Parkinson's Disease Genes Do Not Segregate with Breast Cancer Genes' Loci

Published OnlineFirst June 13, 2013; DOI: 10.1158/1055-9965.EPI-13-0472

Cancer Epidemiology, Null Results in Brief Biomarkers & Prevention

Efrat Kravitz1,2, Yael Laitman3, Sharon Hassin-Baer1,4, Rivka Inzelberg1,2,4, and Eitan Friedman3,4

Abstract Background: Breast cancer and skin cancer rates among patients with Parkinson’s disease are higher than in non-Parkinson’s disease cases, and Jewish-Ashkenazi LRRK2G2019S mutation carriers have higher breast cancer rates than noncarriers. Because additional Parkinson’s disease predisposition genes are implicated in the malignant transformation process, we hypothesized that the association between breast cancer and Parkinson’s disease may be related to segregation of breast cancer loci with known Parkinson’s disease predisposition loci. Methods: Data mining for single-nucleotide polymorphisms (SNP), reportedly associated with breast cancer in genome-wide association study (GWAS) that localize to chromosomes bearing known Parkinson’s disease predisposition loci: PARK7, PINK1 (chromosome 1); SNCA (chromosome 4); PARK2 (chromosome 6); and LRRK2 (chromosome 12), was carried out. Results: A total of 188 breast cancer–associated SNPs were identiﬁed in 29 eligible manuscripts: 43 SNPs on chromosome 1 (PINK1), 46 SNPs on chromosome 4 (SNCA), 72 SNPs on chromosome 6 (PARK2), and 27 SNPs on chromosome 12 (LRRK2). No breast cancer–associated SNP was located at distance less than 500,000 bp from any of the analyzed Parkinson’s disease predisposition genes. Conclusions: The association between breast cancer and the most common genetic-inherited forms of Parkinson’s disease cannot be accounted for by allele cosegregation at the genomic level. Impact: To elucidate the association between Parkinson’s disease and breast cancer, a comprehensive approach that spans beyond a simple genetic association is required. Cancer Epidemiol Biomarkers Prev; 22(8); 1464–72. 2013 AACR.

Introduction cancer predisposition through genome-wide association Breast cancer is more frequently diagnosed in patients studies (GWAS) and assessed if they are overrepresented with sporadic (1) and inherited forms (2) of Parkinson’s in chromosomal regions associated with inherited forms disease than in the general population, yet the molecular of Parkinson’s disease. basis for this association remains elusive. Given the Materials and Methods involvement of Parkinson’s disease predisposition genes in cell cycle, their reported functions as oncogenes and Search procedure tumor suppressor genes (3), and somatic involvement in Database searches were carried out in PubMed (5), breast cancer tumorigenesis (e.g., ref. 4), we hypothesized GWAS catalog of the National Human Genome Research that the Parkinson’s disease–breast cancer association Institute (6), and the publication database of the Breast may be attributed to cosegregation and in linkage dis- Cancer Association Consortium (7) to identify GWAS equilibrium of breast cancer and Parkinson’s disease studies published until July 2012. predisposition genes. To test this notion, we conducted a focused literature search for single-nucleotide poly- Inherited Parkinson’s disease genes and morphisms (SNP) that have been associated with breast chromosomal loci The following Parkinson’s disease predisposition loci were targeted: (i) PARK7 (OMIM# 602533), chromosome Authors' Afﬁliations: 1The Parkinson Disease and Movement Disorders Clinic, and Department of Neurology; 2The Joseph Sagol Neuroscience 1p36.23; (ii) PINK1 (OMIM# 608309), chromosome 1p36.12; Center; 3The Susanne-Levy Gertner Oncogenetics Unit, The Institute of (iii) SNCA (OMIM# 163890), chromosome 4q22.1; (iv) Human Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan; and PARK2 4The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (OMIM# 602544), chromosome 6q25.2–q27; and (v) LRRK2 (OMIM# 609007); chromosome 12q12. Corresponding Author: Eitan Friedman, The Susanne-Levy Gertner Oncogenetics Unit, The Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel. Phone: 972-3- Selection criteria and SNPs 5303173; Fax: 972-3-535-7308; E-mail: [email protected] We searched peer-reviewed, English language publica- doi: 10.1158/1055-9965.EPI-13-0472 tions reporting GWAS analyses on all pathologic types 2013 American Association for Cancer Research. of breast cancer cases and controls of all ethnicities.

