Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.
Prostate cancer is the most common nonskin malignancy among men worldwide. In the US, an estimated 233,000 new cases and 29,480 deaths are expected in 2014 [
The cell cycle checkpoint kinase 2 (
We decided to focus on the 1100delC mutation as it is a frame-shift mutation that abrogates kinase activity and renders the protein ineffective. In the following, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of
An online search in PubMed was performed in December 2013 using the following keywords: (CHEK2∗1100delC prostate), (CHEK2∗1100delC), (CHEK2 prostate), (CHEK2 cancer), or (susceptibility gene prostate). Respectively, the PubMed provided 9, 36, 98, 326, and 1,590 results. References of the identified studies were scrutinized in order to make sure all possible studies could be included in this review. The titles and abstracts of articles identified by PubMed were reviewed and unmatched articles which did not meet with selection criteria were excluded. We included articles that examined
In case results from the same individuals were reported in more than one publication, the newest or most informative article was selected [
Characteristics and results of 5 prostate cancer studies.
Carrier/Total | Population | Country | OR/HR (95% CI) |
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Ref. |
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21/3,750 | Unselected cases | PL | 3.2 (1.4–7.5) | 0.009 | [ |
4/412 | Familial cases | 5.5 (1.6–19.0) | 0.01 | ||
7/3,956 | Controls | Reference | |||
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1/145 | Without family history | SW | 0.70 (0.07–6.78) | 0.76 | [ |
4/254 | Familial cases | 1.61 (0.36–7.27) | 0.53 | ||
3/305 | Controls | Reference | |||
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7/537 | Unselected cases | FI | 3.14 (0.65–15.16) | 0.15 | [ |
4/120 | Familial cases | 8.24 (1.49–45.54) | 0.02 | ||
2/480 | Controls | Reference | |||
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4/178 | Cases | US | NA | NA | [ |
1/400 | Without family history | NA | NA | ||
1/298 | Familial cases | NA | NA | ||
0/423 | Controls | NA | NA | ||
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2/114 | Cases | DE | 2.3 (0.6–9.5) | NA | [ |
21/4,094 | Controls | Reference | |||
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PL: Poland, SW: Sweden, FI: Finland, US: United States, DE: Denmark, NA: not available.
Characteristics and results of 7 excluded prostate cancer studies.
Carrier/Total | Population | Country | OR/HR (95% CI) |
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Ref. |
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14/1,864 | Unselected cases | PL | 3.5 (1.6–7.5) | 0.002 | [ |
3/249 | Familial cases | 5.6 (1.6–19.9) | 0.02 | ||
12/5,496 | Controls | Reference | |||
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3/84 | Cases | US | NA | NA | [ |
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Families with breast cancer history | UK, NE, DE, US | 2.68 (ratio of carrier RR versus noncarrier RR) | 0.26 | [ | |
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3/690 | Unselected cases | PL | 2.1 (0.5–9.4) | 0.32 | [ |
1/98 | Familial cases | 4.9 (0.5–44.6) | 0.11 | ||
4/1,921 | Controls | Reference | |||
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3/690 | Unselected cases | PL | 1.74 (0.48–6.35) | 0.39 | [ |
10/4,000 | Controls | Reference |
PL: Poland, UK: United Kingdom, NE: Netherlands, DE: Denmark, US: United States, NA: not available.
The five included studies examined CHEK2∗1100delC heterozygosity and risk of cancer in 6,228 prostate cancer cases including 830 familial cases and 9,258 male controls. Selected characteristics of studies are shown in Table
Cybulski et al. sequenced the coding region of
Mayo investigators [
Seppälä et al. reported that the frequency of
Weischer et al. reported whether
However, Wagenius et al. could not confirm results from Cybulski study. They assessed the significance of the
Thompson et al. assessed the risk of various cancers in association with
We reviewed the current knowledge of the role of a genetic variant, 1100delC, of
The
Bahassi et al. demonstrated the biological role of
A role of
Characteristics and results of various cancer studies.
