Methods for identifying risk of breast cancer and treatments thereof

• US 20050272043A1
• Filed: 05/27/2004
• Published: 12/08/2005
• Est. Priority Date: 07/24/2003
• Status: Abandoned Application

• Current Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: Braun, Andreas, Hoyal-Wrightson, Carolyn R., Reneland, Rikard Henry, Roth, Richard B., Nelson, Matthew Roberts, Kammerer, Stefan M.
• Application Number:
  US10/857,780
• Publication Number:
  US 20050272043A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G01N 33/57415 of breast

Abstract

Provided herein are methods for identifying risk of breast cancer in a subject and/or a subject at risk of breast cancer, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for treating breast cancer, and therapeutic methods for treating breast cancer in a subject. These embodiments are based upon an analysis of polymorphic variations in nucleotide sequences within the human genome.

Claims

1. A method for identifying a subject at risk of breast cancer, which comprises detecting the presence or absence of a polymorphic variation associated with breast cancer corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO:

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs1018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs10132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908;

whereby the presence of the one or more polymorphic variations associated with breast cancer is indicative of the subject being at risk of breast cancer.

2. The method of claim 1, which further comprises obtaining the nucleic acid sample from the subject.

3. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of rs5030391, rs10402760, and rs710845.

4. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of position 30965 of SEQ ID NO:

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2 and position 39046 of SEQ ID NO;

2.

5. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of rs4630966, rs9827084, rs9864865, rs6804951 and rs6770548.

6. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO:

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396 and rs11278712.

7. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of rs2294495, position 15761 of SEQ ID NO:

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs018396, rs12044452, rs2982390, rs2502980, rs6697805 and rs10554242.

8. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs0132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, and rs10605948.

9. The method of claim 1, wherein a polymorphic variation is detected at one or more positions selected from the group consisting of rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974 and rs2895908.

10. The method of claim 1, wherein one or more polymorphic variations are detected at one or more positions in linkage disequilibrium with a polymorphic variation at one or more of the positions in claim 1.

11. The method of claim 1, wherein detecting the presence or absence of the one or more polymorphic variations comprises:

hybridizing an oligonucleotide to the nucleic acid sample, wherein the oligonucleotide is complementary to a nucleotide sequence in the nucleic acid and hybridizes to a region adjacent to the polymorphic variation;

extending the oligonucleotide in the presence of one or more nucleotides, yielding extension products; and

detecting the presence or absence of a polymorphic variation in the extension products.

12. The method of claim 1, wherein the subject is a human.

13. A method for identifying a polymorphic variation associated with breast cancer proximal to an incident polymorphic variation associated with breast cancer, which comprises:

identifying a polymorphic variation proximal to the incident polymorphic variation associated with breast cancer, wherein the incident polymorphic variation is at a position corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs0132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908; and

determining the presence or absence of an association of the proximal polymorphic variant with breast cancer.

14. The method of claim 13, wherein the proximal polymorphic variation is within a region between about 5 kb 5′

of the incident polymorphic variation and about 5 kb 3′

of the incident polymorphic variation.

15. The method of claim 13, which further comprises determining whether the proximal polymorphic variation is at a position in linkage disequilibrium with the incident polymorphic variation.

16. The method of claim 13, which further comprises identifying a second polymorphic variation proximal to the identified proximal polymorphic variation associated with breast cancer and determining if the second proximal polymorphic variation is associated with breast cancer.

17. The method of claim 16, wherein the second proximal polymorphic variant is within a region between about 5 kb 5′

of the incident polymorphic variation and about 5 kb 3′

of the proximal polymorphic variation associated with breast cancer.

18. An isolated nucleic acid which comprises one or more polymorphic variations corresponding to a variation selected from the group consisting of a thymine at position 45003 of SEQ ID NO:

1, an adenine at position 47504 of SEQ ID NO;

1, an adenine at position 30965 of SEQ ID NO;

2, a cytosine at position 38865 of SEQ ID NO;

2, a thymine at position 39035 of SEQ ID NO;

2, a cytosine at position 39046 of SEQ ID NO;

2, a cytosine at position 34941 in SEQ ID NO;

4, a guanine at position 35629 in SEQ ID NO;

4 and an adenine at position 15761 of SEQ ID NO;

5.