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Table 1. Articles included in this review

Populationa GWAS Article ref. Title Ethnicity Casesb Controlsb 13 Common variants at 12p11, 12q24, 9p21, Varied 10,200 9,531 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers 14 Genome-wide association analysis European, Asian 70,000 68,000 identifies three new breast cancer susceptibility loci 15 Genome-wide association study in East East-Asian 19,091 20,606 Asians identifies novel susceptibility (Chinese, Korean, Loci for breast cancer and Japanese) 16 Novel breast cancer susceptibility locus Varied (European, 11,880 12,487 at 9q31.2: results of a genome-wide West African, and association study East Asian) 17 Replication of breast cancer GWAS African American 316 7,484 susceptibility loci in the Women's Health Initiative African American SHARe Study 18 A combined analysis of genome-wide European 2,702 5,726 association studies in breast cancer 19 Replication of genome-wide discovered Cypriot 1,109 1,177 breast cancer risk loci in the Cypriot population 20 Potential novel candidate polymorphisms Canadian 1,501 1,563 identified in genome-wide association (predominantly study for breast cancer susceptibility Caucasian) 21 Common breast cancer susceptibility loci Caucasian 2,980 4,978 are associated with triple-negative breast cancer 22 A locus on 19p13 modifies risk of breast North American, 1,193 1,190 cancer in BRCA1 mutation carriers and European and is associated with hormone receptor- Australian negative breast cancer in the general population 23 Common genetic variants and European 2,680 2,546 modification of penetrance of BRCA2- associated breast cancer 24 Identification of a functional genetic Chinese, Japanese 12,671 10,339 variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium 25 Ancestry-shift refinement mapping of Asian, European, 10,176 13,286 the C6orf97-ESR1 breast cancer and African susceptibility locus 26 Genome-wide association study European 16,235 17,120 identifies five new breast cancer susceptibility loci 27 Evidence for SMAD3 as a modifier of North American, 4,035 3,382 breast cancer risk in BRCA2 mutation European and carriers Australian (Continued on the following page)

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Table 1. Articles included in this review (Cont'd )

Populationa GWAS Article ref. Title Ethnicity Casesb Controlsb 28 Common variants associated with breast Caucasian 3,030 2,427 cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers 29 Newly discovered breast cancer Predominantly 4,380 4,280 susceptibility loci on 3p24 and 17q23.2 European 30 Association of ESR1 gene tagging SNPs European >25,000 >25,000 with breast cancer risk 31 Common genetic variation in candidate Predominantly 4,470 4,560 genes and susceptibility to subtypes of Caucasian breast cancer 32 A risk variant in an miR-125b binding site Predominantly 455 1,142 in BMPR1B is associated with breast Caucasian cancer pathogenesis 33 A multistage genome-wide association European 9,770 10,799 study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1) 34 Genome-wide association study Chinese 6,531 3,998 identifies a new breast cancer susceptibility locus at 6q25.1 35 Genome-wide association study provides Ashkenazi Jews 1,442 1,465 evidence for a breast cancer risk locus at 6q22.33 36 A common coding variant in CASP8 is Predominantly 11,391–18,290 14,753–22,670 associated with breast cancer risk European, Asian 37 Genome-wide association study European, Asian 26,258 26,894 identifies novel breast cancer susceptibility loci 38 Genetic variation in TNF and Caucasian 5,546 5,219 lymphotoxin-alpha (TNF-LTA) and breast cancer risk 39 A genome-wide association study Predominantly 2,921 3,214 identifies alleles in FGFR2 associated Caucasian with risk of sporadic postmenopausal breast cancer 40 Common variants on chromosomes 2q35 European, 4,554 17,577 and 16q12 confer susceptibility to multiethnic estrogen receptor-positive breast cancer 41 Commonly studied single-nucleotide Predominantly >20,000 >20,000 polymorphisms and breast cancer: European, Asian results from the Breast Cancer Association Consortium

aPopulation of the entire study, including all stages/population sets. bNumber of cases/controls for all population sets.

