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author:("Lee, young-Mu")
1.  p73 G4C14 to A4T14 polymorphism is associated with colorectal cancer risk and survival 
AIM: To analyze the association between the p73 G4C14-to-A4T14 polymorphism (a.k.a., the GC/AT variation) and colorectal cancer risk and survival in the Korean population, and to evaluate the relationships between p73 polymorphism and the p73 protein expression or clinicopathological characteristics of colorectal cancer.
METHODS: Three hundred and eighty-three histologically confirmed cases and 469 healthy controls, recruited at one teaching hospital in Pusan, Korea from 2001 and 2007, were genotyped for p73 G4C14-to-A4T14 by PCR with confronting two-pair primers (PCR-CTPP) and the expression profile of p73 in cancer tissues (n = 383) was analyzed by immunohistochemistry.
RESULTS: Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model adjusted for age and gender. Compared with the GC/GC genotypes, the GC/AT and AT/AT genotypes were significantly associated with colorectal cancer risk (GC/AT vs GC/GC: OR = 1.46, 95% CI: 1.10-1.94; AT/AT vs GC/GC: 1.72, 0.98-3.03; Ptrend = 0.01). When stratified by age and gender, the association was restricted to those less than 60 years of age (GC/AT or AT/AT vs GC/GC: 2.22, 1.39-3.55) and male (GC/AT or AT/AT vs GC/GC: 1.91, 1.31-2.77). The expression of p73 was associated with invasion depth (P = 0.003) and advanced Duke’s stage (P = 0.06) of colorectal cancer. The patients with the GC/GC genotype were associated with worse survival compared with those with the other genotypes (P = 0.02). However, no significant relationship was observed between the p73 G4C14-to-A4T14 polymorphism and p73 protein expression in cancer tissues.
CONCLUSION: Our results suggest that the p73 GC/AT polymorphism is associated with an increased colorectal cancer risk and survival in the Korean population.
doi:10.3748/wjg.v16.i35.4448
PMCID: PMC2941069  PMID: 20845513
p73 G4C14 to A4T14 polymorphism; Colorectal cancer
2.  DNA Methylation in Peripheral Blood: A Potential Biomarker for Cancer Molecular Epidemiology 
Journal of Epidemiology  2012;22(5):384-394.
Aberrant DNA methylation is associated with cancer development and progression. There are several types of specimens from which DNA methylation pattern can be measured and evaluated as an indicator of disease status (from normal biological process to pathologic condition) and even of pharmacologic response to therapy. Blood-based specimens such as cell-free circulating nucleic acid and DNA extracted from leukocytes in peripheral blood may be a potential source of noninvasive cancer biomarkers. In this article, we describe the characteristics of blood-based DNA methylation from different biological sources, detection methods, and the factors affecting DNA methylation. We provide a comprehensive literature review of blood-based DNA methylation as a cancer biomarker and focus on the study of DNA methylation using peripheral blood leukocytes. Although DNA methylation patterns measured in peripheral blood have great potential to be useful and informative biomarkers of cancer risk and prognosis, large systematic and unbiased prospective studies that consider biological plausibility and data analysis issues will be needed in order to develop a clinically feasible blood-based assay.
doi:10.2188/jea.JE20120003
PMCID: PMC3798632  PMID: 22863985
DNA methylation; blood-based biomarker; serum; plasma; leukocyte; peripheral blood
3.  The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer 
BMC Cancer  2012;12:193.
Background
Although a number of experimental studies have suggested the role of lipocalin-2 (LCN2) and matrix metalloproteinase-9 (MMP-9) in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the levels of lipocalin-2 and MMP-9 and breast cancer survival.
Methods
Preoperative serum levels of lipocalin-2 and MMP-9 were measured in 303 breast cancer patients and 74 healthy controls recruited between 2004 and 2007. We examined the association between lipocalin-2 and MMP-9 levels and disease-free survival (DFS) using Cox proportional hazard regression model.
Results
The serum levels of lipocalin-2 and MMP-9 were not significantly different between patients and controls (P > 0.05). Elevated lipocalin-2 and MMP-9 levels were associated with reduced DFS of breast cancer ( Ptrend = 0.029 and Ptrend = 0.063, respectively). When lipocalin-2 and MMP-9 levels were categorized based on the combined risk score, patients with higher levels of both lipocalin-2 and MMP-9 exhibited poor DFS compared to patients with lower levels (Ptrend = 0.004). Furthermore, these effects were profound in patients with BMI less than 25 kg/m2 (adjusted hazard ratio (aHR), 3.17; 95% confidence intervals (CI), 1.66-6.06, Ptrend < 0.001) or lymph-node negative breast cancer (aHR, 5.36; 95% CI, 2.18-13.2, Ptrend < 0.001).
