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Cancer Research | Another Blog Carnival August 27, 2007

Posted by ramunas in media, research.
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Funky guys from BayBlab just started the first ever blog carnival on cancer research and have released the first issue.

There are broad topics covered as from synthetic biology, imaging, diet, smoking, clinical trials, pharmaceuticals and diagnostics field.

A very good start. This is going to be a substitution for Cancer Research today for me:)


GeneGenie#15 Hosted | BlogCarnival August 26, 2007

Posted by ramunas in cancer genetics, media.

I am proud to host #15 issue of GeneGenie – a blog carnival devoted to clinical genetics and initiated by ScienceRoll. This is gonna be my first blogcarnival ever.

I hope this issue will supposed to cover mostly cancer genetics topic, but feel free to submit any other genetic information by filling in the carnival submission form, leaving a link to your article in the comment field at the end of this post or just emailing me directly rjanavicius [at] gmail [dot] com.

GeneGenie#15 issue will be published on 9th September 2007.

Nomogram vs GeneSearch Genetic Test | Breast Cancer August 23, 2007

Posted by ramunas in bio-software, breast cancer, cancer genetics, GeneSearch.
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Several days ago an article from Memorial Sloan-Kettering Cancer Center, NY, USA, presented a user-friendly prediction model (nomogram) based on a large data set to assist in predicting the presence of sentinel lymph node (SLN) metastasis for a specific patient, which is important prognostic factor.

After multivariate analysis with SLN metastasis were associated several factors: age, tumor size, tumor type, lymphovascular invasion, tumor location, multifocality, and estrogen and progesterone receptors [ref.]. The nomogram was accurate, discriminating and properly validated (a model was subsequently applied to 1,545 sequential SLN biopsies.)

Because newly diagnosed breast cancer patients are increasingly interested in information about their disease, this validated nomogram for risk estimation could be useful tool for physicians and patients to accurately predict the likelihood of SLN metastasis.

A nice computerized version (Macromedia Flash 6.0) of the nomogram is available on their website.

This tool, known as a nomogram, can be used to calculate the likelihood that breast cancer that has spread to the sentinel lymph nodes has also spread to additional lymph nodes under the arm (axilla). It is designed to individualize the risk estimate for each patient — a key factor in deciding whether additional surgery is likely to be beneficial, website states.

Obviously, it is not a substitute for medical advise, diagnosis or treatment but seems to be quite useful addition for risk estimation.

Researchers recommends that this tool should be used by physicians only. Patients should use this tool only in consultation with their physicians.

Also, I think it would be of great interest to compare this Breast Cancer Nomogram results with recently FDA approved Johnson&Johnsons GeneSearch™ Breast Lymph Node (BLN) assays results, which claims to detect the spread of breast cancer into the lymph nodes by analyzing the level of metastatic tumor expression markers.

Genetic Test Disclosure | BRCA Study August 17, 2007

Posted by ramunas in BRCA, breast cancer, cancer genetics, genetic testing, hereditary cancer.

Generally, principles of predictive testing for cancer predisposition are the same as for the adult-onset diseases. Therefore it is not allowed to test children till the age of 18 in most countries because of the lack of effective preventative interventions at a young age. Such an early knowledge could result in unnecessary anxiety and worries. Notable exceptions are MEN 2 (A and B) syndrome, Von-Hippel-Lindau syndrome and familial adenomatous polyposis (FAP), also other rare early tumor predisposition syndromes, when there is high risk of cancer in an early ages and preventative measures are effective even at early childhood (e.g. for MEN2A thyroidectomy is advised till the age of 5 years and as young as 2 years for MEN2B, because metastases has been reported. (source))

However, a new study in the forthcoming Aug. 20 Journal of Clinical Oncology about parental communication of BRCA results to children under the age of 25 years old, reveals that more than half of the parents told their children about their genetic test results.