Cancer Site | Case/control | Population | Country | OR/HR (95% CI) |
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Ref. |
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Breast | (459) 25,571/(179) 30,056 | (Meta-analysis) | 3.01 (2.53–3.58) | [ | ||
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Breast | 1,828/7,030 | (Cases/controls) | UK, FI, NE, GE, RU | 6.43 (4.33–9.56) | <0.0001 | [ |
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Breast | (120) 2,554/(37) 3,267 | (Familial cases) | NE | 4.30 (2.97–6.25) | <0.0001 | [ |
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Breast | 3,882/8,609 | (Cases/controls) | CA | 2.6 (1.1–5.8) | 0.05 | [ |
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Breast | 75/300 | (Cases/controls) | SW | 2.5 | 0.26 | [ |
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Breast | 708 bilateral + 1,395 unilateral | (Cases only) | US, DE | 1.8 (0.6–5.4) | [ | |
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Breast | 71/1,692 | (Cases/controls) | NE | 4.1 (1.2–14.3) | 0.05 | [ |
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Breast | (0) 668 | (Cases only) | MAL | [ | ||
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Breast | 1,101/4,665 | (Cases/controls) | DE | 1.2 (0.7–2.1) | [ | |
(Breast) | 3.2 (1.0–9.9) | |||||
(Colorectal) | 1.6 (0.4–6.5) | |||||
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Breast | 161/153 | US | NS | [ | ||
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Breast | 2,311/496 | (Female cases/controls) | CA | 6.65 (2.37–18.68) | [ | |
US | 0.12 (0.02–0.89) | |||||
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Breast | 1,071/1,620 | UK, NE, CA, US, GE | 1.1% of controls versus 5.1% of cases | 0.00000003 | [ | |
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Breast | 300/1,665 | US | 1% among cases versus 0.3% of controls | 0.1 | [ | |
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Breast | 10,860/9,065 | (Aggregate) | UK, NE, FI, GE, AU | 2.34 (1.72–3.20) | 0.0000001 | [ |
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Breast | (0) 493 | (Cases only) | KO | [ | ||
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Breast | 903/1,016 | IR | 0.5% of cases versus 0.1% of controls; 5.65 (0.66–48.46) | 0.09 | [ | |
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Breast | 1,479 | (Cases only) | US | 2.1 (1.0–4.3) | 0.049 | [ |
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Breast | 1,035/1,885 | (Positive family history) | FI | 2.27 (1.11–4.63) | 0.021 | [ |
(Bilateral) | 6 (1.87–20.32) | 0.007 | ||||
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Breast | 300 | (Cases only) | AU | 0.6% of cases | [ | |
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Breast | 237/331 | (Cases/controls) | NE | 11.4% of cases versus 2.8% of controls | 0.001 | [ |
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Breast | 302 | (Cases only) | RU | 3% of cases. | [ | |
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Breast | (0) 400/(0) 400 | SP | [ | |||
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Breast | (0) 196/(0) 1,024 | CHL | [ | |||
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Breast | (0) 102 | (Familial cases) | US | [ | ||
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Breast | 507/513 | (Cases/controls) | FR | 1.14% in cases versus 0.29% in controls; 5.18 | 0.004 | [ |
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Breast | 5,953 | (Cases only) | PL | 3.6 (2.1–6.2) | 0.0001 | [ |
(Prostate) | 4.4 (2.2–8.7) | 0.0001 | ||||
(Colon) | 4.2 (2.4–7.8) | 0.0001 | ||||
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Breast | 8,612 | (Cases only) | UK | [ | ||
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Breast, Colorectal | 75 | (Cases only) | SW | 2.5% | 0.26 | [ |
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Breast | (3) 1,434 | (Cases only) | NE | 3.4 (0.4–32.6) | 0.3 | [ |
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Melanoma | (15) 1,889/(59) 12,801 | (Combined) | 1.79 (1.02–3.17) | [ | ||
DE | 2.01 (1.03–3.91) | |||||
GE | 1.42 (0.46–4.31) | |||||
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Melanoma | (18) 2,619/(67) 17,481 | (Meta-analysis) | 1.81 (1.07–3.05) | [ | ||
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Colorectal | (8) 818/(5) 760 | (Unselected) | SW | 1.49 (0.49–4.58) | 0.48 | [ |
(2) 174/(5) 760 | (Familial) | 1.76 (0.34–9.13) | 0.50 | |||
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Colorectal | 369 | (Cases only) | NE | 4.2% HNPCC cases | [ | |
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Colorectal | 4,194/10,010 | (Meta-analysis) | 2.11 (1.41–3.16) | 0.0003 | [ | |
1,050/3,784 | (Familial) | 2.80 (1.74–4.51) | <0.0001 | |||
652/2,115 | (Sporadic) | 1.45 (0.49–4.30) | 0.50 | |||
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Colorectal | (0) 210/(0) 446 | (Cases/controls) | TUK | [ | ||
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Esophagus | (8) 551/(9) 644 | (Cases/controls) | NE | 1.04 (0.35–3.06) | 0.94 | [ |
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Head & Neck | (0) 91 | (Case only) | GE | [ | ||
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Ovary | (2) 268/(1) 821 | (Cases/controls) | RU | 6.17 (0.56–68.3) | 0.09 | [ |
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Pancreas | (0) 270/(0) 683 | (Cases/controls) | CZ | [ | ||
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Leukemia | (8) 973/(18) 1,620 | (Cases/controls) | UK | 0.74 (0.32–1.7) | [ | |
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Lung | (0) 457 | (Cases only) | NE | [ | ||
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Brain | (0) 79 | (Familial cases) | FR | [ |
UK: United Kingdom, FI: Finland, NE: Netherlands, GE: Germany, RU: Russia, CA: Canada, SW: Sweden, US: United States, DE: Denmark, GE: Germany, MAL: Malaysia, AU: Australia, KO: Korea, IR: Ireland, SP: Spain, CHL: Chile, FR: France, PL: Poland, TUK: Turkey, and CZ: Czech.
The
Xiang et al. [
Weischer et al. performed an association study on the Danish and German population while also conducting a meta-analysis with four different studies [
However, several studies reported inconsistent results. Three small studies were performed to see whether there was an association between
In an esophageal cancer study, Koppert et al. found 1.5% of 551 cases and 1.4% of 644 controls carry the
Only one study described
Sellick et al. found that there may be a low penetrance effect on risk of chronic lymphocytic leukemia (CLL) based on 973 cases and 1,620 UK controls. But there was no significant association found between
In the lung cancer study, Huijts et al. could not confirm an association between
Results from multiorgan cancer study by Cybulski et al. suggested an increased risk in thyroid and renal cancers although they were not in the significant level [
The studies performed in Malaysia [
We are aware of some limitations of this meta-analysis. First, because of the lack of the individual level data of the reviewed studies, our reports were based on unadjusted published estimates; therefore, we were unable to adjust them by possible confounders such as age and other environmental risk factors. Second, the prevalence of
The screening for the
Because odds ratios were reported for prostate cancer with this mutation range between 2.0 and 3.0, it is reasonable to suggest screening for
All authors declare that there are no competing financial interests.
The development of this paper was supported in part by R01CA128813 (PI: Park).