Conclusions
Our study suggests that the elevated levels of lipocalin-2 and MMP-9 are associated with reduced breast cancer survival, particularly in patients with lower BMI and lymph-node negative breast cancers.
doi:10.1186/1471-2407-12-193
PMCID: PMC3479006  PMID: 22640376
4.  Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival 
BMC Cancer  2012;12:195.
Background
Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown.
Methods
We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died.
Results
Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07).
Conclusions
Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.
doi:10.1186/1471-2407-12-195
PMCID: PMC3487887  PMID: 22639842
microRNA biogenesis pathway; Breast cancer; Survival; Single nucleotide polymorphism
5.  A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study 
Introduction
Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.
Methods
To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.
Results
In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).
Conclusions
This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.
doi:10.1186/bcr3158
PMCID: PMC3446390  PMID: 22452962
6.  No Association Between Functional Polymorphisms in COMT and MTHFR and Schizophrenia Risk in Korean Population 
Epidemiology and Health  2010;32:e2010011.
OBJECTIVES
Common genetic SNPs in two genes, encoding catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR), which are interconnected with COMT gene regulation, have been reported to contribute to schizophrenia risk. In this study, we evaluated the association between functional polymorphisms in COMT and MTHFR and schizophrenia risk with a case-control study in a Korean population.
METHODS
We performed a case-control study by genotyping analysis using 360 cases and 348 controls in Korean subjects to determine the association between functional polymorphisms in COMT and MTHFR and schizophrenia risk.
RESULTS
Four functional SNPs in COMT (Val158Met and rs165599) and MTHFR (C677T and A1298C) were genotyped by primer extension assay. None of the genotype distributions for the four SNPs was significantly different between cases and controls. Stratified analysis did not show any significant gender difference for any polymorphism. In addition, we found no evidence of a gene-gene interaction in the analysis of combined genotypes.
CONCLUSION
Our results suggest no significant association between the selected functional polymorphisms of COMT or MTHFR in Korean schizophrenia subjects. However, further studies are required to confirm our findings in a larger number of subjects.
doi:10.4178/epih/e2010011
PMCID: PMC3013321  PMID: 21217836
Catechol-O-methyltransferase; Schizophrenia; Methylenetetrahydrofolate reductase; Polymorphism
7.  Genetic variation in cell cycle and apoptosis related genes and multiple myeloma risk 
Leukemia research  2009;33(12):1609-1614.
Genetic variation may be an important risk factor for multiple myeloma. A hallmark of tumor formation and growth is cell cycle dysregulation and apoptosis avoidance. We previously reported the association of genetic variation in caspase genes, the apoptotic-regulating family, and multiple myeloma risk. To further examine if genetic variation in key cell cycle and apoptosis genes alters multiple myeloma risk, we genotyped 276 tag SNPs in 27 gene regions in a population-based case-control study of non-Hispanic Caucasian women (108 cases; 482 controls) in Connecticut. Logistic regression assessed the effect of each SNP on multiple myeloma risk and the minP test assessed the association at the gene region level. Three gene regions were significantly associated with risk of multiple myeloma (BAX minP = 0.018, CASP9 minP = 0.025, and RIPK1 minP = 0.037). Further explorations identified the most significant variant of BAX, RIPK1, and CASP9 to be rs1042265, rs9391981, and rs751643, respectively. The A variant at rs1042265 (ORGA+AA = 0.40, 95%CI = 0.21 – 0.78) and the C variant at rs9391981 (ORGC+CC = 0.32, 95%CI = 0.12 – 0.81) were associated with a decreased risk of multiple myeloma. The G variant at rs7516435 was associated with an increased risk of multiple myeloma (ORAG = 1.48, 95%CI = 0.94 – 2.32; ORGG = 2.59, 95%CI = 1.30 – 5.15; ptrend = 0.005). Haplotype analyses supported the SNP findings. These findings suggest that genetic variation in cell cycle and apoptosis genes may play a key role in multiple myeloma and warrant further investigation through replication studies.
