Review of Health Studies Relevant to Lawrence Livermore National Laboratory and the Surrounding Community
LAWRENCE LIVERMORE NATIONAL LABORATORY, MAIN SITE (USDOE)
LIVERMORE, ALAMEDA COUNTY, CALIFORNIA
|Report Date and Reference||Study Authors/Sponsor||Main Findings||Dates Studied or Study reviewed|
|1980 (37,38)||Resource for Cancer Epidemiology (RCE) of California Department of Health Services (CDHS) (now Cancer Surveillance Section, California Cancer Registry) (Report #1)||The incidence of melanoma among LLNL employees is about 3 times higher than in the community.||1972-1977|
|1980 (54)||Joint Legislative Audit Committee, California Legislature||Panel of expert scientists convened by the California Legislature concludes the study (Report #1) was correctly conducted; no links could be drawn to LLNL, but the findings were significant enough to require further investigation.||Review of Report #1|
|1980 (55)||Ad hoc advisory board/US Department of Energy (DOE)||Board convened by DOE agrees with Report #1 that melanoma among LLNL employees is 3 to 4 times higher than general population; states cause of excess not yet found.||Review of Report #1|
|1985 (39)||RCE (Report #2)||Cancer rates in general are not elevated among LLNL employees; |
Melanoma is 3 times higher than expected.
|1986 (40)||Kaiser Permanente Medical Care Program (pre-paid health plan) (KPMCP)||Melanoma rates in LLNL employees are about 3 times higher than KPMCP members overall.||1976-1980|
|1984 (49,50)||RCE (Report #3)||Several occupational factors are strongly associated with melanoma: ||1969-1980|
|1985 (56)||LLNL||This document was commissioned by LLNL to synthesize the comments of seven experts that LLNL had commissioned to review RCE Reports 1, 2 and 3. The authors generally felt the following to be unresolved: whether there was a real excess of melanoma among LLNL employees, and whether the excess was causally related to factors in the LLNL environment.||Review of Reports # 1, 2, & 3|
|1987 (57)||University of North Carolina (UNC) (independent review of Report #3 requested by LLNL)||Researchers at UNC review Report #3 and conclude it was well conducted, although they consider the causal nature of the factors to be overstated in the RCE report. Three factors identified by RCE remain significant: |
The study also analyzes radiation badge data not available to RCE and find no association between exposure to ionizing radiation (on the basis of badges) and melanoma.
|Review of Report #3|
|1987 (41)||LLNL in collaboration with the University of California, San Francisco (UCSF)||The rate of melanoma increases across three time periods, and melanoma thickness decreases during these periods: "pre-awareness, early awareness, and aggressive surveillance."||1969-1975 |
|1990 (42)||LLNL in collaboration with UCSF||LLNL lesions are thinner than community lesions. In the early study years, there is little difference, but then both decline, although the LLNL decline is greater. The authors suggest that earlier diagnosis among LLNL employees would result in thinner lesions, and that this might have contributed to the excess in the years following increased awareness.||1976-1984|
|1992 (43)||LLNL in collaboration with Stanford and Northern California Cancer Registry||The authors find melanoma rates to be 2.9 times higher than expected for men at LLNL and 2.4 times higher for women. They find that LLNL employees had thinner lesions than community members, suggesting that increased surveillance could have contributed to the excess melanoma. However, in our analysis, statistical testing of their numbers finds the difference too small/random to be distinguishable from chance.||1974-1985|
|1993 (45)||KPMCP (independent study)||LLNL tumors were thinner than the comparison group until 1976, after which there was no difference, as the tumor thickness among the non-LLNL employees decreased in the second time period of the study, suggesting that surveillance bias could be a reason for elevated rates in the earlier time period but not in the later period.||1970-1984 |
(1970-1976 versus 1977-1984)
|1994 (58)||University of North Carolina (UNC) (independent review)||In an extension of the previous UNC review of Report #3, the independent experts investigate the inconsistency between reported radiation exposure and individual dosimetry readings, using dosimetry readings to create an exposure index. They find the radiation exposure index to be highly associated with melanoma case status (Odds Ratio=10.8), and that the reported odds ratios for employment in proximity to radiation withstood intensive scrutiny, suggesting Report #3 results may be valid.||Review of Report #3|
|1994 (3,51)||LLNL||LLNL does not find occupational factors (exposure to ionizing radiation and chemicals) related to melanoma risk among employees.||1969-1989|
|1995 (60)||RCE||Overall rates of cancer in children and young adults in Livermore are not elevated. Among children and young adults residing in Livermore, melanoma rates are 2.4 times higher than expected, and among persons age 0-24 who had been born in Livermore, the rate is 6.4 times higher than expected.||1960-1991|
|1996 (61)||California Cancer Registry (formerly RCE)||Cancer incidence among Livermore residents is similar to the Bay Area as a whole. In the tract near LLNL, the number of melanomas is above expected, but within a range that could have occurred by chance.||1988-1993|
|1996 (62)||California Birth Defects Monitoring Program, CDHS.||The overall rate of birth defects in Livermore is very similar to statewide rates.||1983-1989|
|2001 (46,47)||LLNL requested review||The unpublished cancer data review finds overall fewer cases of cancer among LLNL employees than expected, except that men had a 38% higher rate of melanoma, although the frequency of melanoma has declined in the past 15 years.||1974-1997|
|Years of study||1969-1980 males||1969-1980 females||1972-1977 white males||1976-1980 males and females||1974-1985 males||1974-1985 females||1974-1997 males||1985-1997 males|
|Melanoma rate in LLNL vs. comparison group||3.25||5.19||3||3.2||2.9||2.4||1.38||Rates have returned to "Bay-area average" (47)|
|Data/Study source||RCE 1985 (39)||RCE 1985 (39)||RCE 1981 (37)||KPMCP 1986 (40)||LLNL & Stanford 1992 (43)||LLNL & Stanford 1992 (43)||LLNL-requested review of cancer data, 2001, pending publication (46,47)||LLNL-requested review of cancer data, 2001, pending publication (46,47)|
Note: all elevations are statistically significant, p <0.05.