“Some parents reported that their children didn’t seem to understand the significance of the information shared, and that some had initial negative reactions. Further research is needed to understand the impact of this communication on these children in order to provide optimal counseling for families with a genetic risk of cancer” said the study’s author, Angela Bradbury, M.D., director of Fox Chase Cancer Center’s Family Risk Assessment Program.

This study probably rely on published data from previous presentations.

More about patients attitudes towards positive BRCA genetic test result read in EyeOnDNA recent post, where around half women in a BRCA+ group had taken no preventive action.

Variants of Hormonal Axis Tagged | Breast Cancer August 16, 2007

Posted by ramunas in breast cancer, cancer genetics, genetic testing, research.
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A study from Rotterdam, Erasmus Medical Center, the Netherlands, just published in OpenAccess journal “Breast Cancer Research“, retrospectively investigates the prognostic significance of two variants of genes involved in the in hypothalamic-pituitary-gonadal (HPG) axis, i.e. the Gonadotropin-Releasing Hormone (GnRH) 16Trp/Ser genotype and Luteinizing Hormone receptor (LHR) insLQ variant (common polymorphic CTCCAG insertion), in collected premenopausal breast cancer patients with a long follow-up (medium – 11 years).

Polymorphic variation in genes regulating estrogen production may partly explain differences in susceptibility, clinical presentation and outcome of breast cancer between individuals or population, article says.

Researchers found, that patients carrying both the GnRH 16Ser and LHR insLQ allele (approximately 25% from a total of 278 cases) showed a significant increased (doubling) risk of relapse, which was independent of traditional prognostic factors (hazard ratio (HR) =2.14; 95% CI 1.32-3.45; P= 0.002). Neither LHR insLQ nor GnRH 16Ser genotypes influence the risk of breast cancer development (ref.)

I think, it is interesting finding, and when confirmed in a further larger, prospective studies, genetic testing for these polymorphisms may provide additional prognostic information for premenopausal breast cancer patients in clinical practice and may result in tailored endocrine treatment of these patients.

(image source)

Novel Immune Biomarker | Prostate Cancer August 16, 2007

Posted by ramunas in cancer genetics, prostate cancer, research.
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Being also involved in cancer immunology, this article from Mayo Clinic published in Cancer Research last week, is of great interest for me – researchers for the first time have identified immune molecule B7-H3 as a biomarker, that appears to play a role in prostate cancer development and in predicting cancer recurrence and progression after surgery.

This study demonstrate that nearly all normal, pre-malignant and cancerous prostate cells have B7-H3 on their surface. Unlike PSA, B7-H3 stays attached to the surface of prostate cancer cells and does not appear to migrate, thus making B7-H3 a particularly attractive target for therapy. The researchers believe that B7-H3 kills or paralyzes immune cells that are trying to attack the cancer. Their findings indicate that B7-H3 may prove useful as a diagnostic, prognostic and even therapeutic tool because it is stably or increasingly displayed by tumor cells as prostate cancers develop — even after initiation of anti-hormone therapy, which is the most common treatment for advanced prostate cancer, says EurekaAlerts.

The physician-research team examined tissue from 338 consecutive patients who had cancers confined to the prostate and were treated exclusively with a radical prostatectomy (surgery to remove the prostate) between 1995 and 1998. All tumors and precancerous tissues displayed B7-H3, but patients with the highest levels of B7-H3 within their prostate tumors (19.8 percent) were four times more likely to experience cancer progression compared to those with weak levels of B7-H3 within their tumors. Moderate levels of B7-H3 also correlated with a slightly higher risk of recurrence (35 percent) (via).

B7-H3, a member of the B7 family of the Ig superfamily proteins, is expressed on the surface of the antigen-presenting cells and down-regulates T cell functions by engaging an unknown counterreceptor on T cells [ref.]. Mayo Clinic Cancer Center was the first to discover the B7-H family of immune molecules in 2001. They showed that B7-H3 and other members of the B7-H family, such as B7-H1, can have an inhibitory function and actually protect cancers as they develop [via].