doi:10.1016/j.leukres.2009.03.013
PMCID: PMC2749910  PMID: 19362737
multiple myeloma; caspase; BAX; RIPK1; cell cycle
8.  Variation in lung cancer risk by smoky coal subtype in Xuanwei, China 
Lung cancer rates in Xuanwei County have been among the highest in China for both males and females, and have been causally associated with exposure to indoor smoky (bituminous) coal emissions that contain very high levels of polycyclic aromatic hydrocarbons. There are numerous coal mines across the County. Although lung cancer risk is strongly associated with use of smoky coal as a whole, variation in risk by smoky coal subtype has not been characterized as yet. We conducted a population-based case-control study of 498 lung cancer cases and 498 controls, individually matched to case subjects on age (±2 years) and sex, to examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) for coal subtype were calculated by conditional logistic regression, adjusting for potential confounders. Overall, smoky coal use was statistically significantly associated with lung cancer risk, as compared to use of smokeless coal or wood (OR=7.7, 95% CI=4.5 to 13.3). Furthermore, there was marked heterogeneity in risk estimates for specific subtypes of smoky coal (test for heterogeneity: p=5.17 × 10−10). Estimates were highest for coal from the Laibin (OR=24.8, 95% CI=12.4 to 49.6) and Longtan (OR=11.6, 95% CI = 5.0 to 27.2) coal types, and lower for coal from other types. These findings strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of coal combustion products can exhibit substantial local variation by specific coal source.
doi:10.1002/ijc.23748
PMCID: PMC2974309  PMID: 18712724
Coal; lung cancer; indoor air pollution; Xuanwei; China
9.  Polymorphisms in innate immunity genes and risk of childhood leukemia 
Human immunology  2010;71(7):727-730.
Objectives
To evaluate whether candidate genes in innate immunity are associated with childhood leukemia, we conducted an association study with the 1,536 SNPs in 203 genes related to innate immunity.
Methods
Incident childhood leukemia cases (n=136) aged from 0 to 18 were recruited from three teaching hospitals in Seoul between 2003 and 2006. Non-cancer controls (n=140) were frequency-matched to cases by age and gender. The information on the characteristics of children and their parents were collected by trained interviewers using structured questionnaire. Candidate genes were selected based on SNP databases (CGAP and SNP500 database), and genotype assay was performed using GoldenGate (Illumina) oligonucleotide pool assay (OPA). False discovery rate (FDR), permutation test, and haplotype analyses were used to identify the SNP with significant association with childhood leukemia. Childhood leukemia risk was estimated as ORs and 95% CIs adjusted for age, gender and birth weight.
Results
Fourteen SNPs in 13 genes (LMAN1, TLR4, STAT4, CCR9, MBP, ZP1, C8B, XDH, C7, C1QG, FGF2, LOC390183, and STAT6) were significantly associated with childhood leukemia risk (FDR p-values <0.05). In particular, LMAN1 rs1127220, TLR4 rs11536897, STAT4 rs13020076, CCR9 rs1471962, and MBP rs10514234 were significant in 5,000 permutation tests (Permutation p-value <0.05). The most significant association with childhood leukemia risk was for the LMAN1 rs1127220 that is in the protein-coding region, this finding was also supported by haplotype analysis.
Conclusions
A number of innate immunity related genes are associated with childhood leukemia, suggesting possible links between the innate immunity system and development of the childhood leukemia.
doi:10.1016/j.humimm.2010.04.004
PMCID: PMC2967770  PMID: 20438785
Childhood Leukemia; Innate Immunity; Single Nucleotide Polymorphism
10.  The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia 
PLoS Genetics  2010;6(8):e1001051.
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Author Summary
Worldwide, approximately 15% of lung cancer cases occur among nonsmokers. Genome-wide association studies (GWAS) of lung cancer conducted in populations of European background have identified three regions on chromosomes 5, 6, and 15 that harbor genetic variants that confer risk for lung cancer. Prior studies were conducted primarily in cigarette smokers, raising the possibility that the associations could be related to tobacco use, lung carcinogenesis, or both. A GWAS of lung cancer among never-smokers is an optimal setting to discover effects that are independent of smoking. Since most women in Asia do not smoke, we conducted a GWAS of lung adenocarcinoma among never-smoking females (584 cases, 585 controls) in Taiwan, and observed a region on chromosome 5 significantly associated with risk for lung cancer in never-smoking women. The finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls. To our knowledge, this study is the first reported GWAS of lung cancer in East Asian women, and together with the replication studies represents the largest genetic association study in this population. The findings provide insight into the genetic contribution of common variants to lung carcinogenesis.
doi:10.1371/journal.pgen.1001051
PMCID: PMC2916850  PMID: 20700438
11.  Personal use of hair dye and cancer risk in a prospective cohort of Chinese women 
Cancer science  2009;100(6):1088-1091.