Publications assessing interactions between SNPs and from GWAS replication stage with SNPs showing P 0.05 other risk factors or breast cancer mortality risk, and that localize to one of the 4 chromosomes of interest were candidate gene-based studies were excluded. Only results considered. After removal of duplicates, SNPs located to

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Table 2. Breast cancer–associated SNPs on chromosomes of interest

Chromosomal Chr Gene/regiona SNP positionb Pc 1 RIZ1 rs2235515 14,141,344 0.0204 1 ALPL rs3200254 21,894,735 0.038 1 ALPL rs3738097 21,894,816 0.036 1 WNT4 rs2473253 22,538,787 0.023 1 TRIT1 rs17570439 40,324,210 <0.0001 1 MYCL1 rs3134615 40,362,066 <0.0001 1 MAST2 rs4660891 46,319,447 0.004 1 PIK3R3 rs785467 46,521,559 0.019 1 GNG12 rs3766265 68,198,152 <0.0002 1 GNG12 rs3766270 68,215,424 <0.0005 1 DPYD rs12133176 97,706,237 0.0284 1 DPYD rs4950025 97,717,279 0.0121 1 DPYD rs528455 97,749,198 0.0442 1 DPYD rs10875071 97,814,678 0.0013 1 DPYD rs11165845 97,819,405 0.0273 1 DPYD rs12566907 97,862,237 0.0051 1 DPYD rs7548189 97,867,713 <0.0005 1 DPYD rs4434871 97,873,007 0.0066 1 DPYD rs4497250 97,882,933 0.0174 1 DPYD rs4379706 98,322,379 0.0418 1 DPYD rs6677116 98,337,283 0.0409 1 DPYD rs1801265 98,348,885 0.0493 1 COL11A1 rs1451036 103,149,593 0.0082 1 VAV3 rs2494059 108,239,958 0.0448 1 VAV3 rs1332684 108,414,230 0.0469 1 TRIM45 rs1048635 117,654,858 0.0013 1 rs11249433 121,280,613 <0.0001 1 IL6R rs1386821 154,382,049 0.019 1 ARHGEF2 rs1889532 155,951,502 0.032 1 CD1A rs411089 158,224,825 0.0452 1 CD1C rs10797006 158,257,838 0.0286 1 TBX19 rs2075976 168,269,338 0.0565 1 CACNA1E rs3820260 181,638,511 <0.0001 1 PLA2G4A rs6683363 186,927,369 0.0274 1 CR1 rs650877 207,748,793 0.0192 1 CR1 rs11118131 207,761,196 0.0221 1 CR1 rs677066 207,773,991 0.0036 1 CR1 rs6691117 207,782,931 0.0039 1 CR1 rs12034383 207,803,595 0.002 1 rs4546928 222,079,537 0.0095 1 ENAH rs3795443 225,675,003 0.0354 1 ENAH rs4653643 225,675,459 0.0063 1 ENAH rs2840967 225,824,028 0.008

1 PARK7 Range: 8,021,714–8,045,342 Strand: plus 1 PINK1 Range: 20,959,948–20,978,004 Strand: plus

4 TACC3 Rs1374468 1,724,579 0.04 4 ACOX3 Rs747580 8,373,088 0.0321 (Continued on the following page)

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Table 2. Breast cancer–associated SNPs on chromosomes of interest (Cont'd )

