top of page

Home  >  For Participants  >  Study Findings  >  Genetics



Below are common terms used in genetic studies:

Allele: Pairs or series of genes on a chromosome that determine hereditary characteristics.

Chromosome: A thread-like structure of nucleic acids and proteins that carries genetic information in the form of genes. Humans have 23 pairs of chromosomes.

Genome-wide association study (GWAS): A study to identify if inherited genetic variants are associated with risk of a certain disease.

Locus: The position of a gene or gene marker on a chromosome.

Single nucleotide polymorphism (SNP): A variation in a single DNA building block, also known as a nucleotide.

Susceptibility locus/loci: An allele that increases risk of a disease, but is not necessary or sufficient for disease expression.

Variant: An alteration in the most common DNA nucleotide sequence.

Breast Cancer

  • A 2012 study researched SNP rs2046210, which has previously been associated with increased risk of breast cancer in Asian women but the role of which is uncertain in European women. European studies have identified a different SNP, rs12662670, for this locus (6p25.1). This study found that SNP rs2046210 was associated with a greater risk of ER- than ER+ breast cancer in Europeans; in Asians, there was no clear leaning towards a specific ER receptor style. Each SNP was associated with risk after adjusting for the other SNP,  suggesting the presence of two variants at 6q25.1, each independently associated with breast cancer risk in Asians and in Europeans. The variant tagged by rs2046210 was associated with a greater risk of ER- tumors.  Read more here.

  • Researchers identified two novel susceptibility loci for breast cancer at chromosomes 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with increased risk of ER-negative breast cancer but showed a weaker association with overall breast cancer and no association with ER-positive breast cancer. SNP rs17530068 at 6q14 was associated with increased risk of overall breast cancer, ER-negative, and ER-positive breast cancer. Three loci previously associated with greater ER-negative (19p13) and both ER-negative and ER-positive breast cancer risk (6p25 and 12p11) were confirmed.  Read more here.

  • A 2013 genome-wide association study (GWAS) examined susceptibility loci specific to ER-negative breast cancer. This study identified SNPs at four loci that were associated with associated with ER-negative, but not ER-positive, breast cancer risk. These four loci were MDM4 and LGR6 at chromosomes 1q32.1, 2p24.1, and FTO at chromosome 16q12.2.  Read more here.

  • A 2013 study identified three independent risk signals within the 10q26 locus in the second intron of FGFR2, the locus shown to be most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. Researchers also identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation, a technique used to investigate the interaction between proteins and DNA in a cell, showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and E2F1 preferentially bound the risk variant of rs35054928.  Read more here.

  • A 2014 study found that while FGFR2 has been identified as a breast cancer susceptibility gene, other variations in fibroblast growth factor receptors (FGFR1, FGFR3, FGFR4, FGFRL1) were not associated with risk of breast cancer to the same degree. The strongest association besides FGFR2 was FGFR3 in European women, with an estimated per-allele odds ratio of 1.05, which was still much lower than observed for SNPs in FGFR2.  Read more here.

  • The 19p13.1 breast cancer susceptibility locus modifies breast cancer risk in BRCA1 mutation carriers and is also established to be associated with greater risk of ovarian cancer. A 2012 study found no evidence that 19p13.1 variants were associated with either overall breast cancer or ER-positive breast cancer; however, they were associated with greater risk of ER-negative breast cancer and triple negative (ER-, PR-, HER2-negative) at rs8170. Furthermore, once adjusted for triple negative breast cancer, rs8170 was no longer associated with ER-negative breast cancer risk, and a significant genome-wide association was found between rs8170 and triple negative breast cancer. These findings provide evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct pathways. Read more here.

  • Researchers have identified a new breast cancer susceptibility locus at chromosome 9q31.2: rs865686. A 2012 study found this susceptibility locus was inversely associated with breast cancer risk among women of European descent. The association was strongest for ER+ breast cancer, which lends further support to the theory that genetic susceptibility varies according to tumor subtype.  Read more here.

  • Using data from 50 case-control studies, researchers mapped the 2q35 breast cancer susceptibility locus using 1,560 genotyped and imputed single nucleotide polymorphisms (SNPs). They found that rs4442975 is associated with allele-specific FOXA1 binding, chromatin looping and IGFBP5 expression, suggesting that the g-allele of rs4442975 may increase breast cancer susceptibility through reduced IGFBP5 expression.  Read more here.