Although widely studied over the past forty years, personal use of hair dye generally has not been associated with overall cancer risk. The association between hair dye use and risk of bladder and hematopoietic cancers has been less conclusive. Most hair dye studies have been case-control studies conducted in Caucasian populations. We examined the relationship between personal hair dye use and cancer risk in a prospective cohort of 70,366 Chinese women. After an average of 7 years of follow-up, 2,437 women were newly diagnosed with cancer by December 31, 2005. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) of cancer risk associated with hair dye use, adjusting for potential confounding factors. Compared with women who reported no hair dye use, ever users had an overall cancer risk of 0.89 (95% CI: 0.82, 0.97). No significant association was observed for several common cancers, including cancers of the breast (RR: 0.93, 95% CI: 0.78, 1.09), lung (RR: 0.81, 95% CI: 0.62, 1.09), stomach (RR: 0.90, 95% CI: 0.66, 1.21), and colorectum (RR=1.04, 95% CI: 0.84, 1.28). We also found no significant association with most other cancers, including bladder cancer (RR: 1.14, 95% CI: 0.56, 2.35) and hematopoietic cancers overall (RR: 0.89, 95% CI: 0.59, 1.35) or their subtypes, including non-Hodgkin lymphoma, multiple myeloma, and leukemia. We generally found no evidence of an association between personal use of hair dye and cancer risk, although our study is limited by small numbers for certain cancer types.
doi:10.1111/j.1349-7006.2009.01149.x
PMCID: PMC2768318  PMID: 19385970
cancer; cohort study; Cox proportional hazards model; hair dye; relative risk
12.  Nitric oxide synthase gene polymorphisms and prostate cancer risk 
Carcinogenesis  2009;30(4):621-625.
Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in prostate carcinogenesis, potentially modulated by environmental exposures. We evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular NO: NOS2A [inducible nitric oxide synthase (NOS); −2892T>C, Ex16 + 14C>T (S608L), IVS16 + 88T>G and IVS20 + 524G>A] and NOS3 [endothelial NOS; IVS1 − 762C>T, Ex7 − 43C>T (D258D), IVS7 − 26A>G, Ex8 − 63G>T (E298D) and IVS15 − 62G>T]. Prostate cancer cases (n = 1320) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were frequency matched to controls (n = 1842), by age, race, time since initial screening and year of blood draw. An antioxidant score [range 3–12; low (3–7) versus high (8–12)] was created by summing the quartile levels of vitamin E, β-carotene and lycopene, which were coded from 1 to 4, respectively. The global tests for all eight single-nucleotide polymorphisms (SNPs) (excluding NOS2A −2892T>C, with low minor allele frequency) were statistically significant for prostate cancer (P = 0.005), especially for aggressive cancer (stage III–IV or Gleason score ≥ 7) (P = 0.01). The NOS2A IVS16 + 88 GT/TT was associated with increased prostate caner risk (odds ratio = 1.24, 95% confidence interval = 1.00–1.54), whereas the IVS20 + 524 AG/GG was associated with decreased risk (0.77, 0.66–0.90). The NOS3 IVS7 − 26GG was associated with increased prostate caner risk (1.33, 1.07–1.64). All these SNPs showed significant associations with aggressive cancer and not for non-aggressive cancer. In the evaluation of effect modification, the effect of the NOS2A IVS16 + 88 GT/TT on aggressive cancer was stronger among subjects with higher antioxidant intake (1.61, 1.18–2.19; Pinteraction = 0.01). Our results suggest that NOS gene polymorphisms are genetic susceptibility factors for aggressive prostate cancer.
doi:10.1093/carcin/bgp028
PMCID: PMC2664454  PMID: 19168583
13.  Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk 
Leukemia research  2008;33(2):250-258.
