Table 2.
Study | GWAS vs. Candidate gene | Study design | Replication study | Results |
---|---|---|---|---|
Any solid | ||||
Best et al****, 201170 | SMN GWAS |
Case-control Cases (discovery: n=100; replication: n=62): childhood and adult-onset primary cancers Cancer controls (discovery: n=89; replication: n=71): childhood and adult-onset cancer survivors (matched on primary diagnosis) |
Yes | Two variants at chromosome 6q21 (rs4946728 [OR=11.4, 95%CI, 3.2–40.3]; rs1040411 [OR=6.6, 95%CI, 3.2–13.5]) were associated with SMNs in childhood HL survivors. The variants comprise a risk locus associated with decreased basal expression of PRDM1 and impaired induction of PRDM1 protein after radiation exposure. |
Mertens et al*, 200493 |
Candidate gene GSTM1, GSTT1, XRCC1 |
Cohort study Cohort (n=650): Childhood HL survivors of which 178 patients were diagnosed with SMNs |
No | Individuals lacking GSTM1 were at increased risk of any SMN (OR=1.5, 95%CI, 1.0–2.3). |
Radiation-related breast cancer | ||||
Bernstein et al***, 201023 |
Candidate gene Full mutation screen of ATM gene |
Case control Cases (n=708): breast cancer patients with contralateral breast cancer (adult-onset) Controls (n=1397): U/L breast cancer (adult-onset) |
No | Among women who carried a rare, deleterious ATM missense variant, radiation exposure was associated with a statistically significantly higher risk of contralateral breast cancer compared with unexposed women who carried the wild-type genotype (0.01–0.99 Gy: RR=2.8, 95%CI, 1.2–6.5; ≥1 Gy: RR=3.3, 95%CI, 1.4–8.0) or compared with unexposed women who carried the same deleterious missense variant (0.010.99 Gy: RR=5.3, 95%CI: 1.6–17.3; ≥1.0 Gy: RR=5.8, 95% CI: 1.8–19.0, Ptrend=0.04) |
Brooks et al***, 201294 |
Candidate gene CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1 |
Case-control Cases (n=649): breast cancer patients with contralateral breast cancer (adult-onset) Controls (n=1284): U/L breast cancer (adult-onset) |
No | Carriers of a RAD50 haplotype exposed to ≥1 gray had an increased risk of contralateral breast cancer compared with unexposed carriers (RR=4.3, 95% CI, 1.9–9.6) with an excess relative risk per Gray=2.1 (95% CI, 0.6–5.3) |
Radiation-associated meningioma | ||||
Hosking et al***, 201174 | Family-based association test (FBAT) |
Family-based association study 15 families segregating radiation-associated meningioma using high-density SNP arrays (adults) |
No | The strongest haplotype associations were attained at 18q21.1 (p=7.5 × 10−5), 18q21.31 (p=2.8 × 10−5) and 10q21.3 (p=1.6 × 10−4). The 18q21.1 and 10q21.3 associations provide support for variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL, CTNNA3 genes as risk factors for radiation- associated meningioma. |
Head and Neck Cancer | ||||
Gal et al*, 200585 |
Candidate gene XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, MGMT Leu84Phe, Val143Ile |
Cohort study Cohort (n=246): 18–65 yo with oral cancer; 88 developed a head and neck SMN |
No | A significant increased risk of SMNs (all sites combined; upper airway digestive tract sites; head and neck squamous cell carcinomas) was observed among XRCC3 241 Met allele homozygotes (HR=2.65–3.44, p<0.02). |
Jin et al***, 201386 |
Candidate gene P53, p73, p14ARF, MDM2, MDM4 |
Cohort study Cohort (n=1283): Adults with squamous cell carcinoma of the head and neck diagnosed between 1995 and 2007; of these 120 developed an SMN |
No | SMN risk increased with increasing number of risk genotypes (Ptrend<0.0001). Compared with the low risk group (0–3 combined risk genotypes), both the medium-risk (4–5 combined risk genotypes) and high-risk (6–9 combined risk genotypes) groups had significantly increased risk of SMNs (HR: 1.6, 95% CI: 1.0–2.6; HR: 3.0, 95%CI, 1.8–5.0, respectively) |
Zhang, et al***. 2012,87 |
Candidate gene p53 codon 72 and p73 G4C14-to-A4T14 |
Cohort study Cohort (n=1269)of adults with squamous cell carcinoma of the head and neck; of these 109 developed an SMN |
No | Patients with p53 WP + PP and p73 GC/GC genotypes had an increased risk of SMNs compared with the corresponding p53 WW and p73 GC/T + AT/AT genotypes. After combining the 2 polymorphisms, a significantly increased risk of SMN was observed in the high risk group (p53 P carriers and p73 GC/GC) compared with the low risk group (p53 WW and p73 AT carriers). |
Radiation-associated papillary carcinoma of thyroid gland | ||||
Akulevich*, 200990 |
Candidate gene ATM, XRCC1, TP53, XRCC3, MTF1 |
Case-control Cases (n=123): Childhood primary cancers Healthy controls (596): Children |
No | In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype was associated with radiation-induced papillary thyroid carcinoma (OR=2.1, 95% CI, 1.2–3.8) |
The study populations included primarily children
The study populations included primarily adults, although some children were also included
The study populations included primarily adults
The study population includes an equal mix of children and adults