**3.2.3** *XPA* **G23A**

546 DNA Repair

0.4-1.0) among homozygous carriers of the *XPD* 751Gln allele (Stern et al., 2006). The result was not stratified for ethnicity (Caucasian, African-American, Latinos, Asian-Pacific Islander). When excluding the 1 case and the 17 controls of Latinos, the OR increased to 0.9 (confidence intervals were not reported). An interaction between the *XPD* Lys751Gln polymorphism and alcohol consumption was observed (P=0.04), with higher risk of adenomas among ever-drinkers carrying the *XPD* 751 Gln/Gln genotype (OR=2.5, CI: 1.2- 5.2) compared with never-drinkers carrying the same genotype. There was no interaction between the polymorphisms *XPD* Lys751Gln or *XPD* Asp312Asn, respectively, and alcohol consumption on risk of colorectal cancer in our Danish study (Hansen et al., 2007) and in the

In a family-based case-control study using a case-only design, an interaction was observed between the two polymorphisms, *XPD* Lys751Gln and *XPD* Asp312Asn, and intake of heavily browned red meat on colorectal cancer risk (Joshi et al., 2009). Intake of red meat heavily brown on the outside or inside increased the risk for colorectal cancer only among carriers of the *XPD* codon 751 Lys/Lys genotype or the *XPD* codon 312 Asp/Asp genotype (case-only interaction P <0.006). There was no association between the meat intake and colorectal cancer risk when the individuals carried at least one copy of the Asn321 or Gln751 alleles. The results remained statistically significant after accounting for multiple testing. No interaction was observed in our Danish study between the two *XPD* polymorphisms and

A higher risk of colorectal cancer has been observed among Ashkenazi Jews below 50 years of age when diagnosed (Starinsky et al., 2005). The risk was higher among carriers of the *XPD* 751Gln allele, but it may be a chance finding due to low number of cases (only 15 cases were diagnosed before their 50 years birthday). Furthermore, the Ashkenazi population is known to have particular genetic characteristics, why the result may not be generalized to

A large study from Taiwan observed a non-significant tendency for higher risk of colorectal cancer among men carrying the *XPD* 751Gln allele (OR=1.5, CI: 0.9-2.3), while no association was observed for women (OR=0.9, CI: 0.6-1.5) (Yeh et al., 2007). A similar tendency for a gender specific effect of the *XPD* Lys751Gln polymorphism was observed in our Danish study, with lower risk of colorectal cancer among women carrying the variant allele of *XPD* Lys751Gln with an IRR less than 0.62 among carriers of the *XPD* 751Gln allele, compared to women carrying the wild type allele (Hansen et al., 2007) . No association was found among men. The gender differences could hypothetically be caused by a hormonal interaction. However, we observed no interaction between the use of hormone replacement therapy among women and the polymorphism. Thus, we did not find the hypothesis plausible and

In our Danish study and in a Turkish study by Engin *et al*. (Engin et al., 2010) , the *XPC* Lys939Gln polymorphism was not associated with risk of colorectal cancer (Hansen et al., 2007). However, we did observe an interaction between the polymorphism and intake of red meat, with an IRR of 3.70 (CI: 1.70-8.04) for colorectal cancer per 100g red meat intake per day among homozygous carriers of the *XPC* Lys939Gln variant allele (Hansen et al., 2007) . In the light of the sample size and the multiple comparisons being made, this result may be a chance finding. The association was not statistically significant after a Bonferroni

Singapore Chinese study (Stern et al., 2007).

other populations.

**3.2.2** *XPC* **Lys939Gln** 

correction.

intake of red meat on risk of colorectal cancer (Hansen et al., 2007).

conclude that our result in the Danish study may be a chance finding.

To our knowledge, only three studies have been published on the association of polymorphisms in the *XPA* gene with risk of colorectal cancer: The studies by Berndt *et al*., Joshi *et al*., and our study. For a polymorphism positioned in the *XPA* 5´ UTR region, a lower risk for colon cancer cancer was observed among carriers of the T-allele (OR=0.4, 95% CI: 0.2-0.8) compared with homozygous carriers of the C-allele (Joshi et al., 2009) . There was no association for risk of rectal cancer. No association was observed of the *XPA* G23A polymorphism (Hansen et al., 2007) or a polymorphism in the 3´ un-translated region of *XPA* (Berndt et al., 2006) with risk of colorectal cancer.