Chromosomal Chr Gene/regiona SNP positionb Pc 4 ACOX3 Rs2631731 8,429,817 0.0207 4 Rs2222309 12,691,840 0.0123 4 LDB2 Rs6837118 16,729,576 0.049 4 Rs2697705 17,418,921 <0.0001 4 KCNIP4 Rs1460475 21,565,822 0.02 4 Rs10025483 24,454,338 0.0122 4 Rs9884706 32,632,087 <0.0005 4 Rs2166278 32,642,222 <0.0006 4 KIAA1239 Rs12505080 37,349,340 <0.0001 4 Rs7696175 38,820,986 <0.0001 4 SHISA3 Rs3109633 42,380,579 0.047 4 TEC Rs2352593 48,197,767 0.026 4 FRYL Rs6843340 48,619,937 0.0009 4 UGT2B4 Rs1389930 70,347,172 0.0488 4 UGT2A1 Rs6600793 70,477,984 0.006 4 STE Rs3775775 70,718,282 0.0182 4 STE Rs3736599 70,725,821 0.0053 4 HNRPDL Rs1559949 83,340,605 0.0165 4 HNRPDL Rs4285076 83,369,287 0.038 4 MAPK10 Rs4403040 87,038,481 <0.0009 4 BMPR1B Rs1970801 96,070,525 <0.0002 4 BMPR1B Rs1434536 96,075,965 <0.0002 4 BMPR1B Rs11097457 96,076,813 <0.0002 4 ADH1B Rs1042026 100,228,466 0.0253 4 ADH1C Rs698 100,260,789 0.0196 4 MANBA Rs2866413 103,557,077 0.05 4 MANBA Rs228611 103,561,709 0.0259 4 MANBA Rs228614 103,578,637 0.0085 4 MANBA Rs228617 103,580,788 0.0047 4 MANBA Rs227284 103,607,635 0.0227 4 MANBA Rs227368 103,611,845 0.0101 4 MANBA Rs223502 103,640,758 0.034 4 MANBA Rs223500 103,647,047 0.0248 4 Rs9761051 120,013,590 <0.0006 4 LOC644624 Rs1433211 124,763,465 0.014 4 Rs724950 128,342,120 <0.0001 4 Rs2862752 132,285,856 0.0134 4 NR3C2 Rs16998733 149,337,408 <0.0001 4 Rs6837016 155,890,241 0.0004 4 PDGFC Rs1816164 157,696,636 0.0475 4 Rs581849 159,981,640 0.0385 4 Rs2014078 160,019,492 0.0127 4 Rs11721955 160,046,565 0.011 4 DDX60L Rs13110927 169,299,528 <0.0001

4 SNCA Range: 90,645,250–90,759,447 Strand: minus

6 IRF4 Rs12203592 396,321 0.0017 6 Rs1265273 4,469,641 <0.0002 6 Rs9393089 9,095,364 0.0247 (Continued on the following page)

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Table 2. Breast cancer–associated SNPs on chromosomes of interest (Cont'd )

Chromosomal Chr Gene/regiona SNP positionb Pc 6 PHACTR1 Rs9473086 12,957,035 0.0047 6 TPMT Rs9367980 18,131,464 0.014 6 THEM2 Rs3777663 24,700,235 0.013 6 THEM2 Rs9356943 24,709,830 0.029 6 LOC134997 Rs9393597 24,973,108 <0.0001 6 LRRC16A Rs9467504 25,414,325 <0.0001 6 TNF Rs361525 31,543,101 0.008 6 LSM2 rs480092 31,764,899 0.0465 6 BAT8 rs535586 31,860,337 0.0138 6 HLA-DRA rs3129871 32,406,342 0.0147 6 HLA-DRA rs2395182 32,413,317 0.0155 6 TCP11 rs2057537 35,090,279 <0.0005 6 CDKN1A rs3176336 36,648,816 0.003 6 C6orf89 rs9380618 36,853,543 <0.0008 6 rs2799359 46,144,252 <0.0010 6 GFRAL rs12210212 55,202,199 0.019 6 HMGCLL1 rs4072373 55,317,936 0.029 6 rs9454109 67,947,988 0.0178 6 rs6919990 77,384,675 0.0019 6 rs3857481 87,124,569 <0.0001 6 QRSL1 rs12333016 107,099,191 <0.0004 6 CDC40 rs7761436 110,502,831 0.0163 6 FYN rs6914091 112,081,735 0.0077 6 ROS1 rs9401003 117,718,303 <0.0007 6 RNF146 rs2180341 127,600,630 <0.0001 6 RNF146 rs6569479 127,606,588 <0.0001 6 ECHDC1 rs6569480 127,621,748 <0.0001 6 ECHDC1 rs7776136 127,638,348 <0.0001 6 rs11759744 127,708,247 0.0608 6 THEMIS rs9491859 128,064,363 <0.0001 6 VNN2 rs12211125 133,065,049 0.0103 6 rs9485372 149,608,874 <0.0001 6 C6orf97 rs3757318 151,914,113 <0.0001 6 C6orf97 rs12662670 151,918,856 <0.0001 6 C6orf97 rs9383932 151,919,720 <0.0003 6 C6orf97 rs1038304 151,933,175 <0.0001 6 C6orf97 rs6929137 151,936,677 0.017 6 C6orf97 rs3734804 151,939,181 0.0014 6 C6orf97 rs3734805 151,939,350 <0.0001 6 C6orf97 rs6932260 151,939,560 <0.0008 6 C6orf97 rs9383589 151,940,260 <0.0001 6 C6orf97 rs10872676 151,943,977 0.0016 6 C6orf97-ESR1 rs12665607 151,946,629 <0.0001 6 C6orf97-ESR1 rs7752591 151,947,068 0.0003 6 C6orf97-ESR1 rs2046210 151,948,366 <0.0001 6 C6orf97-ESR1 rs9397435 151,951,220 <0.0001 6 rs6900157 151,954,127 <0.0001 6 C6orf97-ESR1 rs6930633 151,958,091 0.0504 6 C6orf97-ESR1 rs852003 151,962,202 <0.0002 6 C6orf97-ESR1 rs77275268 151,969,198 0.0074 6 C6orf97-ESR1 rs9383938 151,987,357 <0.0004 6 ESR1 rs3020314 152,270,672 <0.0001 (Continued on the following page)