To understand how B7-H3 affects the immune system, and whether a mutation of B7-H3 is involved in the anti-immune activity, more research is necessary. Mayo is planning clinical trials for a number of cancers in late 2008, and researchers are currently developing the necessary therapeutic antibodies to be used in these studies. Investigators expect that clinical laboratory tests for the B7-H proteins may become available at Mayo to assist with the assessment of patients with kidney cancer by late 2007 or early 2008, and then for prostate cancer patients shortly thereafter [ref.] .

Well, B7-H3 molecule is already patented (what a shame!) not only by Mayo, who already holds patents to B7-H1, B7-B4 (check it here) and has licensed the patent rights to Medarex, Inc., but also by pharmaceutical company Wyeth for use as immunoregulatory agent (here it is). In addition, Mayo Clinic has filed a patent application related to B7-H3. Drs. E. Kwon, T. Roth and Y. Sheinin and Mses. C. Lohse and S. Kuntz are inventors of this technology. Track it further on PatentLens or Google Patent Search.

(photo source: B7-H3 immunohistochemistry)

MRI Is Better for Early Breast Cancer Detection | Lancet study August 14, 2007

Posted by ramunas in breast cancer, cancer genetics, research, technology.
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Last week issue of medical journal the Lancet presents an important data from 5-years perspective study, which shows that MRI (magnetic resonance imaging) outperforms conventional mammography for detection of ductal carcinoma in situ (DCIS), an early pre-invasive breast cancer which arises in the milk ducts (listen to the audio podcast stream from Lancet).

“MRI is more powerful and accurate for diagnosing pre-invasive breast cancer called ductal carcinoma in situ (DCIS),” concluded lead research Dr. Christiane Kuhl, from the Department of Radiology at the University of Bonn, Germany [via].

In the study, Kuhl and colleagues collected data on more than 7,300 women over five years. In addition to mammograms, the women were also given MRIs. The researchers wanted to see if MRIs could detect DCIS. The study found that x-ray based mammograms detect only 56% of early lesions in high risk women compared with 92% when magnetic resonance imaging scans (MRI) are used.

Moreover, of the 89 women diagnosed with “high grade” DCIS — the ones most likely to develop into cancer — 98 percent were found by MRI, compared with 52 percent found by mammography. In addition, 48 percent were missed by mammography but found by MRI alone (via).

Age, menopausal status, personal or family history of breast cancer or of benign breast disease, and breast density of women with MRI-only diagnosed DCIS did not differ significantly from those of women with mammography-diagnosed DCIS, study abstract states.

Cancer screening programmes are failing to detect nearly half of the earliest cases of breast cancer according to research which suggests women’s lives could be saved if all were offered hi-tech MRI scans, the Guardian states.

“If you picked up all cases of ductal carcinoma in situ [DCIS] you would prevent virtually all cases of breast cancer. Our finding that MRI is superior to mammography in detecting it turns things upside down.”, researchers said.

High-grade DCIS almost always becomes invasive and does so after a short time, Kuhl explained. “When it becomes invasive, it is biologically aggressive — that means it kills,” she said.

In contrast, low-grade DCIS usually remains within the duct and poses no threat. In fact, women can have low-grade DCIS for a lifetime with no ill effects, Kuhl said.

Also, MRI was not associated with many false positive findings. The positive predictive value of both methods was similar — 55 percent for mammography and 59 percent for MRI, the researchers reported.

“These findings can only lead to the conclusion that MRI outperforms mammography in tumour detection and diagnosis. MRI should thus no longer be regarded as an adjunct to mammography but as a distinct method to detect breast cancer in its earliest stage.”, said experts from the Radboud University Nijmegen Medical Centre in the Netherlands.

However, despite the technology’s advantages, its cost and a lack of people skilled at reading breast MRIs means it won’t replace mammograms any time soon, experts say.