  • Genetic variations in the SNPs of microRNA (miRNA) or in the miRNA binding sites may affect the miRNA-dependent DNA expression/regulation. This could consequently affect many cancers, including breast cancer, and may alter individual risk to the disease. Combining nine genome-wide association studies, researchers found five miRNA binding site SNPs significantly associated with breast cancer risk. These SNPs are rs1045494, rs1052532, rs10719, rs4687554, and rs3134615, located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1 respectively.  Read more here.

  • A 2014 study did not find evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs (2.5 billion possible two SNP combinations) and the large sample size. Boolean operation-based screening and testing was used to evaluate each two SNP combination.  Read more here.

  • Genome-wide association studies have previously identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. Researchers genotyped 428 SNPs using data from the Breast Cancer Association Consortium to identify the most causal SNPs. A 2015 study identified four sets of iCHAV variants, three of which were located within ZNF365. The most strongly associated SNP, rs10995201 in iCHAV1, was linked with both decreased ER-positive and ER-negative breast cancer risk, and was associated with decreased percent mammographic density. iCHAV2 and iCHAV3 were associated with both ER-positive and ER-negative breast cancer, though iCHAV4, located 5’ of ADO, was associated with only ER-positive breast cancer. A haplotype in iCHAV2 was found to function as a silencer of an NRBF2 promoter, suggesting a role in the development of breast cancer.  Read more here.

  • Researchers analyzed genetic variants across 5q11.2, a chromosome known to have associations with breast cancer risk. The study revealed four cancer risk allele candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) that increased expression of the MAP3K1 gene, suggesting that MAP3K1 is the likely gene of focus in 5q11.2.  Read more here.

  • Researchers have previously identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. A 2015 study found that two independent association signals at 4q24 - variants rs62331150 and rs73838678 residing in the promoter of gene TET2 - are in linkage disequilibrium with rs9790517, meaning that sets of linked genes do not occur at the expected frequency. TET2 appears to play an important role in tumor suppression, and therefore these variants may be associated with breast cancer risk through their regulation of TET2 gene expression.  Read more here.

  • Previous studies have suggested that gene variations in CASP8 on chromosome 2 are associated with breast cancer risk. A 2015 genotyping study found an association between increased breast cancer risk and intron SNP rs1830298 in ALS2CR12for European subjects. Three additional independent breast cancer associations with other intron SNPs were also identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475).  Read more here.

  • Researchers created a polygenic risk score (PRS) that examined multiplicative interactions between 77 breast-cancer associated SNPs and derived absolute breast cancer risk from relative risk estimates and UK incidence and mortality rates. This study found that the risk of developing breast cancer for women in the highest 1% of the PRS was three times higher than the risk of women in the middle quintile of PRS.  Read more here.

  • A 2014 study identified 25 new loci associated with risk of triple-negative breast cancer.  Read more here

  • Variants in mitotic genes (genes directly involved in mitosis or in regulating its process) were investigated for association with breast cancer risk and grade of tumor tissue. While no SNPs were individually associated with high-grade cancer, which is more undifferentiated and often fatal, the gene TACC2 was identified as an area of interest. Analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk.  Read more here.

  • A 2015 genome wide association study found 15 new susceptibility loci for breast cancer. Likely genes of interest were identified in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1.  Read more here.

  • Single nucleotide polymorphisms (SNPs) rs676256, rs865686, rs10816625, and rs13294895 in chromosomes 9p31.2 were found to be associated with ER-positive breast cancer. These SNPs were also found to interact with known drivers of hormone driven breast cancer, including ER-α, FOXA1 and GATA-3. SNPs rs10816625 and rs13294895 appeared to have allele-specific effects on enhancer activity and could interact with the KLF4 gene locus.  Read more here.

  • A 2016 study identified TRM61B and WDR43 at chromosome 2p23.2 and PPIL3 at chromosome 2q33 as susceptibility loci for ER-negative breast cancer.  Read more here.

  • Researchers found that for women with a history of preeclampsia, the T allele of IGF1R variant rs2016347 was associated with a lower risk of breast cancer. This effect was most noticeable for HR+ breast cancer and in women whose age at first birth was younger than 30 years.  Read more here.

  • Previous research has identified SNP rs10771399 at chromosome 12p11 as associated with breast cancer risk. A 2016 fine-scale mapping study revealed four more independent association signals at 12p11(rs7297051, rs805510 and rs113824616, and rs1871152) among participants of European descent.  Read more here.

  • A 2017 study examined the relationship between exonic variation and many breast cancer subtypes (ER, PR, HER2). No new exonic variants were found to be statistically significantly associated with breast cancer risk.  Read more here.

  • A 2017 genome-wide association study identified 65 new loci associated with breast cancer risk among women of European and East Asian descent. Researchers used in silico data (computer simulation of cell behavior) to predict target genes in breast cells at each locus.  Read more here.