19. An oligonucleotide comprising a nucleotide sequence complementary to a portion of the nucleotide sequence of claim 18, wherein the 3′

end of the oligonucleotide is adjacent to a polymorphic variation.

20. A microarray comprising an isolated nucleic acid of claim 18 linked to a solid support.

21. A method of genotyping a nucleic acid which comprises determining the nucleotide at one or more positions corresponding to a position selected from the group consisting of position 45003 of SEQ ID NO:

1, position 47504 of SEQ ID NO;

1, position 30965 of SEQ ID NO;

2, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, position 34941 in SEQ ID NO;

4, position 35629 in SEQ ID NO;

4 and position 15761 of SEQ ID NO;

5 in a nucleic acid.

22. A method for identifying a candidate molecule that modulates cell proliferation, which comprises:

(a) introducing a test molecule to a system which comprises a nucleic acid comprising a nucleotide sequence selected from the group consisting of;

(i) a nucleotide sequence in SEQ ID NO;

1-17;

(ii) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;

1-17;

(iii) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;

1-17;

(iv) a fragment of a nucleotide sequence of (i), (ii), or (iii);

wherein the nucleotide sequence comprises a polymorphic variation associated with an increased risk of breast cancer corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs1018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs10132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908;

or

introducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv) and comprises a polymorphic variation associated with an increased risk of breast cancer; and

(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein,

whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate molecule that modulates cell proliferation.

23. The method of claim 22, wherein the system is an animal.

24. The method of claim 22, wherein the system is a cell.

25. A method for treating breast cancer in a subject, which comprises administering a candidate molecule identified by the method of claim 22 to a subject in need thereof, whereby the candidate molecule treats breast cancer in the subject.

26. A method for identifying a candidate therapeutic for treating breast cancer, which comprises:

(a) introducing a test molecule to a system which comprises a nucleic acid comprising a nucleotide sequence selected from the group consisting of;

(i) a nucleotide sequence in SEQ ID NO;

1-17;

(ii) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;

1-17;

(iii) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;

1-17;

(iv) a fragment of a nucleotide sequence of (i), (ii), or (iii);

wherein the nucleotide sequence comprises a polymorphic variation associated with an increased risk of breast cancer corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs1018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs10132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908;

or

introducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv) and comprises a polymorphic variation associated with an increased risk of breat cancer; and

(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein,

whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate therapeutic for treating breast cancer.

27. The method of claim 26, wherein the test molecule inhibits cell proliferation or cell metastasis.

28. A method for treating breast cancer in a subject, which comprises contacting one or more cells of a subject in need thereof with a nucleic acid, wherein the nucleic acid comprises a nucleotide sequence selected from the group consisting of:

(a) a nucleotide sequence in SEQ ID NO;

1-17;

(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;

1-17;

(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;

1-17;

(d) a fragment of a nucleotide sequence of (a), (b), or (c); and

(e) a nucleotide sequence complementary to the nucleotide sequences of (a), (b), (c), or (d);

wherein the nucleotide sequence comprises a polymorphic variation associated with an increased risk of breast cancer corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs1018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs0132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908;

whereby contacting the one or more cells of the subject with the nucleic acid treats breast cancer in the subject.

29. The method of claim 28, wherein the nucleic acid is RNA or PNA.

30. The method of claim 29, wherein the nucleic acid is duplex RNA.

31. The method of claim 30, wherein a strand of the RNA comprises a nucleotide sequence selected from the group consisting of ACAACCGGAAGGUGUAUGA (SEQ ID NO:

4928);

GCCAACCAAUGUGCUAUUC (SEQ ID NO;

     4929);

GAUCACCAUGGAGCCAAUU (SEQ ID NO;

4930;

CUGUCACUCGAGAUCUUGA (SEQ ID NO;

     4931);

GAGUUGGAUAGCAAGACAA (SEQ ID NO;

     4932) and CGUACGCGGAAUACUUCGA (SEQ ID NO;

4933.