“Also, MRI is more difficult to read, and you have to use different criteria to diagnose DCIS than for invasive breast cancer.” Since MRI is used less often than mammography “the number of radiologists who are experienced in interpreting breast MRIs is far smaller than the number of radiologists who are able to accurately interpret a mammogram”.

This is the beginning of the death of mammography, but that is going to be a long death,” Kuhl predicted. (via).

The study raises new questions about the national breast cancer screening programmes, which sees all women between the ages of 50 and 70 called in for regular mammograms but not MRI scans (at two-yearly visits in my country.) Only younger women at high risk of breast cancer are offered the more expensive MRI scans, because mammography is not informative in premenopausal women due to dense breast tissue.

Anyway, the results should be interpreted with caution (ref.):

“This study says that potentially mammograms are missing half of women with DCIS. The implication is that mammograms may not be the most sensitive way of finding early breast cancer, but it is clearly saying that more research is needed. A lot of women walk around with it without it being invasive or harmful. Some clinicians argue that we are over-diagnosing and over-treating already. It doesn’t seem practical to do MRI on every woman. It’s costly and very time-consuming as well”, says consultant nurse at Breast Cancer Care.

“The programme uses mammography to screen all women in the UK aged 50 or more for breast cancer. The results in the Lancet are not representative of the screening population, and so have to be interpreted with care”, states Julietta Patnick, director of UK NHS cancer screening programmes.

Senior policy officer at Breakthrough Breast Cancer, said: “This is an interesting but complex study which gives us more information about the detection of early breast changes. However, it is important to note that the women who took part in this study had a higher chance of an abnormality being found and therefore are not representative of the general population.”

What is a connection between MRI, DCIS and cancer genetics, you may wonder? It is now well established, that BRCA1-positive breast tissue has different histopathological appearance and course – its usually G3, estrogen negative and expressing basal-like phenotype. Recently published studies from Canada, Italy, Germany (btw, by the same author), the Netherlands and UK (MARIBS study) all similarly showed, that MRI outperforms mammography in BRCA1 breast cancers and annual MRI is now included as addition to mammography for TP53, BRCA1 and BRCA2 mutation carriers screening programs, performed from 30 till 49 years in UK and other countries. Cost effectiveness of MRI is also proven.

MRI procedure is more invasive than mammography, because contrast enhancing substance must be injected intravenously and special equipment is used:

The genetics of DCIS is also interesting topic – it is only several years since it was shown, that DCIS cases actually have the same proportion of BRCA1 and BCRA2 mutation as invasive breast cancer has – mutations were found in a significant proportion of women with DCIS who presented for hereditary risk assessment [via]. DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are non-carriers, but occurs at an earlier age [via].

Hereditary Cancer Public Perception | Cancerbackup August 13, 2007

Posted by ramunas in cancer genetics, familial cancer, hereditary cancer, media, sporadic cancer.

There were recently data released from survey performed by information charity Cancerbackup and Genes Reunited during collaborative What Now? campaign, which is aimed to highlight the myths that exist around cancer and genetics.

This survey reveals the unnecessary worry that exists because people overestimate their cancer risk based on their family history.

Of over 1,000 people that responded to the survey 60% incorrectly thought that family history was the biggest risk factor for cancer and only 15 per cent knew that it is actually age – two thirds of cancer incidence is in people over 65-years-old, says MedicalNewsToday.

I generally look quite carefully to such public surveys and media trends for interpreting results out of context – it is easy to dismiss important findings then.

It is now well established that genetic factors play an important role in causing cancer, therefore arguing that most cancer is non – genetic can be confusive both for public and other health care providers. “All cancer is genetic but some cancers are more genetic than others”. That actually means , that in most cases the causal mutations are not inherited but are acquired somatically, possibly as part of the normal aging process or as a result of prolonged exposure to particular carcinogens. Saying “genetics” does not necessarily means “something inherited”.