  • A 2017 study focused on susceptibility variants for ER-negative breast cancer among women of European origin and identified ten variants at nine new loci associated with ER- breast cancer risk.  Read more here.

  • A 2017 study qualified BRCA2 isoforms (functionally similar proteins with similar amino acid sequences) retaining or missing exon 3 and assessed the cancer risk associated with the BRCA2 c.68‐7T > A variant. Although exon 3 exclusion was 4.5 times higher among variant carriers than controls, researchers did not find evidence of increased risk of breast cancer when co-occurring with pathogenic variants. Results from the study suggest the nonpathogenicity of the BRCA2 c.68‐7T > A, meaning the variant is not likely associated with disease.  Read more here.

  • A 2018 transcriptome wide association study identified 48 genes associated with breast cancer risk, including 14 genes at loci not yet reported for breast cancer.  Read more here.

  • A 2019 study evaluated associations between germline variants and breast cancer-specific mortality. Researchers did not find any germline variants directly associated with breast cancer-specific mortality, even if there were variants on chromosome 7 close to genes for which there is evidence of breast cancer association.  Read more here.

  • A 2018 transcriptome wide association study identified 48 genes associated with breast cancer risk, including 14 genes at loci not yet reported for breast cancer.  Read more here.

  • A 2018 study found evidence that BRCA2 variant c.68-7T > A has no cancer causing properties.  Read more here.

  • A single nucleotide polymorphism (SNP) is a variation at a specific location within a DNA sequence. This 2016 study evaluated twelve SNPs of CASP8 and their association with all breast cancer, ER-positive, and HER2-positive breast cancers. Results from the study suggested rs2293554 was statistically significantly associated with HER2-positive breast cancer. Read more here.

  • Fanconi anemia (FA) is an inherited blood disorder caused by mutations in certain genes. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk. FANCC, the gene for FA type C, has been proposed as a potential breast cancer susceptibility gene. This research project genotyped two truncating FANCC variants and did not find evidence of an association with the risk of breast cancer. Read more here.

  • Researchers developed polygenic risk scores (PRS) that examined multiplicative interactions between breast-cancer associated SNPs. Goodness-of-fit tests indicated that the PRS were well calibrated and predicts disease risk accurately in the population. Read more here.

  • A 2019 study reported on a network-based GWAS to identify genetic determinants of breast cancer prognosis in a dataset of 84,457 breast cancer patients of European ancestry. By aggregating the survival estimates of multiple variants across genes and using a network propagation method, the researchers identified several biological processes that may mediate a germline genetic effect on breast cancer prognosis, including regulation of apoptosis, G-alpha signaling, and the circadian clock mechanism. Read more here.

  • Researchers explored 150 breast cancer risk regions by combining association analysis with in silico genomic feature annotations and defined 205 independent risk-associated signals with the set of credible causal variants in each one. Read more here.

  • This 2020 TWAS analysis used GTEx mammary tissue gene expression data and GWAS summary data from the largest meta‐analysis for breast cancer risk. The researchers assessed associations between overall breast cancer risk and ER+ versus ER− disease. They found 30 genes significantly associated with overall breast cancer risk, 20 genes associated with the ER+ subtype, and six genes with the ER− subtype. Read more here.

  • Using data from the Breast Cancer Association Consortium (BCAC), researchers evaluated associations between a new 313-variant polygenic risk score (PRS313) and individual risk factors among women of European ancestry. The analysis did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Read more here.

  • A polygenic risk score (PRS) is a number that estimates how an individual's genetic variants affect their risk of a specific disease. This 2020 study evaluated the relationship between a recently validated PRS of 313 germline variants (PRS313) and risk of contralateral breast cancer (CBC). In this study, higher PRS313 was associated with an increased risk of CBC. Read more here.

  • Previous research has shown high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. This project evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium. Study results suggested HOXB13 is not a material breast cancer susceptibility gene. Read more here.

  • Researchers assessed associations between mutations in panel-based genes and breast cancer risk in African-American women. In this 2020 study, mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer; RAD51D mutations were associated with high risk of ER-negative disease; moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer. Read more here.

  • A 2020 genome-wide association study identified 32 novel breast cancer susceptibility loci, 15 of which showed evidence for associations with at least one tumor feature. Read more here.

  • This 2020 study analyzed data from genome-wide association studies (GWAS) of European ancestry to estimate the number of common susceptibility variants (polygenicity) for 14 different cancers. The analysis demonstrated that polygenic risk scores (PRS) have potential for risk stratification for breast, colon, and prostate cancer. Read more here.