32. A method for treating breast cancer in a subject, which comprises:

detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the one or more polymorphic variations are detected at a position corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs1018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs10132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908; and

administering a breast cancer treatment to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample.

33. The method of claim 32, wherein the breast cancer treatment comprises a nucleic acid comprising a nucleotide sequence complementary to a nucleotide sequence in SEQ ID NO:

1-17.

34. The method of claim 33, wherein the nucleic acid is a double stranded RNA.

35. The method of claim 34, wherein a strand of the RNA comprises a nucleotide sequence selected from the group consisting of ACAACCGGAAGGUGUAUGA (SEQ ID NO:

4928);

GCCAACCAAUGUGCUAUUC (SEQ ID NO;

     4929);

GAUCACCAUGGAGCCAAUU (SEQ ID NO;

     4930);

CUGUCACUCGAGAUCUUGA (SEQ ID NO;

     4931);

GAGUUGGAUAGCAAGACAA (SEQ ID NO;

     4932) and CGUACGCGGAAUACUUCGA (SEQ ID NO;

     4933).

36. The method of claim 32, which further comprises extracting and analyzing a tissue biopsy sample from the subject.

37. The method of claim 32, wherein the treatment is chemotherapy, surgery, radiation therapy, and combinations of the foregoing.

38. The method of claim 37, wherein the chemotherapy is selected from the group consisting of cyclophosphamide (Cytoxan), methotrexate (Amethopterin, Mexate, Folex), fluorouracil (Fluorouracil, 5-Fu, Adrucil), cyclophosphamide, doxorubicin (Adriamycin), and combinations of the foregoing.

39. The method of claim 38, wherein the combinations are selected from the group consisting of cyclophosphamide (Cytoxan), methotrexate (Amethopterin, Mexate, Folex), and fluorouracil (Fluorouracil, 5-Fu, Adrucil);

cyclophosphamide, doxorubicin (Adriamycin), and fluorouracil; and

doxorubicin and cyclophosphamide.

40. The method of claim 32, wherein the breast cancer treatment reduces breast cancer metastasis.

41. A method for detecting or preventing breast cancer in a subject, which comprises:

detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the polymorphic variation is detected at a position corresponding to a position selected from the group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs0132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908; and

administering a breast cancer prevention procedure or detection procedure to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample.

42. The method of claim 41, wherein the breast cancer detection procedure is selected from the group consisting of a mammography, an early mammography program, a frequent mammography program, a biopsy procedure, a breast biopsy and biopsy from another tissue, a breast ultrasound and optionally ultrasound analysis of another tissue, breast magnetic resonance imaging (MRI) and optionally MRI analysis of another tissue, electrical impedance (T-scan) analysis of breast and optionally of another tissue, ductal lavage, nuclear medicine analysis (e.g., scintimammography), BRCA1 and/or BRCA2 sequence analysis results, thermal imaging of the breast and optionally of another tissue, and a combination of the foregoing.

43. The method of claim 41, wherein the breast cancer prevention procedure is selected from the group consisting of one or more selective hormone receptor modulators, one or more compositions that prevent production of hormones, one or more hormonal treatments, one or more biologic response modifiers, surgery, and drugs that delay or halt metastasis.

44. The method of claim 43, wherein the selective hormone receptor modulator is selected from the group consisting of tamoxifen, reloxifene, and toremifene;

the composition that prevents production of hormones is an aramotase inhibitor selected from the group consisting of exemestane, letrozole, anastrozol, groserelin, and megestrol;

the hormonal treatment is selected from the group consisting of goserelin acetate and fulvestrant;

the biologic response modifier is an antibody that specifically binds herceptin/HER2;

the surgery is selected from the group consisting of lumpectomy and mastectomy; and

the drug that delays or halts metastasis is pamidronate disodium.