|Years of study and population studied||Children and young adults, Livermore residents; 1960-1991 |
(Standardized Incidence Ratio, 95% CI)
|Children and young adults, born in Livermore, 1960-1991 |
(Standardized Incidence Ratio, 95% CI)
|LLNL dependents, KPMCP members, 20-64 years of age, 1976-1980 |
(Relative risk, 95% CI)
|8 Livermore census tracts; 1988-1993, |
|Livermore census tract located next to LLNL; 1988-1993, |
|Total cancers||1.2 (1.0-1.4)||1.1 (0.8-1.5)||--||1.06 (0.87 - 1.01)||0.90 (0.76 - 1.06)|
|Leukemias||1.2 (0.7-1.7)||1.0 (0.4-1.8)||--||1.04 (0.57 - 1.73)||0.80 (0.12 - 2.52)|
|Non-Hodgkin's lymphoma||0.7 (0.2-1.7)||0.8 (0.1-2.8)||--||--||--|
|Hodgkin's disease||0.7 (0.3-1.5)||0.7 (0.1-2.7)||--||--||--|
|Brain*||1.3 (0.8-2.1)||0.9 (0.3-2.2)||--||1.17 (0.67 - 1.89)||1.40 (0.40 - 3.44)|
(0.9 - 4.7)
(0.76 - 1.54)
(0.81 - 2.91)
|Data/Study source||CDHS 1995 (60)||CDHS 1995 (60)||KPMCP 1986 (40)||CDHS 1996 (61)||CDHS 1996 (61)|
*Brain cancer for 1960-1969: SIR=3.0 (95% CI=1.4-5.8).
|Page of comment/ Section of report||Comment||CDHS Response|
|Page 1, Paragraph 3||"The CDHS reviewers chose to ignore the most recently available cancer incidence report (updated through 1997), which could have been obtained from LLNL, and instead, cited two newspaper articles written by a reporter regarding the study findings." |
" Nor did CHDS contact the medical department at LLNL to obtain the report (personal communiqué with J. Seward, Director)."
|Page 1, Paragraph 3||"Had CHDS reviewed the report, they would have noted that the apparent excess appears to vanish by 1986 (Whorton 2003)."||This health consultation has always contained a review of this study, including stating: "According to a recent cancer review requested by LLNL, melanoma rates have apparently fallen to Bay Area averages since 1985."|
|Page 2, Paragraph 1||"Studies that favor the outcome held by CDHS the association between radiation and melanoma) are summarized, but those papers that do not support that association are critically reviewed or even reanalyzed."||In general, we summarized studies, unless we felt there were aspects of interpretation or design that we disagreed with. This applied primarily to two studies: |
|Dr. Richter cites the Los Alamos studies, which did not find an association between melanoma and radiation.||Although an association was not found in this population (total of 20 cases), this does not rule out an association within the LLNL workforce. Also, the Los Alamos study employed the same matching-on-start-date technique used for the LLNL case-control study, which may again have obscured a potential relationship.|
|Page of comment/ Section of report||Comment||CHDS response|
|Page 13, LLNL Announce... |
|In reference to higher rates of "early stage" cancers other than breast or cervical, it is technically correct that the category of "all other" in situ cancers in women is statistically elevated. The numbers are small. It is rather unusual that this review singles out a category that represents miscellaneous in situ cancers. It is not a particularly meaningful finding or category. There are other much more important and interpretable findings in the cancer incidence report, such as the statistically lower rates of overall invasive cancer in LLNL women, and specifically, lower rates of invasive genital organ cancer in women. The elimination of this reference and possibly the substitution of a more meaningful one is suggested.||This information was drawn from a published news report on the LLNL study that states: "The frequency of early stage cancers other than breast and cervix for lab women was significantly high, though, with 13 cases observed and 5.2 expected." |
We will include the finding regarding "female genital organ cancers."