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Table 2. Breast cancer–associated SNPs on chromosomes of interest (Cont'd )

Chromosomal Chr Gene/regiona SNP positionb Pc 6 ESR1 rs3020377 152,272,398 0.0043 6 ESR1 rs3020390 152,276,458 0.0046 6 ESR1 rs3020317 152,278,741 0.003 6 ESR1 rs3020394 152,279,213 0.0034 6 ESR1 rs3020396 152,279,878 0.0038 6 ESR1 rs3020400 152,282,546 0.0047 6 ESR1 rs3020401 152,283,044 0.0039 6 ESR1 rs1884051 152,283,279 0.0299 6 ESR1 rs1884054 152,291,566 0.0328 6 ESR1 rs9383951 152,295,613 <0.0001 6 ESR1 rs3020405 152,299,953 0.0077 6 ESR1 rs726282 152,302,654 0.0167 6 ESR1 rs3020407 152,307,261 0.0062 6 rs694975 153,189,269 0.034 6 TIAM2 rs9478620 155,513,482 0.0351 6 TIAM2 rs3749870 155,554,351 0.0362 6 SOD2 rs4880 160,113,872 0.056

6 PARK2 Range: 161,768,590–163,148,834 Strand: minus

12 FOXM1 rs2074985 2,978,254 0.034 12 PRMT8 rs10774156 3,664,704 0.0462 12 PRMT8 rs1029766 3,703,500 0.0017 12 FGF23 rs7961824 4,476,217 0.0387 12 MLF2 rs2302371 6,858,126 0.0494 12 CDKN1B rs34330 12,870,695 0.012 12 GRIN2B rs2284424 13,988,870 <0.0009 12 rs7313833 28,083,196 <0.0001 12 PTHLH rs10771399 28,155,080 <0.0001 12 FGD4 rs10771973 32,792,974 <0.0002 12 rs12304191 47,949,145 0.0334 12 OR6C74 rs4388990 55,641,295 0.0076 12 RASSF3 rs15958 65,091,314 0.016 12 TMTC2 rs17740709 83,423,340 <0.0001 12 MKRN5 rs1461282 88,186,449 0.0444 12 rs7310517 89,149,235 <0.0006 12 rs10507088 97,879,744 <0.0003 12 GLTP rs7966820 110,302,270 0.0004 12 rs10850145 113,944,129 <0.0001 12 rs1292011 115,836,522 <0.0001 12 rs7955262 116,206,962 <0.0001 12 KSR2 rs12425296 117,987,574 0.042 12 KSR2 rs4766886 118,345,121 0.047 12 CIT rs4766950 120,278,241 0.024 12 AACS rs7307700 125,588,197 0.002 12 rs6489171 127,882,841 <0.0001 12 rs11609565 132,093,024 0.047

12 LRRK2 Range: 40,618,813–40,763,087 Strand: plus aIf applicable. bActual position for SNP search on map. cSmallest P value of all appearances.

