can lead to a decreased DNA repair capacity and consequently increased risk for thyroid cancer.

Background: MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods: We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Results: Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. Conclusion: It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.