|This review could also benefit from a reference to the discussion of the comparison between the two case-control studies that appears in the LLNL report (UCRL-LR-106723, Pages 46-49).||We will include a reference to this discussion.|
|Second, the argument that race should have been used as a matching factor is an insignificant issue. Only one control selected under the algorithm was Afro-American, and there were no Asian or Latino controls.||Perhaps this did not change the ultimate results, but the likelihood of an African-American person having melanoma is much lower than among Caucasians, so it is not optimal, especially given that 16,000 possible controls were available. With a small number of cases, and only one control per case, the significance of any single control becomes greater.|
|The additional cases in the 1994 case control study compensates for the use of a single control to maintain the power of the study.||The LLNL study had approximately the same power as the original Austin/Reynolds study, although the Austin/Reynolds study had only half the number of cases. The authors could have greatly increased the study power by including more controls. The costs of the additional controls could have been offset by dropping other parts of the study (such as the computerized word count analysis), and a shorter, standardized questionnaire could have been used, rather than the open-ended interview requiring transcription, which may have been more effective in any case.|
|Page of comment/ Section of report||Comment||CHDS response|
|Letter to CDHS, page 2||We recommend CDHS address these additional points: |
CDHS should recommend there be an independent review of the data, methodology and interpretation of the 1994 LLNL study to validate its findings.
|Although we agree that such a review could be beneficial in elucidating the possible reasons for the negative findings, CHDS is unlikely to undertake this initiative at this point. |
The extensive and costly re-analysis of the RCE study, which was sponsored by the LLNL, represented an unusual degree of scrutiny for studies of this type.
|Page 3||We believe that the study by CDHS "Cancer incidence among children and young adults in Livermore, California: 1960-1991, provisional report, September 6, 1995 also identified elevated levels of brain cancer in children in some, but not all decades studied. |
CDHS should include these findings in the report.
|We will include these findings.|
|Page 3, Page 22 of report, 4th paragraph||You state "In 1984 …Fortunately, as exposure conditions at LLNL have improved over time, it would be anticipated that any risk at that facility has been commensurately reduced." We wondered what is the evidence to support that exposure conditions at LLNL have improved over time? |
CDHS should clearly state that "exposure conditions at LLNL" is an unsupported assumption, or the report should reference the basis of this assumption. We note that even if individual worker's exposures have been reduced over time, if the number of workers at LLNL has increased during this same period, the population dose may be higher than in the past.
|We have revised the document to reference LLNL's assertion that this reduction in exposure has occurred.|
Many of the comments fell in several main areas, so we have written a general response to each area that addresses a number of specific points.
- Methodology of LLNL case control study
- Evidence for melanoma excess vs. surveillance bias/early detection
- Evidence for association between melanoma and radiation:
- within LLNL studies
- within the scientific literature.
1) Methodology of the LLNL case-control study
Matching as a technique to control confounding seems appealing, but has a number of scientific disadvantages. Thesedisadvantages, plus the more recent development of alternative analytical techniques to control confounding, havereduced the desirability of matching. A major limitation of matching is the inability to evaluate the effect of a factorthat has been matched on the risk of the outcome. In the situation of LLNL, if start date is closely associated withexposure, then matching on it prevents the investigation of the effect of exposure on the outcome. The fact that theexposure factors in the Austin/Reynolds study are all temporally related to LLNL activities is actually an argument against using it as a matching factor, rather than a reason for matching on this. This would make it a factor thatshould be investigated and explored.
Although laboratory activities may have changed over time, that does not necessarily introduce a bias. The controlsare not being selected from the "later" employees, but they would be randomly selected from all time periods coveredby case accrual, so there would be no reason for this selection to produce bias. This would allow investigators toevaluate whether activities that were associated with greater exposures (and may also have tended to take placeearlier), were more prevalent than those that occurred later. This cannot be investigated if start date is used as amatch.
[Moreover, if the exposure that caused melanoma stems in part of primarily from contaminant releases to thecommunity that occurred at specific points in time, then matching on start date would over-control for this effect in away that would prevent it from being discovered. For example, if the melanoma were caused by tritium releases tothe community during the late 1960s and 1970s, then this exposure would affect both employees and thecommunity.]
In our view, it seems the "safest" approach is to select a method that allows full exploration of the possible exposuresof interest, and that would mean not matching on start date.
Use of radiation measurements
LLNL of course had access to the radiation data, although there are questions regarding its accuracy. However, actualradiation doses were never directly used in the analysis. Dosimetry records also included recorded doses of ionizingradiation received by employees prior to employment at LLNL. Doses were then coded on a scale of 0-5 and, andstatistical tests were conducted "to remove the effects of skewing" (presumably the distribution of the radiation levelsdid not follow the normal, or "bell" curve). They presumably conducted a non-parametric statistical test, used fornon-normally distributed data. The authors calculated the average dose (based on this categorical scale) for cases vs.controls, finding the two to be similar. They did not describe the distribution of radiation dose levels.
Also, the authors do not include radiation dose in any multivariable analysis, which would allow for simultaneouscontrol of other factors. Although it seems that the cases and controls in this study group are quite comparable interms of their exposures, a multivariable analysis would be necessary to answer this question more accurately.
LLNL comments that "subsequent analysis of the radiation badge data from the 1984 cases did demonstrate recallbias." It is unclear what this statement is based on. However, the Schwartzbaum re-analysis of the data, whichincluded evaluation of the dosimetry data, specifically examined the possibility of whether recall bias accounted forthe findings, finding no evidence of bias.
We contacted the current LLNL Medical Director, Dr. James Seward, to find out what the original algorithm was andhow and why it was changed. Subsequently, Dr. Seward replied that he contacted as many authors of the report aspossible, but none could recall the original algorithm nor why it was changed, but that all persons queried agreed itwas a minor change. Presently, we are unaware if a written record exists documenting any of these decisions.