The cancer risk perception is a complex and personal feeling, and depends on a family history. Therefore from these (only) 1000 responders there could be a proportion of people with a strong family history, which naturally experiencing higher family history attribution. I remember one of my patient, who came and said – I definitely have a mutation – and she was right, because her mother, maternal aunt and grandmother died of breast cancer in an early age and she was also affected. For families like this cancer family history is really number one risk factor.

Cancer is so common that probably everyone of us has (or had) some relative with this disease. Some common cancers in the family may have occured by chance, but again, age is an important factor, which could indicate that cancer is occurring due genetic predisposition: young age is considered to be <50 years for breast, stomach, pancreas, bowel and prostate. For ovarian cancer, occurrence in an older age is still likely to be significant factor, if there are other family members affected with either ovarian or early breast cancer. Therefore, evaluating family history, the important features suggestive of an inherited susceptibility to cancer are (ref.):

  • early age of onset
  • bilaterality of disease (i.e. multiple primary tumors)
  • multiple cases on one side of the family (two or more first/second-degree relatives):

The vast majority of people realized that it is not just breast cancer that can occur because of an inherited genetic link. However, they didn’t realize that in order to suspect such a link, generally the same type of cancer (or cancers that are known to run together such as breast and ovarian or bowel and womb cancers) would need to occur in family members on the same side of the family (via).

  • other related early-onset tumors (“patterns” of associated cancers, e.g. breast and ovarian, colon and endometrial)
  • rare cancers (e.g. two or more relatives with the osteosarcoma).
  • ethic origin (Ashkenazi, Icelandic, Eastern European, Dutch etc).

Ageing is definitely an important risk factor, and cancer risk increases with age, with the highest incidence occurring over age 65 (64% (64 in 100) of all newly diagnosed cancers occur in people aged 65 years or more [via]). This may be due to less affective immune responses in the elderly or a lifetime of exposures. Probably, a cancer is a natural evolutionary fate of a cell in multicellular organism.

It is important to remember some sobering cancer risk factors (source: Offit, 1998):

  • diet – 35% (mainly alcohol, high protein intake, smoked/curred food, high fat intake)
  • tobacco use – 30% (mouth, pharynx, larynx, esophagus, stomach, lung, kidney, pancreas, bladder, cervix (sic!)).
  • hereditary factors – 5-10%
  • occupational exposures – 5%
  • radiation – 1-2%
  • viruses – 1-2%
  • miscellaneous – 16-23%

Bolded factors (65%) are important modifiable lifestyle factors for general population and tobacco is a single most important avoidable cancer-causing agent. However, the extent to which lifestyle changes can modify the cancer risk in individuals with inherited predispositions to cancer is unclear.

When asked what percentage of cancers occur because of a known inherited genetic link, only 13 per cent of people knew that just 5-10 per cent of all cancers are known to be hereditary. Furthermore, a quarter of people thought that between 50 – 100 per cent of cancers are hereditary (via).

Yes, that is true. But again – there is another type of cancer – familial, which could account up to 30% of cases. For example, up to 27% of breast cancer can be attributed to heritable factors from twin studies. Familial type refers to multifactorial inheritance, implying the interaction of additive polygenes with the environment, and probably plays a role in around 20-25% of cases.

It is important to remember general population risks (Western societies)

  • lifetime risk for any cancer -(1/3 – for women, 1/2 – for men
  • breast cancer (female) – 1/10 – 1/12
  • prostate cancer (asymptomatic) – 1/3
  • prostate cancer (clinicaly diagnosed) – 1/10
  • colon cancer – 1/25 – 1/50
  • ovarian cancer – 1/70
  • proportion of common cancers which is inherited – <1/10.

A staggering 91 per cent of people surveyed in a Cancerbackup poll on Genes Reunited’s website, thought that if one of their relatives had cancer, they are at a greater risk than average of getting it themselves. In actual fact in the majority of cases this would not significantly increase someone’s risk at all.