  • Researchers performed fine-scale mapping of the 2q35 breast cancer risk locus in European and Asian individuals using data from the Breast Cancer Association Consortium (BCAC). Fine-scale mapping is the process of mapping a gene to a chromosome, and then to the arm of that chromosome, and then to a specific band of the chromosome's arm. Previous studies have confirmed a breast cancer susceptibility locus on chromosome 2q35. This study confirmed three independent signals at 2q35 annotated by rs13387042 (signal 1), rs138522813 (signal 2), and rs16857609 (signal 3), and annotated variants at signals 2 and 3. Read more here.

  • Breast cancer susceptibility SNPs refer to variations in DNA building blocks that affect a person's risk of developing breast cancer. Researchers used a case-only GWAS design to compare SNP genotype frequencies between individuals with who had breast cancer and individuals with known BRCA1 or BRCA2 mutations who had breast cancer. The research team aimed to i) identify whether any SNPs affected breast cancer risk for women with BRCA1 or BRCA2 mutations but not for women without a BRCA mutation; and ii) evaluate 179 known breast cancer susceptibility SNPS to determine whether these SNPs interact with BRCA1 or BRCA2 mutations. Using this study design, researchers identified new associations with breast cancer for both BRCA1 and BRCA2 mutation carriers. Read more here.

  • Using data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS), researchers evaluated pathogenic variants (PVs) in nine breast cancer predisposition genes: BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. The research team also created polygenic risk scores (PRS), which evaluate how one person's risk compares to another person's based on their genetic composition, based on 105 common variants. Results from this study suggest that creating PRS may facilitate the personalization of breast cancer risk estimation among individuals with pathogeneic variants in predisposition genes. Read more here.

  • Researchers identified pathogenic variants in 28 cancer-predisposition genes using data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS) and assessed the association between these variants and risk of breast cancer. Within this study, pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer; pathogenic variants in PALB2 were associated with a moderate risk of breast cancer; pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer; and pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Read more here.

  • Gene-environment interactions (GxEs) are the ways in which the interaction between genes and the environment affect the expression of a genetic trait. This study examined interactions between eight environmental factors related to estrogen exposure and genes that are involved in estrogen metabolism. Using data from the Seoul Breast Cancer Study and the Breast Cancer Association Consortium, researchers identified interactions with NCOA1 and ESR1 that may affect breast cancer risk. Read more here.

  • Using specimens from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium, researchers conducted germline multigene cancer panel testing. Multigene cancer panel testing is a type of genetic testing that looks for mutations in multiple genes simultaneously. This study identified the prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes among women over age 65. Read more here.

  • Using data from the Breast Cancer Association Consortium (BCAC), researchers studied the levels of sex-hormones in study participant urine samples and then tested for an association between sex-hormone urine levels and breast cancer risk. Read more here.

  • Researchers applied Mendelian randomisation—a research method that uses genetic variation in genes whose functions are known to examine the relationship between modifiable risk factors and health outcomes—to data from the Breast Cancer Association Consortium (BCAC). This particular study examined the effect of cigarette smoking on breast cancer risk. Findings suggested that there may be a causal association between lifetime smoking exposure and breast cancer risk. The researchers did not find an association between cigarettes per day among smokers and breast cancer risk. Read more here.

  • For this study, researchers performed genome-wide association analyses within 15 subgroups of breast cancer patients using data from participants of European ancestry from the Breast Cancer Association Consortium (BCAC). Findings from this study suggested four loci—the physical location of a gene on a chromosome—that were associated with breast cancer-specific survival within three patient subgroups. Read more here.

  • Invasive lobular carcinoma (ILC) is a type of breast cancer that originates in the milk-producing glands of the breast. This study evaluated whether germline pathogenic variants (PVs)—gene changes that occur within a reproductive cell (either sperm or egg) and are then passed on to/inherited by the offspring—contribute to risk of ILC. The research team found that that PVs in the specific genes ATM, BRCA2, CDH1, CHEK2, and PALB2 were associated with an increased risk of ILC, whereas BRCA1 PVs were not. Read more here.

  • Previous research studies have established common breast cancer susceptibility variants—common genetic variants that may increase risk of breast cancer—that may function differently based on estrogen receptor status. Building on this existing knowledge, the research team used data from the Breast Cancer Association Consortium (BCAC) to evaluate these variants in relation to multiple tumor features, including ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade. Read more here.

  • Copy number variants (CNVs) are when the number of copies of a particular gene vary between different individual's genomes. This 2022 study evaluated the relationship between rare CNVs and risk of breast cancer among individuals of European ancestry. Read more here.