2) Evidence for melanoma excess vs. surveillance bias/early detection
Melanoma rates were consistently elevated, across different time periods, using different reference groups, andamong males and females. The consistency of this result supports the likelihood that there was a genuine excess ofmelanoma among the LLNL workforce and Livermore community that was not merely an artifact of early detection. (See Tables 3 and 4 of melanoma rates among different study populations and Figure 2, which demonstrates an excess of melanoma compared to expected rates, which is not limited to thinner tumors.)
The articles reviewed offer mixed and qualified evidence, but tend to support a limited role for surveillance bias,rather than the main reason for the excess. The findings are summarized below.
Hiatt 1986: there could be either physician diagnosis bias, or an environmental agent (or agents) responsible.
Hiatt 1993: there could be surveillance bias up to 1976, but data do not support this after that time.
Schneider 1990: thinner tumors at LLNL than a community laboratory, but no difference in the earlier period around 1976.
Schneider 1987: rate of melanoma increased at LLNL increased, as did the proportion of thin tumors; authors also note that a high percentage of in-situ cases is consistent with a high overall incidence.
Gong 1992: excess thin but not thick tumors; promoting the idea that many early-detected melanomas would have spontaneously regressed.
Joint Legislative Audit Committee: high melanoma rate appeared to be correct.
DOE Panel: rate of melanoma appeared to be 3-4 times higher than general population.
LLNL-commissioned panel: early detection was an unlikely explanation for excess, as there was no decrease in later time periods.
Early detection usually would result in more tumors in the immediate time period in which they were detected, butfewer tumors in later time periods, as they would have been discovered and counted while they were thinner.However, there was no decrease in the numbers of tumors detected in subsequent study periods. In order for thissecond hypothesis still to be true, it would mean that the excess number of thin tumors would have disappeared ontheir own. Spontaneous regression is a rare phenomenon, and thus early detection seems unlikely to explain theexcess.
[Even if surveillance bias were a reason for the elevation among LLNL workers, that would be unlikely to explainthe excess melanoma which was seen among children and young adults in the Livermore community for the threedecades from 1960-1990.]
3a) Evidence for association between melanoma and radiation at LLNL
Our findings that melanoma may be associated with LLNL-related exposures such as ionizing radiation are well-supported by the studies of LLNL.
The association between occupational risk factors and melanoma is based on many analyses, in many models. Riskratios varied, with most showing statistical significance:
- work with ionizing radiation: Odds Ration (OR) = 3.7 (95% CI = 1.6 - 8.6) (50);
- radioactive materials (ever vs. never exposed): OR = 2.8 (1.1-7.1) (50);
- radiation-occupations: summary OR = 10.8 (95% CI: 1.4-85.1) (52).
Schwartzbaum et al recalculated the odds ratio estimates for reported employment in proximity to radiation for 588models containing different sets of confounding variables, finding the odds ratios ranged from 3.0 to 46.4 (allstatistically significant). The median odds ratio and odds ratio adjusted for basic confounders were both 5.4.
Furthermore, the Schwartzbaum paper was based on an extensive review and re-analysis of the data that specificallyattempted to determine whether there were sources of error or bias that could have falsely led to the associationbetween radiation exposure and melanoma. They concluded: "No definitive evidence for influential matched sets,confounding, recall bias, or any other sources of bias was detected. These results suggest that the odds ratio forreported employment in proximity to radiation may be valid."
3b) Evidence for association between melanoma and ionizing radiation in the scientific literature and biological plausibility
Most cancers can be caused by ionizing radiation. The body of epidemiology between ionizing radiation andmelanoma is mixed, but there continues to be new data supporting a possible link between radiation and melanoma.We support a careful and specific investigation of this potential association, including development of new studiesthat are better designed to address this question, as well as consideration of what previous studies have had null findings and which have had positive findings, and why they may differ.(Biological plausibility and specific exposure pathways in the Livermore community are further addressed in thereport.)
The relative rareness of melanoma may have hindered its identification as a radiation-related cancer. In 2002,approximately 900,000 Americans were diagnosed with basal cell skin cancer, another 300,000 with squamous cellskin cancer, but only 53,000 with melanoma (26). Studies finding a small increase in skin cancersmay not be able to detect an increase in melanoma specifically. Because of this, fairly large study populations will berequired to investigate this issue adequately.
Some cancers will be caused more easily by radiation than others. Also, some cancers have a high natural incidencebut low relative risks per radiation dose (e.g., colon); some have a low natural incidence but a high relative risk perradiation dose (e.g., thyroid); and other cancers of high natural incidence also have a high relative risk per radiationdose (e.g., breast). Thus, it is possible that melanoma could be caused by ionizing radiation, but perhaps it was notnoted originally because it may not be as radiosensitive as other cancers.
In addition to the issue of melanoma's relative rareness (and probably often as a result of this), studies of nuclearworkers have often combined melanoma and non-melanoma, limiting the available information on melanomaspecifically. Studies with negative results could be partly due to the healthy worker effect (persons who work tend tobe healthier than the general population). However, it may be that more sensitive tests such as dose-response trendtests are required to detect a relationship between melanoma and ionizing radiation. For example, a large study ofnuclear workers was cited as negative for a relationship between melanoma and radiation in a reference book oncancer (64), but a more sensitive analysis found a dose-response relationship of 1.5 excess relative risk per Sievert ofexposure for mortality from skin cancer (types combined).