Again, I would interpret this with caution. Family history is an important risk factor for breast or ovarian cancer.

Although reproductive, demographic, and lifestyle factors affect risk of ovarian cancer, the single greatest ovarian cancer risk factor is a family history of the disease. A large meta-analysis of 15 published studies estimated an odds ratio (OR) of 3.1 for the risk of ovarian cancer associated with at least one first-degree relative with ovarian cancer, cancer.gov claims.

So, a family history of ovarian cancer increases the risk by threefold, which, I think is not so unsignificant factor.

Also, in a pooled analysis of 38 studies, the relative risk of breast cancer conferred by a first-degree relative with breast cancer was 2.1 (95% confidence interval [CI], 2.0-2.2). Risk increases with the number of affected relatives and age at diagnosis.

Textbooks (this and this) states, that the presence of a first-degree relative with breast cancer increases the risk 1,5-4.0-fold, depending on the age of the affected family member.

Having one affected first-degree relative increases the risk of colon cancer by three- to fourfold and having several relatives with colorectal cancer may be consistent with a hereditary cancer syndrome, Katherine Schneider writes.

Obviously, one or two cases of cancer in a family does not necessarily mean that there is a hereditary cancer syndrome in that family, but familial cases are also important to distinguish.

In conclusion, patient concern for cancer is common and valid reason for referral to genetic counseling. About 60% of women are referred to a familial breast cancer clinics due to their own initiatives. It was already shown, that from clinical attendees with a family history of breast cancer in UK, only 25% belonged to high risk, 25% had population level or lower risk, and 50% reached sufficient risk level for screening. “A women who has a low risk of being cancer-prone, but who is worried by her family history, should have access to consultation”, Eisinger et al. states. Often risk assessment alleviates fear and anxiety. Genetic counseling and testing generally results in lower psychological distress, both for those individuals who test negative and those who test positive.

Dr. James Mackay, Clinical oncologist and medical director of Opaldia, a private UK genetic testing company, and scientific advisor for a private polish genetic testing company Read-Gene, highlights some important questions of cancer genetics, which I’ve found in Cancerbackup YouTube account:

Anyway, I’ve missed more opinions of other independent clinical cancer geneticists, especially from academical setting.

Association With Prostate and Colon Cancer | 8q24 August 7, 2007

Posted by ramunas in cancer genetics, colon cancer, familial cancer, genetic testing, prostate cancer.

Recent two years were (and continues to be) very prolific in the research of common genetic variants, implicated in cancer, notably breast, prostate and colon. In this post I’ll summarize advances surrounding 8q24 region and its importance in prostate and colon cancer. All data of conducted association studies were published in high impact factor journals and repeatedly confirmed by independent researchers in different populations what means there is really something in the region 8q24.

In 2006 two variants of chromosome 8q24 were reported to be associated with increased risk of prostate cancer (PrCA):

  • Dr. Kari Stefansson group (from infamous deCODE Genetics, Iceland) reported region 8q24, identified through a genome-wide linkage scan study of Icelandic prostate cancer (PrCA) families [1]. Common variant allele -8 (microsatellite DG8S737 ) was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US – odds ratio (OR) 1.79 for Icelandic patients. The frequencies of the DG8S737 -8 allele and the rs1447295 A allele were significantly greater in the men with prostate cancer. In the Icelandic samples, allele -8 of DG8S737 and allele A of rs1447295 were substantially correlated. The combined results for the European groups yielded an estimated OR of 1.62 for DG8S737 -8 and an OR of 1.51 for rs1447295 A. Genotyping of African American men with prostate cancer with controls resulted in the odds ratio 1.60. The estimated population attributable risk for the – 8 allele (DG8S737) was 16% among African-Americans versus 5% to 11% among men of European ancestry. The “relatively high” population frequency of the – 8 allele in African Americans, “which confers an estimated population attributable risk of about 16% and could alone produce more than a 10% greater incidence of prostate cancer in African Americans than in European Americans,” the authors suggest [via].

