Because reduced DNA repair capacity (phenotype) has been suggested as a risk factor for squamous cell carcinoma of the head and neck (SCCHN), newly-identified DNA repair gene polymorphisms (genotype) may also be implicated in risk. To test this hypothesis, we conducted a case-control study of 203 SCCHN patients and 424 control subjects (matched for age, sex and ethnicity) to investigate the role of two XRCC1 polymorphisms (XRCC1 26304 T and XRCC1 28152 A, respectively) in SCCHN. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (CI). A total of 180 cases (88.7%) and 363 controls (85.6%) lacked the XRCC1 26304 T allele [adjusted OR = 1.34 (CI, 0.80-2.25)]. Lack of this polymorphism was a significant risk factor specifically for cancers of the oral cavity and pharynx [adjusted OR = 2.46 (CI, 1.22-4.97)]. Thirty-two cases (15.8%) and 46 controls (10.8%) were homozygous for the XRCC1 28152 A allele [adjusted OR = 1.59 (CI, 0.97-2.61) for all cases, and 1.41 (CI, 0. 80-2.48) for oral and pharyngeal cancer only]. Furthermore, when the two genotypes were combined into a three-level model of risk, a polymorphism-polymorphism interaction of increasing risk (trend test, P = 0.049) was evident: OR = 1.0 for those with neither risk genotype (referent group), adjusted OR = 1.51 (CI, 0.87-2.61) for those with either risk genotype, and 2.02 (CI, 1.00-4.05) for those with both risk genotypes. For oral and pharyngeal cancer, this trend was even more pronounced with the adjusted OR = 2.68 (CI, 1.28-5.61) for those with either risk genotype, and 3.22 (CI, 1.33-7.81) for those with both risk genotypes. The findings support the hypothesis that a polymorphic XRCC1 DNA repair gene contributes to risk of developing SCCHN.

DNA repair capacity is central in maintaining normal cellular functions. Variants of several DNA repair genes,including the nucleotide excision repair gene XPD, have been described recently. Because we previously reported that patients with squamous cell carcinoma of the head and neck (SCCHN) had lower DNA repair capacity than healthy controls, we hypothesized that inherited polymorphisms of XPD may contribute to genetic susceptibility to SCCHN, a tobacco-related cancer. To test this hypothesis, we conducted a hospital-based case-control study of 189 SCCHN patients and 496 cancer-free controls who were frequency-matched on age, gender and smoking status. All subjects were non-Hispanic whites. Two XPD polymorphisms (C22541A and A35931C) were typed using the restriction enzymes TfiI and PstI, respectively. Multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In the controls, the frequencies of the variant 22541A and 35931C alleles were 44.7% and 33.8%, respectively. The frequency of the 22541A homozygous genotype (22541AA) was lower in cases (15.9%) than in controls (20.4%) but was not associated with risk (adjusted OR = 0.90; 95% CI = 0.52-1. 56) for SCCHN. The frequency of the 35931C homozygous genotype (35931CC) was higher in cases (16.4%) than in controls (11.5%) and associated with a borderline increased risk (adjusted OR = 1.55; 95% CI = 0.96-2.52) for SCCHN. The risk was higher in older subjects (OR = 2.22; 95% CI = 1.03-4.80), current smokers (OR = 1.83; 95% CI = 0.79-4.27) and current drinkers (OR = 2.59; 95% CI = 1.25-5.34) in the stratification analysis. These results suggest a gene-environment interaction, but this did not reach statistical significance. The findings are limited due to the relatively small numbers in the subgroups and need to be verified by further investigations.

Objective: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, χ 2 , Fisher's exact test, and Woolf's method for odds ratio (OR). Results: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype). Conclusion: In addition to the association of SpA with HLA-B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA.

This study investigates the association between PON1, PON2 polymorphisms and diabetic nephropathy (DN) in patients with Type II diabetes mellitus.The prevalence of diabetic nephropathy is 30 to 40 % in patients with Type I (insulin-dependent) diabetes mellitus or with Type II (non-insulin-dependent) diabetes mellitus. Diabetic nephropathy is not fully explained by traditional risk factors; therefore, genetic factors are strongly suspected.Paraoxonase genes comprise a multigene family in chromosome 7 [1]. Paraoxonase1 (PON1) is an enzyme bound to HDL which prevents the oxydation of LDL and HDL. Two PON1 polymorphisms have been identified: PON1 Arg/Gln 192 and PON1 Met/ Leu 55 [2] and these PON1 polymorphisms have been associated with coronary heart disease (CHD) in diabetic and non-diabetic subjects.Two PON2 AbstractAims/hypothesis. Paraoxonase is a member of a multigene family of three genes. Paraoxonase2 gene polymorphisms have been associated with coronary heart disease in non-diabetic patients and with an increased fasting glycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus. We tested the hypothesis of whether paraoxonase1 and paraoxonase2 polymorphisms were associated with diabetic nephropathy. Methods. Our case-control study of 299 Swiss patients with Type II diabetes included 147 patients with confirmed diabetic nephropathy. Results. In univariate analyses the two paraoxonase2 polymorphisms were associated with diabetic nephropathy. When subjected to multivariate analyses, both paraoxonase2 polymorphisms remained statistically associated with diabetic nephropathy independent of traditional risk factors (paraoxonase2±148: OR = 2.53, p = 0.003; paraoxonase2±311: OR = 2.67, p = 0.002). In addition, BMI interacted with paraoxonase2 polymorphisms as a risk factor of nephropathy. Conclusions/interpretation. The paraoxonase2 gene polymorphisms were significantly associated with diabetic nephropathy independent of traditional risk factors in Type II diabetic patients. The susceptibility to diabetic nephropathy was intensified by the degree of obesity. Pathophysiological pathways should be investigated and could be involved in insulin resistance or lipids metabolism or both. [Diabetologia (2001) 44: 104±107]

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