Also, studies of survivors of the atomic bomb in Japan have generally been seen as supporting a relationship onlybetween radiation and non-melanoma skin cancer. However, Japanese have a lower baseline risk for melanomabecause of their skin type, and it is possible that an association exists that was not detected originally. A recent articleby the NCI states that the excess relative risk point-estimates for melanoma were large but statistically non-significant, as the number of cases was small (n=10) (65). As mentioned earlier, because melanoma is much lesscommon than basal and squamous cell cancers, it would be predicted that melanoma would be found much lessfrequently. Detecting a less common event is more difficult statistically.
The data in BEIR V are consistent with this interpretation (32). The BEIR V reports that skincancers were among the first cancers to be recognized as radiation-induced. In general, however, the studies cited donot provide enough information on melanoma separately to evaluate it. One of three studies cited found excess skincancer, in a combination of six basal cell carcinomas and two melanomas. Another noted excess skin cancer, reportedto be primarily basal cell carcinomas. Thus although there may have been fewer melanomas in absolute numbers, because melanoma incidence was not provided separately (probably due to fewcases), it cannot be ruled out that melanoma incidence is not also increased along with other skin cancers.
Some relevant evidence has been noted in the following studies. Larger studies appear more likely to detect an effect.
Occupational ionizing radiation exposure:
- Cohort of 191,333 Canadian radiation workers; statistically significant elevations (66);
- Cohort of 68,588 American radiologic technologists; Relative Risk (RR)=1.8 (95% CI = 0.6 - 5.5); among those who worked for five or more years before 1950, RR = 2.4 (95% CI = 0.7-8.7) (67);
- British radiologists (1897-1979); elevated in some periods, but not statistically significant (68);
- Occupational exposure, significant elevation (24); and
- Chemists exposed to ionizing radiation, significant elevation (69).
Pilots and flight attendants (gamma ray exposure):
- Meta-analysis of cancer incidence and flight personnel; statistically significant (RR=1.97) (70);
- Elevated, statistically significant (71);
- Elevated, near statistical significance (72);
- Elevated, not statistically significant (73); and
- Elevated, near statistically significance (74).
- Review article stating evidence for increased risk for cancers other than lung from radon exposure, including melanoma (75);
- Radon levels correlated with melanoma in southwest England; statistically significant correlation (76); and
- Melanoma significantly correlated with radon exposure in home (77).
Ionizing radiation means that radioactive particles and rays encounter materials and carry enough energy that theystrip away electrons from atoms and molecules that normally are electrically balanced (10). Thestripped atom or molecule becomes an ion, and ions formed in living tissue by external causes can be hazardous tothat tissue's health (10). The main types of ionizing radiation are alpha, beta, and gamma. Alpharays are charged particles that have a lot of energy of motion, but do not have as much penetrating power as othertypes of radiation (10). Alpha particles deposit their energy in a small volume; in biological tissue,the range is approximately 25-80 um (micrometers) (10). Studies of diffusion of plutonium-239through the various skin layers found that most of the radioactivity was found in the epidermis (about 2-4%penetrated as far as the deeper dermal layer) (35). Once inside the human body, an alpha particle canbe much more damaging to tissue than beta or gamma radiation (10). Plutonium is an alpha emitter(plutonium-239 also emits gamma rays). Radioactive materials can also emit beta particles, which are high-energyelectrons. Beta rays (these are also particles) are lighter and more penetrating than alpha particles. Gamma rays are atype of light (energy), not a particle. They travel at the speed of light, have no mass but tremendous penetratingpower, and can pass through the body. Nuclear explosions are a source of gamma rays.
Tritium is a beta emitter. It is a radioactive isotope of hydrogen, and, once released to the atmosphere, it can be takenup by all hydrogen-containing molecules and distributed widely through the environment (78). In the air, it binds withoxygen to form radioactive water molecules, forming tritiated water. Tritiated water or vapor may readily beabsorbed into the body through the skin, inhalation, or ingestion (10,34). Contactbetween skin and surfaces contaminated with tritium can result in transfer of tritium to cells within the skin (79,80).For example, wearers of watches with tritium as a permanent light source on watch dials had increased tritium skindoses and increased levels of excreted tritium in urine (79). An investigation of tritium levels amongresidents near a heavy water (tritium) reactor facility found comparable tritium levels in urine to tritium levels inprecipitation near these locations (81), indicating how tritium disperses through water inside and outside the body.
Frequency of Cancer
Although incidence of and mortality from many cancers have been decreasing in California, cancer overall is still thesecond leading cause of death (13). According to current rates, one of every two men and two ofevery five women will develop some form of cancer in their lifetimes (13). The older someonebecomes, the more likely it is that he or she will eventually get cancer. Breast cancer is the most common canceramong women, and prostate cancer is the most common cancer among men.
Lung cancer is the second most common cancer for both men and women (13). According to currentrates, 1 of 12 men will develop lung cancer, but this risk is 10 to 20 times higher among smokers. It is estimated that85% of lung cancer is caused by cigarette smoking (not including exposure to smoke from others).