In all four case-control groups, the frequency of cancers with DG8S737 -8 was significantly greater in men with PrCA with higher Gleason scores than among those with lower scores and might have a stronger association with the more aggressive forms.There is no immediate clinical impact of the finding, researchers said, because it applies to the population at large rather than individuals.

  • On March 2007 Australian population-based case-control study concluded that the A allele of rs1447295 is associated with a higher risk of PrCA regardless of tumor aggressiveness, suggesting that such a variant, or a variant in linkage disequilibrium with it, plays a role early in prostate carcinogenesis [2].
  • On April 2007 a study from US further confirms the importance of these two polymorphic variants (rs1447295 and DG8S737) as risk factors for PrCA [3].

A recent three new reports [4-6] have independently found multiple neighboring regions (rs1447295, rs16901979 and rs6983267) within a 600-kb segment of chromosome 8q24 that harbor variants associated with disease which are summarized in this scheme from review by John Witte in Nature Genetics:

The rs1447295 location could be responsible for about 7 % of PrCA cases in white men of north European descent. Thus, taken together with rs6983267, these two genetic changes could account for as much as one quarter of prostate cancer cases in white men. The increased risk conferred by these loci was observed for all age groups studied [via].

Around seven SNP’s in 8q24 play a significant role in prostate cancer [via, also Ref. 4, 6].

So, it was known that variants on chromosome 8q24 contribute risk for prostate cancer, but Haiman CA et al. decided to test whether they also modulate risk for colorectal cancer (ColCA). Interestingly, SNP rs6983267 was also significantly associated with ColCA (odds ratio = 1.22; P = 4.4 x 10(-6)).

In July 8 online edition of Nature Genetics there are even three independent replication studies published for rs6983267 and ColCA from US, UK and Canada [7-9].

The number of people who carry the variant on region 8q24 includes about half of the populations studied, researchers say. “In other words, it is very common in the general population,” said Dr. Malcolm Dunlop, of Cancer Research UK and the University of Edinburgh, Scotland. [via]

Overall, carriers of this variant have about a 20 percent higher risk of developing a colorectal malignancy compared to non-carriers, Dunlop team reports. Between 4 to 9 percent of all bowel cancers” may be traced to this particular (8q24) chromosomal locus [via].

Similar results were found in a U.S. study that was led by Christopher Haiman of the University of Southern California, Los Angeles: the rs6983267 variant conferred about a 22 percent increase in colorectal cancer risk [via].

“This is the first common genetic risk factor that has been reproducibly associated with risks in multiple cancers,” Haiman told reporters. “The association observed with this variant in both prostate and colorectal cancer provides very strong support for the hypothesis that there may be a common biological mechanism underlying cancer risk in this region of the genome.”

However, rs6983267 was found more frequently in some ethnicities than in others. “The frequency of this specific genetic variation varies widely in the population — from about 85 percent of African-Americans to as low as 30 percent of Japanese,” Haiman said.

“Although individually these markers may only contribute small amounts of risk, collectively, in certain individuals, they may actually have composite risks which are comparable to that of known, high-risk [mutations],” explained Dr. Richard Houlston, of the Institute of Cancer Research in Sutton, U.K. [via]

A consortium from Israel, Spain and the United States – uncovered a similar connection between genetic variations on 8q24 and a rise in colon cancer risk [10].

Chromosome 8q24 harbors oncogenes known to be involved in pathogenesis of colorectal cancer as well as uncharacterized genetic variants that have recently been shown to influence inherited risk of prostate cancer.