45. A composition comprising a breast cancer cell and an antibody that specifically binds to a protein, polypeptide or peptide encoded by a nucleotide sequence identical to or 90% or more identical to a nucleotide sequence in SEQ ID NO:

1-17, wherein the protein, polypeptide or peptide comprises a leucine corresponding to the amino acid at position 359 in SEQ ID NO;

23, a leucine corresponding to the amino acid at position 378 in SEQ ID NO;

23, an alanine corresponding to the amino acid at position 857 in SEQ ID NO;

23, an alanine corresponding to the amino acid at position 902 in SEQ ID NO;

23, a proline corresponding to the amino acid at position 352 in SEQ ID NO;

20, an alanine corresponding to the amino acid at position 348 in SEQ ID NO;

20 or a glycine corresponding to the amino acid at position 794 in SEQ ID NO;

24.

46. A composition comprising a breast cancer cell and a RNA, DNA, PNA or ribozyme molecule comprising a nucleotide sequence identical to or 90% or more identical to a portion of a nucleotide sequence in SEQ ID NO:

1-17, or a complementary sequence thereof, wherein the nucleotide sequence comprises a polymorphic variation associated with an increased risk of breast cancer corresponding to a position selected from the group consisting of group consisting of rs5030391, rs10402760, rs710845, position 30965 of SEQ ID NO;

2, rs3775168, position 38865 of SEQ ID NO;

2, position 39035 of SEQ ID NO;

2, position 39046 of SEQ ID NO;

2, rs4630966, rs9827084, rs9864865, rs6804951, rs6770548, rs7949480, rs7121260, rs7128317, rs2276385, rs2276383, rs1892921, rs1541306, rs3814721, rs1892919, rs2852365, rs3750913, position 34941 in SEQ ID NO;

4, rs949325, position 35629 in SEQ ID NO;

4, rs2298456, rs1573500, rs4945411, rs10128658, rs2298457, rs3838779, rs10898814, rs7930142, rs7930544, rs7930722, rs1939247, rs1939243, rs4245463, rs4944258, rs7926751, rs1573502, rs7127865, rs1894003, rs4945430, rs1939242, rs10793016, rs4945434, rs678193, rs560777, rs676721, rs585228, rs675185, rs5792574, rs2511075, rs541022, rs1791544, rs642618, rs552966, rs607446, rs3018302, rs3018301, rs2511114, rs548961, rs579320, rs495567, rs493065, rs610004, rs610041, rs673478, rs670802, rs2511116, rs615000, rs482013, rs2511079, rs2250866, rs2508858, rs2276396, rs11278712, rs2294495, position 15761 of SEQ ID NO;

5, rs8179467, rs11591202, rs12034848, rs3831910, rs4237, rs2232982, rs12041159, rs2076343, rs1018396, rs12044452, rs2982390, rs2502980, rs6697805, rs10554242, rs3327, rs2526926, rs2526914, rs2526913, rs2526921, rs7159986, rs2332916, rs10132242, rs11627663, rs4899441, rs7148199, rs1990437, rs8004210, rs8019653, rs12232220, rs4899442, rs2332917, rs8015749, rs12437188, rs12432148, rs4378563, rs740978, rs740976, rs4903059, rs4903060, rs9635259, rs2052142, rs758913, rs747987, rs11423372, rs5809592, rs8007348, rs4899445, rs4903062, rs1990440, rs4479167, rs4606655, rs4606656, rs4489943, rs8007559, rs8006156, rs12431400, rs12431384, rs12433097, rs12433184, rs2877821, rs4569195, rs11628905, rs2191822, rs12433603, rs11448438, rs8009692, rs4265749, rs4307892, rs12431975, rs4903071, rs1860749, rs1860748, rs8010957, rs6420906, rs12434800, rs7142579, rs8010875, rs8004767, rs4899449, rs10605948, rs12437080, rs12431943, rs1054745, rs8019453, rs12431547, rs1959029, rs1959028, rs8013347, rs2235972, rs2235973, rs2235974, and rs2895908.

47. The composition of claim 46, wherein the RNA molecule is a short inhibitory RNA molecule.