Causes of Cancer
When and where cancer occurs depends partly on chance. Information is, however, available about how cancerdevelops. Cancer is a slow process, generally requiring years or even decades. The process of cancer can be startedby a causative agent, which might be one factor among many. These agents could include radiation(28), chemical exposures (82,83), viruses (84), or possibly bacteria (85,86). But there must also be apathway by which this agent can reach someone. This could be through the air, through water or food, or throughsexual transmission. Additionally, the agent has to exert an effect that causes a biological change in the person'sbody. The exposure must also last long enough for harm to occur.
There are many different types of cancers, and different cancers have different causes. For example, in the body thereare natural hormones that play a role in whether someone gets cancer (87,88). For example, breast cancer is related tohormonal functions such as early onset of menstruation and when a woman bears children(89,87,88). Exposure to sunlight is a factor in skin cancer (90). Drinking alcohol canbe the cause of some cancers, such as liver cancer (91). Some cancers are caused by viruses (84); cervical cancer is primarily caused by a virus that is sexually transmitted(48). Cancer does not generally result from one exposure or influence (92). Instead, there are usually several factors that work together to cause cancer.
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(1) Lawrence Livermore National Laboratory. Final environmental impact statement and environmental impact report for the continued operation of Lawrence Livermore National Laboratory and Sandia National Laboratory. Livermore, California: Lawrence Livermore National Laboratory; 1992 Aug.
(2) United States Environmental Protection Agency (USEPA). Confirmatory sampling of plutonium in soil from the southeast quadrant of the Lawrence Livermore National Laboratory. National Air and Radiation Environmental Laboratory, USEPA. 1994 Aug 15.
(3) Moore DH, Patterson HW, Hatch F, Discher D, Schneider JS, Bennett D, Mendelsohn ML. Case-control study of malignant melanoma among employees of the Lawrence Livermore National Laboratory. Am J Ind Med 1997;32:377-91.
(4) Agency for Toxic Substances and Disease Registry. Plutonium contamination in Big Trees Park, Lawrence Livermore National Laboratory health consultation, Alameda County, Livermore, California. Atlanta: US Department of Health and Human Services; 1999 May 17.
(5) Agency for Toxic Substances and Disease Registry. Public Health Assessment: Lawrence Livermore National Laboratory: Plutonium 239 sewage sludge used as a soil amendment in the Livermore community. Atlanta: US Department of Health and Human Services, 2003 April 29.
(6) California Department of Health Services. Report: Proposed process to address the historic distribution of sewage sludge containing plutonium released from the Lawrence Livermore National Laboratory. Oakland, CA: California Department of Health Services, November 2002.
(7) Agency for Toxic Substances and Disease Registry. Health Consultation: Lawrence Livermore National Laboratory, Main Site; Lawrence Livermore National Laboratory (Site 300); Savannah River Site: Tritium releases and potential offsite exposures. Atlanta: US Department of Health and Human Services, 2002 March 11.
(8) Weisman J. Alarm over radioactive rainwater; lab surprised at tritium levels. The Tri-Valley Herald; 1994 Mar 25.
(9) Agency for Toxic Substances and Disease Registry. Public Health Assessment: Lawrence Livermore National Laboratory: Community exposures to the 1965 and 1970 accidental tritium releases. Atlanta: US Department of Health and Human Services, 2002 August 7.
(10) Agency for Toxic Substances and Disease Registry. Toxicological profile for ionizing radiation. Atlanta: US Department of Health and Human Services; 1999 Sep.
(11) United States Environmental Protection Agency. Radiation protection. Date accessed: August 19, 2003. USEPA. http://www.epa.gov/radiation/index.html.
(12) Agency for Toxic Substances and Disease Registry. Health consultation: Lawrence Livermore National Laboratory: community health concerns, Alameda County, Livermore, California. Atlanta: US Department of Health and Human Services, 2003 April 25.
(13) Perkins CI, Cohen R, Morris CR, Allen M, Kwong SL, Schlag R, et al. Cancer in California: 1988-1995. Sacramento, CA: California Department of Health Services, Cancer Surveillance Section; April, 1998.
(14) Java J. Rare cancer probe to include valley. The Tri-Valley Herald; 1978 Feb 2.
(15) Lawrence Livermore National Laboratory. Melanoma at LLNL: an update. Energy and Technology Review. University of California, Lawrence Livermore National Laboratory; 1994 Mar; UCRL-52000-94-3.
(16) Hall HI, Miller DR, Rogers JD, Bewerse B. Update on the incidence and mortality from melanoma in the United States. J Am Acad Dermatol 1999;40:35-42.
(17) Rigel DS, Friedman RJ, Kopf AW. The incidence of malignant melanoma in the United States: issues as we approach the 21st century. J Am Acad Dermatol 1996;34:839-47.
(18) Loria D, Matos E. Risk factors for cutaneous melanoma: a case-control study in Argentina. Int J Dermatol 2001;40:108-14.
(19) Elwood JM, Jopson J. Melanoma and sun exposure: an overview of published studies. Int J Cancer 1997;73:198-203.
(20) Tenkate TD. Occupational exposure to ultraviolet radiation: a health risk assessment. Rev Environ Health 1999;14:187-209.