“These are encouraging findings, but obviously we need a lot more information about the genetic implications,” said Dr. Durado Brooks, the society’s director of prostate and colorectal cancer. “Genetic tests that might assess people’s risk or help in cancer diagnosis are still years away, and, for now, the new finding will not in any way significantly alter clinical practice. Ideally tests might someday be developed to spot genes like rs6983267, such that you could tailor interventions such as more intensive [patient] surveillance and even prevention. This is big step forward, but there is more to come.”he said. [via]


  1. Laufey Amundadottir et al. A common variant associated with prostate cancer in European and African populations, Nat Genet 38 (6), 652-8 (Jun 2006)
  2. Gianluca Severi et al. The common variant rs1447295 on chromosome 8q24 and prostate cancer risk: results from an Australian population-based case-control study, Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):610-2
  3. Liang Wang et al. Two Common Chromosome 8q24 Variants Are Associated with Increased Risk for Prostate Cancer Cancer Research 67 (7), 2944-50 (01 Apr 2007)
  4. Gudmundsson J et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet. 2007 May;39(5):631-7. Epub 2007 Apr 1.
  5. Haiman CA et al. Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet. 2007 May;39(5):638-44. Epub 2007 Apr 1.
  6. Yeager M et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May;39(5):645-9. Epub 2007 Apr 1.
  7. Haiman CA et al. A common genetic risk factor for colorectal and prostate cancer. Nat Genet. 2007 Aug;39(8):954-6. Epub 2007 Jul 8.
  8. Tomlinson I et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007 Aug;39(8):984-988. Epub 2007 Jul 8.
  9. Zanke BW et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet. 2007 Aug;39(8):989-994. Epub 2007 Jul 8.
  10. Gruber SB et al. Genetic Variation in 8q24 Associated with Risk of Colorectal Cancer. Cancer Biol Ther. 2007 Jul 2;6(7) [Epub ahead of print]

Characteristics of Hereditary, Familial and Sporadic Cancer Syndromes August 1, 2007

Posted by ramunas in basic concepts, cancer genetics, familial cancer, hereditary cancer, sporadic cancer.

In a recently published recommendations for risk assessment and genetic counseling for hereditary breast and ovarian cancer (HBOC) in a Journal of Genetic Counseling, there is a very useful definition of 3 main type of cancer (from a geneticist point of view):
I. “Hereditary Cancer type” characteristics:

  • Apparently autosomal dominant transmission of specific cancer type(s)
  • Earlier age of onset of cancers than is typical
  • Multiple primary cancers in an individual
  • Clustering of rare cancers
  • Bilateral or multifocal cancers
  • First degree relatives of mutation carriers are at 50% risk to have the same mutation
  • Incomplete penetrance and variable expressivity, such that obligate carriers of the family mutation may be cancer-free and the age of diagnosis of cancer among relatives will vary
  • Those who do not have the familial mutation have the general population risk for cancer

II. “Familial Cancer type” chatacteristics:

  • More cases of a specific type(s) of cancer within a family than statistically expected, but no specific pattern of inheritance
  • Age of onset variable
  • May result from chance clustering of sporadic cases
  • May result from common genetic background, similar environment and/or lifestyle factors
  • Does not usually exhibit classical features of hereditary cancer syndromes

III. “Sporadic Cancers type” characteristics:

  • Cancers in the family are likely due to nonhereditary causes
  • Typical age of onset
  • Even if there is more than one case in the family, there is no particular pattern of inheritance
  • Very low likelihood that genetic susceptibility testing will reveal a mutation; testing with available technology/knowledge level will likely not provide additional information about cancer risk.

This classification can help in quantifying risks to individual family members and developing a plan for cancer screening, prevention, risk reduction and psychosocial support and counseling. It also helps in the determination of whether genetic testing is appropriate for the family, and if so, which relative(s) would be the appropriate individual(s) to test. Unfortunately, the separation of families into hereditary, familial, and sporadic cancer is often not precise.

With a growing knowledge in low penetrance genes those families which were regarded as sporadic could be reclassified to familial cases. For more information please also take a look at my first post on this blog.