The frequency distributions of the selected characteristics for the ALL patients and control groups are summarized in Table 1. Their mean age (SD) of the patients and the controls was 5.87 (3.6) and 7.8 (5.2) years. Gender, parent’s smoking habits and family cancer history differed significantly between cases and controls (P < 0.05). The cases had a significantly higher percentage of those characteristics in comparison with the controls. Our results showed that cigarette smoking habit of parents to be risk factor for ALL. However, the age of diagnosis, blood type and T vs. B immune phenotype distribution did not differ significantly between the cases and controls (P > 0.05) (data not shown).
Table 1
Frequency distributions of selected variables between the acute lymphoblastic leukemia cases and controls
Variables | Cases (n = 99) | Controls (n = 200) | OR (95% CI) | P value* |
| n (%) | n (%) | | |
Gender | | | | |
Male | 64 (64%) | 96 (48%) | 1.00 | |
Female | 36 (36%) | 104 (52%) | 0.51 (0.31–0.85) | 0.009 |
Parents Smoking habit | | | | |
No | 52 (52%) | 120 (64.2%) | 1.00 | |
Yes | 48 (48%) | 67 (35.8%) | 1.77 (1.68–2.94) | 0.027 |
Family Cancer history** | | | | |
No | 26 (57.8%) | 149 (88%) | 1.00 | |
Yes | 19 (42.2%) | 42 (22%) | 2.608 (1.311–5.385) | 0.006 |
*P associated with either Student's t-test or chi-square test and Fisher's exact test. |
**Family history of Acute lymphoblastic leukemia in the first-degree relatives. |
Table 2 shows genotype distributions of the XRCC7 G6721T (rs7003908) polymorphism among the ALL patients and the control and the associations with the risk of ALL. The genotype frequencies of polymorphism in controls (χ2 = 5.03, df = 1, P = 0.515) and patients (χ2 = 2.04, df = 1, P = 0.165) were among Hardy-Weinberg equilibrium. The GT (OR = 1.485, 95% CI: 0.765–2.334, P = 0.243) and TT (OR = 1.655, 95% CI: 00.875–3.128, P = 0.121) in comparison with GG had no significant effect on the risk of ALL (Table 2). The association between ALL cancer risk and XRCC7 G6721T polymorphism was not assessed, although a few studies have analyzed correlation of this polymorphism with the risk of other cancers. The assumption was that dysfunction of human X-ray repair cross-complementing group 7 gene (XRCC7) might be involved in cancer susceptibility. It seems to be possible, based on the function of gene and by product of it, although the investigated intronic XRCC7 G6721T (rs.7003908) polymorphism seems to be controversial. Two studies suggested that XRCC7 G6721T polymorphism might contribute to cancer susceptibility for prostate and renal cell carcinoma [9,12]. On the contrary, Nasiri et al. [10] did not find any correlation between XRCC7 G6721T polymorphism and breast cancer, which was in line with our finding.
Table 2
Association between polymorphisms of XRCC7 and risk of ALL
XRCC 7 Polymorphism | Controls | Cases | OR | 95% CI | P value |
GG | 54 | 19 | 1 | References | |
GT | 67 | 34 | 1.485 | 0.765–2.334 | 0.243 |
TT | 79 | 46 | 1.655 | 0.875–3.128 | 0.121 |
Moreover, after adjusting gender and history of family cancer, insignificant results were obtained for GT and TT genotype in comparison with GG (data are not shown). The results in Table 3 shows the distribution of XRCC7 G6721T polymorphism between the ALL and control groups among positive parent’s smoking habits. The reference was individuals with negative parents smoking habit and GG genotype. The GT (OR = 1.637, 95% CI: 0.83–3.229, P = 0.155) genotype had no effect on the risk of ALL, but TT (OR = 1.996, 95% CI: 1.033–3.858, P = 0.04) genotype had significant effect on risk of ALL, in comparison with the GG genotype. Overall, there was an interaction between XRCC7 G6721T polymorphism, TT genotype, and positive parents smoking habit with the ALL susceptibility. No statistical significant differences were observed between the XRCC7 G6721T genotypes regarding gender, family history, IPT and TLC (data are not shown).
Table 3
The ALL cancer risk by positive parents smoking habit and the XRCC7 polymorphism
XRCC 7 Polymorphism | Controls | Cases | OR (95% CI) ‡ | P value |
GG | 27 | 11 | 1 | |
GT | 22 | 30 | 1.637(0.83–3.22) | 0.15 |
TT | 18 | 7 | 1.996(1.03–3.86) | 0.04 |
‡ORs were adjusted for parents smoking status use in a logistic regression model |
According to the role of the NHEJ pathway in DNA repair, it is a logical possibility that the XRCC7 polymorphism might be regulating the risk of cancer accompanied by environmental risk factors such as smoking habit [11]. Carcinogens might enhance DSBs, leading to the genetic instability by increasing the rate of cancer development. It is known that the XRCC7 gene is responsible for repairing most DSBs [6]. Consequently, the variants of the XRCC7 gene could be expected to have an effect on DSB repair when people are exposed to carcinogens such as a Tobacco smoke.