(21) Hemminki K, Jiang Y, Steineck G. Skin cancer and non-Hodgkin's lymphoma as secondmalignancies. markers of impaired immune function? Eur J Cancer 2003 Jan;39:223-9.
(22) Mithoefer AB, Supran S, Freeman RB. Risk factors associated with the development of skin cancer after liver transplantation. Liver Transpl. 2002 Oct;8:939-44.
(23) Elwood JM, Whitehead SM, Davison J, Stewart M, Galt M. Malignant melanoma in England: risks associated with naevi, freckles, social class, hair color, and sunburn. Int J Epidemiol 1990;19:801-10.
(24) Pion IA, Darrell SR, Garfinkel L, Silverman MK, Kopf AW. Occupation and the risk of malignant melanoma. Cancer 1995;75 (Supplement January 15, 1995):637-644.
(25) Austin DF, Reynolds P. Occupation and malignant melanoma of the skin. In: Recent results in cancer research. Vol. 102. Berlin: Springer-Verlag, 1986;98-107.
(26) Geller AC, Annas GD. Epidemiology of melanoma and non-melanoma skin cancer. Seminars in Oncology Nursing 2003;19:2-11.
(27) Koh HK. Cutaneous melanoma. N Eng J Med 1991;325:171-82.
(28) Boice JD Jr., Land CE, Preston DL. Ionizing radiation. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 319-54.
(29) Shimizu Y, Kato H, Schull WJ. Studies of the mortality of A-bomb survivors: 9. Mortality, 1950-1985: Part 2. Cancer mortality based on the recently revised doses (DS86). Radiat Res 1990;121:120-141.
(30) Beral V, Fraser P, Carpenter L, Booth M, Brown A, Rose G. Mortality of employees of the atomic weapons establishment, 1951-82. BMJ 1988;297:757-70.
(31) Checkoway H, Pearce N, Crawford-Brown DJ, Cragle DL. Radiation doses and cause-specific mortality among workers at a nuclear materials fabrication plant. Am J Epidemiol 1988;127:255-66.
(32) Committee on the Biological Effects of Ionizing Radiations, Board on Radiation Effects Research, National Research Council. Health effects of exposure to low-levels of ionizing radiation, BEIR V. Washington, DC: National Academy Press, 1990.
(33) Boice JD. Cancer following medical irradiation. Cancer 1981;1081-1090.
(34) Okada S, Momoshima N. Overview of tritium: characteristics, sources, and problems. Health Phys 1993;65:595-609.
(35) Tymen H, Gerasimo P, Hoffschir D. Contamination and decontamination of a rat and human skin with plutonium and uranium, studied with a Franz's chamber. Int J Radiat Biol 2000;76:1417-24.
(36) Hennekens CH, Buring JE. Epidemiology in medicine. 1st ed. Boston/Toronto: Little, Brown and Company, 1986.
(37) Austin DF. A study of cancer incidence in Lawrence Livermore Laboratory employees, report no. 1, malignant melanoma. Sacramento, California: California Department of Health Services, Resource for Cancer Epidemiology Section; 1980.
(38) Austin DF, Reynolds PJ, Snyder MA, Biggs MW, Stubbs HA. Malignant melanoma amongemployees of Lawrence Livermore National Laboratory. Lancet 1981;2:712-6.
(39) Reynolds P, Austin DF. Cancer incidence among employees of the Lawrence Livermore National Laboratory: 1969-1980. West J Med 1985;142:214-8.
(40) Hiatt RA, Fireman B. The possible effect of increased surveillance on the incidence of malignant melanoma. Prev Med 1986;15:652-60.
(41) Schneider JS, Sagebiel RW, Moore DH, Lawton GM. Melanoma surveillance and earlier diagnosis. Lancet 1987;1:1435.
(42) Schneider JS, Moore DH, Sagebiel RW. Early diagnosis of cutaneous malignant melanoma at Lawrence Livermore National Laboratory. Arch Dermatol 1990;126:767-9.
(43) Gong G, Whittemore AS, West D, Moore DH II. Cutaneous melanoma at Lawrence Livermore National Laboratory: comparison with rates in two San Francisco Bay Area counties. Cancer Causes Control;1992;3:191-7.
(44) King M, Spooner D, Rowlands DC. Spontaneous regression of metastic malignant melanoma of the parotid gland and neck lymph notes: a case report and review of the literature. Clin Oncol (R Coll Radiol) 2001;13:466-9.
(45) Hiatt RA, Krieger N, Sagebiel RW, Clark WH Jr., Mihm MC Jr. Surveillance bias and the excess risk of malignant melanoma among employees of the Lawrence Livermore National Laboratory. Epidemiol 1993;4:43-7.
(46) Roberts G Jr. Lab workers during 1974-1997 have high rate of cancer. Tri-Valley Herald; 2001 Nov 15.
(47) Widener A. Lab's cancer rates below norm: but of 17,785 workers in new study, men had higher levels of two types. Contra Costa Times; 2001 Nov 15.
(48) Schiffman MH, Brinton LA, Devesa SS, Fraumeni JF Jr. Cervical cancer. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 1090-1116.
(49) Austin DF, Reynolds P. A case-control study of malignant melanoma among Lawrence Livermore National Laboratory employees. Sacramento, California: California Department of Health Services, Resource for Cancer Epidemiology Section; 1984 July 3; Report No. 3.