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the chromosomes of interest were plotted using the NCBI microRNAs (miR) may be involved in promoting the Sequence Viewer 2.23 tool (8). The distances between each expression of breast cancer-related genes and concom- of the genes of interest and the identified SNPs on the itantly, repress genes that are needed for normal dopa- same chromosome were calculated. minergic function. Indeed, miR-7, which represses a-synuclein protein levels and protects cells against Results oxidative stress, also inhibits epithelial-to-mesenchymal Of 194 articles identified, 153 articles did not meet the transition and metastasis of breast cancer cells via focal selection criteria, and 14 did not report any chromosomally adhesion kinase expression (10). Finally, the reported relevant SNP. The 29 articles that met all review criteria are association between breast cancer and Parkinson’s dis- listed in Table 1. Overall, 188 breast cancer-associated SNPs ease may relate to abnormal estrogen metabolism. located to one of the 4 "target chromosomes" were identi- Women have a reduced Parkinson’s disease risk com- fied (Table 2): 43 SNPs localize to chromosome 1 (minimal pared with age-matched men, a phenomenon attributed distance from PINK1 ¼ 916,731 bps; minimal distance from by some researchers to the neuroprotective properties of PARK7 ¼ 6,096,002 bps); 46 SNPs localize to chromosome 4 estrogen in Parkinson’s disease relevant neurons (11). (minimal distance from SNCA ¼ 3,606,769 bps); 72 SNPs Tamoxifen, a selective estrogen receptor (ER) modulator localize to chromosome 6 (minimal distance from PARK2 ¼ given to patients with ER-positive breast cancer, has 1,654,718 bps); 27 SNPs localize to chromosome 12 (min- been reported to increase Parkinson’s disease rates (12). imal distance from LRRK2 ¼ 7,186,058 bps). None of the Thus, in postmenopausal women, markedly reduced identified breast cancer-associated SNPs were located at estrogen synthesis may both increase the risk of Par- genomic distance less than 500,000 bps from any of the kinson’s disease and promote the expression of ER analyzed Parkinson’s disease genes. genes in breast tissue to enhance breast cancer risk. Noteworthy this is a viable speculation that should be Discussion viewed as such. No breast cancer-associated SNPs localized in the geno- In conclusion, the association between breast cancer mic proximity of Parkinson’s disease predisposition and the most common genetic forms of inherited Parkin- genes found on chromosomes 1, 4, 6, or 12. Thus, the son’s disease cannot be accounted for by allele cosegrega- observed increased breast cancer rates in inherited forms tion at the genomic level. of Parkinson’s disease cannot be accounted for by a simple cosegregation and shared genomic loci. Disclosure of Potential Conflicts of Interest Despite the lack of association at the genomic level No potential conflicts of interest were disclosed. between breast cancer SNPs and Parkinson’s disease predisposition genes, other genetic or epigenetic mechanisms Authors' Contributions may still be operative. If breast cancer results from the Conception and design: S.B. Hassin, R. Inzelberg, E. Friedman actions of multiple rare alleles, each one with a medium Development of methodology: E. Kravitz, Y. Laitman, R. Inzelberg, E. Friedman effect on breast cancer risk, then the methodology used in Acquisition of data (provided animals, acquired and managed GWAS would have missed these relatively rare sequence patients, provided facilities, etc.): E. Kravitz, Y. Laitman, S.B. Hassin Analysis and interpretation of data (e.g., statistical analysis, biosta- variants. This explanation seems less likely as there was no tistics, computational analysis): E. Kravitz, Y. Laitman, E. Friedman association reported between family history of breast can- Writing, review, and/or revision of the manuscript: E. Kravitz, S.B. cer and Parkinson’s disease risk in a large U.S. cohort (9). To Hassin, R. Inzelberg, E. Friedman Administrative, technical, or material support (i.e., reporting or orga- assess this possibility, a whole-exome, or even a whole- nizing data, constructing databases): E. Kravitz, Y. Laitman genome, dataset of breast cancer and Parkinson’s disease Study supervision: R. Inzelberg cases should be queried, when it becomes available. Another possible explanation for the breast cancer– Received May 5, 2013; revised May 16, 2013; accepted May 17, 2013; Parkinson’s disease association may be epigenetic: published OnlineFirst June 19, 2013.

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1472 Cancer Epidemiol Biomarkers Prev; 22(8) August 2013 Cancer Epidemiology, Biomarkers & Prevention

Parkinson's Disease Genes Do Not Segregate with Breast Cancer Genes' Loci

Efrat Kravitz, Yael Laitman, Sharon Hassin-Baer, et al.

Cancer Epidemiol Biomarkers Prev 2013;22:1464-1472. Published OnlineFirst June 13, 2013.

Updated version Access the most recent version of this article at: doi:10.1158/1055-9965.EPI-13-0472

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