Endometrial Cancer

  • Estrogen has already been established to increase endometrial cancer risk, while progesterone combats estrogen’s effects. In 2010, researchers found genetic variation in the progesterone receptor gene (PGR) to be associated with an increased risk of endometrial cancer. Haplotypes (gene groups that passed down together) containing the PROGINS allele, which stunts PGR function, were associated with 34-77% increased risk of endometrial cancer among white women.  Read more here.

  • A susceptibility locus is an allele that influences risk but isn’t sufficient nor necessary to stop/cause expression of the disease. A 2012 study identified three new susceptibility loci at chromosomes 12p11, 12q24, and 21q21. Read more here.

  • A 2012 study investigated genetic variations in sex steroid metabolism and their effect on the relationship between hormone therapy and risk of endometrial cancer. Allele variations in CYP11A1, a gene involved in sex steroid metabolism, may alter the risk of estrogen therapy use on risk of postmenopausal endometrial cancer; however, further research is required.  Read more here.

  • A genome-wide association study targeting endometrial cancer found no new variants that reached genome-wide significance, but replicated previously identified associations near the locus HNF1B. The findings suggest that larger studies with specific tumor classification are necessary to find novel variants.  Read more here.

  • Researchers investigated whether SNPs previously associated with other cancers may be additionally associated with endometrial cancer. SNP rs7679673, found upstream of gene TET2 and previously reported to be associated with prostate cancer risk, was also associated with endometrial cancer risk but in the direction opposite to that for prostate cancer.  Read more here.

  • A 2016 genome-wide association study of women of European descent discovered one new susceptibility locus reaching genome-wide significance at chromosome 6p22.3, rs1740828, which is associated with greater risk of endometrial cancer.  Read more here.

  • A 2021 study used previously reported protein quantitative trait loci (pQTL) for 1434 plasma proteins to examine associations between genetically predicted circulating protein concentrations and risk of endometrial cancer. The research team found nine potential endometrial cancer-associated proteins. Read more here.

Non-Hodgkin Lymphoma

  • A 2009 study found CTS participants who had a family history of haematopoietic malignancy (tumors of the blood) were at an increased risk of non-Hodgkin’s lymphoma (NHL). Among this population, risk varied significantly by the gender of the affected family member. CTS participants who had female relative with lymphoma had a 2.5-fold greater risk of B-cell NHL than participants who did not have any family history of malignancy, while participants who reported having a male relative with lymphoma were not at increased risk.  Read more here.

Multiple Cancers

  • A 2016 genome-wide association study tested whether breast, ovarian and prostate cancers, which are all hormone-related cancers, had a shared genetic basis. This study found seven new cross-cancer loci: three loci associated with susceptibility to all three cancers, two loci associated with breast and ovarian cancer risk, and two loci associated with breast and prostate cancer risk.  Read more here.

  • A 2016 study using generated data from genome-wide association studies (GWAS) found that at least 24% the heritability for lung and bladder cancer may be attributable to genetic determinants of smoking.  Read more here.

  • A 2019 study found shared genetic components across multiple cancer types. Genetic correlations were shared between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. Several cancers were further found to be correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics.  Read more here.

  • Using existing genome-wide association studies (GWASs) summary statistics, this study evaluated the shared genetic basis of cancer risk across 14 different types of cancer. The research team found 13 pairs of cancers with local genetic correlations across eight distinct genomic regions, including the 5p15.33 region, which showed statistically significant local genetic correlations for multiple cancer pairs. Read more here.

Reproductive Health

  • A 2014 study found 123 signals at 106 loci associated with age at menarche. These genomic loci include genes that have also been implicated with body mass index and various diseases, including rare disorders of puberty. Loci DLK1-WDR25, MKRN3-MAGEL2, and KCNK9 exhibited parent-of-origin specific associations (for example, a trait that is only influenced by father’s chromosome). Findings suggest that these variants intersect to play a role in coordinating the time of puberty.  Read more here.

  • A 2015 study found that DNA damage response genes, including the first common variant of BRCA1, were associated with natural age at menopause. Later natural age at menopause increases breast cancer risk (approximately 6% increase in risk per year) but this is likely caused by prolonged sex hormone exposure, rather than DNA damage response gene mechanisms.  Read more here.

  • Researchers evaluated SNPs in growth factor genes associated with changes in mammographic density among non-Latina white CTS participants who had stopped estrogen-progestin combined therapy (EPT). The associations found were slight and potentially useful but not statistically significant.  Read more here.

bottom of page