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Breast Cancer Genes

 Genes associated with breast cancer

 

According to the “Center of Disease Control and Prevention (CDC)” breast cancer is the most common cancer among American women. The incidence of breast cancer is rising worldwide. More recently an increase in aggressive neoplasias in young women has been observed worldwide.

A neoplasm is an abnormal growth of specific tissue cells. The term neoplasm refers to any abnormal new growth of tissue. This type of tissue grows by cellular proliferation more rapidly than normal. It continues to grow after the stimuli that initiated the new growth has passed. The newly growing tissue shows partial or complete lack of structural organization and functional coordination with the normal tissue. Often, it forms a distinct mass of tissue which can be either benign or malignant.

The cause of cancer is an abnormal mutational change in the genome. Several mutations can generate oncogenes with dominant gain of function and tumor suppressor genes with recessive loss of function. The accumulation of genetic mutations in genes involved in DNA repair and genes that control cell growth are known to cause cancer. The result is that cells carrying the mutations can grow and divide uncontrollably to form a tumor.

In breast cancer, certain cells in the breast tissue become abnormal and start multiplying without control or start forming a tumor. The most common form of this cancer begins in cells lining the milk ducts carrying milk to the nipple. This cancer type is also called ductal cancer. Other breast cancer forms can start in the milk producing glands, called lobular cancer, or even in other parts of the breast. Different variations or mutations of the BRCA1, BRCA2, CDH1, STK11, and TP53 genes are known to increase the risk of developing breast cancer. However, other genes such as AR, ATM, BARD1, CHEK2, DIRAS#, ERBB@, NBN, PALB2, RAD50, and RAD51 genes are also associated with breast cancer.

 

Many known risk breast cancer susceptibility alleles have now been genotyped in a large series of female BRCA1 and BRCA2 mutation carriers assembled by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) to evaluate their associations with risk of breast cancer for mutation carriers.

 

Mulligan et al. reported that of the 12 SNPs (rs2981582 in FGFR2, rs3803662 in TOX3/TNRC9, rs889312 in MAP3K1, rs13281615 at 8q24, rs381798 in LSP1, rs13387042 at 2q35, rs4973768 in SLC4A7/NEK10, rs10941679 at 5p12, rs6504950 in STXBP4/COX11, rs999737/rs10483813 in RAD51L1, rs2046210 at 6q25.1 and rs11249433 at 1p11.2) investigated so far, eight were associated with breast cancer risk for BRCA2 carriers (all but SNPs at 8q24, RAD51L1, 6q25.1 and STXBP4/COX11), whereas only three SNPs (6q25.1, TOX3/TNRC9 and 2q35) were associated with risk for BRCA1 mutation carriers.

 

We now know that a buildup of mutations in critical genes is the cause of cancer. Critical genes are those that control cell growth and division or the repair of damaged DNA. These mutations allow cancer cells to grow and divide uncontrollably and to form tumors. In general, genetic changes are acquired only in certain cells during a person's lifetime. These acquired genetic changes are called somatic mutations and are not inherited. In a smaller population, some inherited gene mutations increase the risk of developing cancer. However, to develop cancer additional mutations in other genes must occur. The following tables contain a list of known genes associated with breast cancer.

High-Risk Genes

 

#

Gene

Associated  cancers and risks

1

BRCAl

 

Female breast (57-84%), ovarian (24-54%), prostate (16-20%), male breast (4%), pancreatic (3%), melanoma, fallopian tube, primary peritoneal, endometrial (serous)

2

BRCA2

 

Female breast (41-84%), ovarian (11-27%), prostate (20-34%), pancreatic (5-7%), male breast (4-7%), melanoma, fallopian tube, primary peritoneal, endometrial (serous)

3

CDHl

 

Female breast (39-52%), diffuse gastric cancer (40-83%), colon

 

4

EPCAM

MLHl

MSH2

MSH6

PMS2

Ovarian (4-24%), colorectal (20-80%), endometrial (12-60%), stomach, pancreatic, biliary tract, urinary tract. small bowel, brain, sebaceous neoplasms

 

5

PTEN

 

Female breast (25-50%). thyroid (10%), endometrial (5-10%), colon, renal, melanoma

6

STKll

 

Female breast (32-54%), ovarian tumors (21%), colorectal (39%), pancreatic (11-36%), gastric (30%), lung (15%), small intestine (13%), cervical (10%), endometrial (10%), testicular tumors (9%)

7

TP53

 

Female breast. ovarian, soft tissue sarcoma, osteosarcoma, brain tumors, adrenocortical c'arcinoma; overall risk for cancer: nearly 100% in females, 73% in males

 

Moderate Risk Genes

 

#

Gene

Associated  cancers and risks

1

ATM

Female breast. colon, pancreatic

2

CHEK2

 

Female breast. male breast. colon, prostate, thyroid, renal, endometrial (serous), ovarian

3

PALB2

Female breast. male breast. pancreatic, ovarian

 

Newer Genes

 

#

Gene

Associated  cancers and risks

1

BARDl

Female breast. ovarian

2

BRIPl

Female breast. ovarian

3

FANCC

Female breast

3

NBN

Female breast. melanoma, non-Hodgkin lymphoma

4

RAD51C

Female breast. ovarian

5

RAD51D

Female breast. ovarian

6

XRCC2

Female breast. colon, pancreatic

 


Selected references


http://ghr.nlm.nih.gov/condition/breast-cancer


http://www.cancer.gov/


Mulligan et al., 2011; Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2. Mulligan et al. Breast Cancer Research 2011, 13:R110. http://breast-cancer-research.com/content/13/6/R110.


Dorothy Teegarden
Isabelle Romieu, and Sophie A. Lelièvre; Redefining the impact of nutrition on breast cancer incidence: is epigenetics involved? Nutr Res Rev. 2012 June ; 25(1): 68–95. doi:10.1017/S0954422411000199.