We conducted a case–control study to evaluate the association between paternal smoking and childhood leukemia and to evaluate potential modification by polymorphisms in CYP1A1. Histologically confirmed childhood leukemia cases (n = 164) and non-cancer controls (n = 164) were recruited from three teaching hospitals in Seoul, Korea. Five single nucleotide polymorphisms in CYP1A1 (–17961T>C, –9893G>A, I462V, 1188C>T (*2A), and 11599C>G) were genotyped and haplotypes were estimated by the expectation-maximization method. We also conducted a meta-analysis of 12 studies that have reported the association between paternal smoking and childhood leukemia risk. Paternal smoking at home was associated with all leukemias (OR = 1.8, 95% CI = 1.1–2.8) and acute lymphoblastic leukemia (ALL) (2.0, 1.2–3.4). An increasing trend in risk was observed for pack-years smoked after birth (Ptrend = 0.06 and 0.02, respectively) and the number of smokers in the home during the child's life (Ptrend = 0.05 and 0.03, respectively). Among those without the CGACC haplotype, ALL risk was significantly increased by the father's smoking at home (2.8, 1.5–5.3) and the presence of at least one smoker in the home (2.3, 1.2–4.4), and the test for interaction was significant (Pinteraction = 0.03 and 0.02, respectively). The meta-analysis showed that overall paternal smoking (1.13, 1.04–1.24) and smoking before the pregnancy of the child (1.12, 1.04–1.21) were significantly associated with childhood leukemia risk. Our results suggest that paternal smoking is a risk factor for childhood leukemia and the effect may be modified by CYP1A1 genotype.
doi:10.1016/j.leukres.2008.06.031
PMCID: PMC2787091  PMID: 18691756
Childhood leukemia; Paternal smoking; CYP1A1; Interaction; Haplotype
14.  Association of paternal age at birth and the risk of breast cancer in offspring: a case control study 
BMC Cancer  2005;5:143.
Background
Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea.
Methods
Histologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration.
Results
The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998).
Conclusion
These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.
doi:10.1186/1471-2407-5-143
PMCID: PMC1291359  PMID: 16259637
15.  Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia 
Hosgood, H. Dean | Wang, Wen-Chang | Hong, Yun-Chul | Wang, Jiu-Cun | Chen, Kexin | Chang, I-Shou | Chen, Chien-Jen | Lu, Daru | Yin, Zhihua | Wu, Chen | Zheng, Wei | Qian, Biyun | Park, Jae Yong | Kim, Yeul Hong | Chatterjee, Nilanjan | Chen, Ying | Chang, Gee-Chen | Hsiao, Chin-Fu | Yeager, Meredith | Tsai, Ying-Huang | Wei, Hu | Kim, Young Tae | Wu, Wei | Zhao, Zhenhong | Chow, Wong-Ho | Zhu, Xiaoling | Lo, Yen-Li | Sung, Sook Whan | Chen, Kuan-Yu | Yuenger, Jeff | Kim, Joo Hyun | Huang, Liming | Chen, Ying-Hsiang | Gao, Yu-Tang | Kim, Jin Hee | Huang, Ming-Shyan | Jung, Tae Hoon | Caporaso, Neil | Zhao, Xueying | Huan, Zhang | Yu, Dianke | Kim, Chang Ho | Su, Wu-Chou | Shu, Xiao-Ou | Kim, In-San | Bassig, Bryan | Chen, Yuh-Min | Cha, Sung Ick | Tan, Wen | Chen, Hongyan | Yang, Tsung-Ying | Sung, Jae Sook | Wang, Chih-Liang | Li, Xuelian | Park, Kyong Hwa | Yu, Chong-Jen | Ryu, Jeong-Seon | Xiang, Yongbing | Hutchinson, Amy | Kim, Jun Suk | Cai, Qiuyin | Landi, Maria Teresa | Lee, Kyoung-Mu | Hung, Jen-Yu | Park, Ju-Yeon | Tucker, Margaret | Lin, Chien-Chung | Ren, Yangwu | Perng, Reury-Perng | Chen, Chih-Yi | Jin, Li | Chen, Kun-Chieh | Li, Yao-Jen | Chiu, Yu-Fang | Tsai, Fang-Yu | Yang, Pan-Chyr | Fraumeni, Joseph F. | Seow, Adeline | Lin, Dongxin | Zhou, Baosen | Chanock, Stephen | Hsiung, Chao Agnes | Rothman, Nathaniel | Lan, Qing
Human genetics  2012;131(7):10.1007/s00439-012-1144-8.
A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10−12); however, this association did not achieve genome-wide significance (p < 10−7) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10−8; allelic risk = 0.80, 95% confidence interval (CI) = 0.74–0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67–0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
doi:10.1007/s00439-012-1144-8
PMCID: PMC3875137  PMID: 22367405

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