(50) Austin DF, Reynolds P. Investigation of an excess of melanoma among employees of the Lawrence Livermore National Laboratory. Am J Epidemiol 1997;145:423-31.
(51) Moore DH, Patterson HW, Hatch F, Discher D, Schneider JS, Bennett D. Workplace investigation of increased diagnosis of malignant melanoma among employees of Lawrence Livermore National Laboratory. Livermore, California: Lawrence Livermore National Laboratory, University of California; 1994 Aug; report no.: UCRL-LR-106723.
(52) Schwartzbaum JA, Setzer RW, Kupper LL. An exploratory analysis of the occupational correlates of large pigmented nevi at Lawrence Livermore National Laboratory. J Occup Med 1990;32:605-11.
(53) Morton RF, Hebel JR, McCarter RJ. A study guide to epidemiology and biostatistics. Gaithersburg (MD): Aspen Publishers Inc., 1996.
(54) Joint Legislative Audit Committee. The cancer incidence among workers at Lawrence Livermore Laboratory: a synthesis of expert reviews of the study. Sacramento, California: California Legislature, Joint Legislative Audit Committee; 1980 May 23.
(55) Upton AC, Burr WW, Lee JAH, Long JE, Urbach F, Zelen M. Report on the Ad Hoc Advisory Board on melanoma. Arlington, Virginia: American Institute of Biological Sciences, Ad Hoc Advisory Board on Melanoma; July 1980. US Department of Commerce, National Technical Information Service Report No. DE82018384.
(56) Shy CM, Checkoway H, Marshall EG. Malignant melanoma at a scientific laboratory: a synthesis of reviewer's comments on the Austin and Reynolds' study of employees at the Lawrence Livermore National Laboratory. Chapel Hill, North Carolina: University of North Carolina, School of Public Health, Department of Epidemiology, Occupational Health Studies Program; 1985 Nov 15. Report No. UCRL--15737.
(57) Kupper LL, Setzer RW, Schwartzbaum J, Janis J. A case-control study of malignant melanoma among Lawrence Livermore National Laboratory employees: a critical review. Chapel Hill, North Carolina: The Livermore Melanoma Project Partnership; 1987 Jul 1.
(58) Schwartzbaum JA, Setzer W, Kupper LL. Exposure to ionizing radiation and risk of cutaneous malignant melanoma: search for error and bias. Ann Epidemiol 1994;4:487-96.
(59) Gardner MJ. Father's occupational exposure to radiation and the raised level of childhood leukemia near the Sellafield nuclear plant. Environ Health Perspect Aug 1991;94:5-7.
(60) California Department of Health Services, Environmental Health Investigations Branch. Cancer incidence among children and young adults in Livermore, California: 1960-1991, provisional report. 1995 Sep 6.
(61) California Cancer Registry, California Department of Health Services. Cancer incidence in California: 1988-1993. Sacramento (CA): California Department of Health Services. 1996.
(62) Harris JA. Birth defects around Livermore: 1983-1989. Sacramento (CA): California Department of Health Services, California Birth Defects Monitoring Program; 1996 Mar 15.
(63) California Department of Health Services. Proposed process to address the historic distribution of sewage sludge containing plutonium released from the Lawrence Livermore National Laboratory. Oakland (CA): California Department of Health Services; 2002 Nov.
(64) Armstrong BK, English DR. Cutaneous malignant melanoma. Ionizing radiation. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer Epidemiology and Prevention. 2nd ed. Oxford: Oxford University Press, 1996:1282-1312.
(65) Ron E, Preston DL, Kishikawa M, Kobuke T, Iseki M, Tokuoka S, et al. Skin tumor risk among atomic-bomb survivors in Japan. Cancer Causes Control 1998;9:393-401.
(66) Sont WM, Zielinski JM, Ashmore JP, Jiang H, Krewski D, Fair ME, Band PR, Letourneau EG. First analysis of cancer incidence and occupational radiation exposure based on the National Dose Registry of Canada. Am J Epidemiol 2001;153:309-18.
(67) Freedman DM, Sigurdson A, Rao RS, Hauptmann M, Alexander B, Mohan A, Morin Doody M, Linet MS. Risk of melanoma among radiologic technologists in the United States. Int J Cancer 2003;103:556-562.
(68) Berrington One hundred years of observation of British radiologists: mortality from cancer and other causes 1897-1997. Br J Radiol 2001;74:507-19.
(69) Wright WE, Peters JM, Mack TM. Organic chemicals and malignant melanoma. Am J Ind Med 1983;4:577-81.
(70) Ballard T, Lagorio S, De Angelis G, Verdecchia A. Cancer incidence and mortality among flight personnel: a meta-analysis. Aviat Space Environ Med 2000;71;216-24.
(71) Irvine D, Davies DM. The mortality of British Airways pilots, 1966-1989: a proportional mortality study. Aviat Space Environ Med 1992;63:276-9.
(72) Goodman KJ, Bible ML, London S, Mack TM. Proportional melanoma incidence and occupation among White males in Los Angeles County (California, United States). Cancer Causes Control 1995;6:451-9.
(73) Pukkala E, Auvinen A, Wahlberg G. Incidence of cancer among Finnish airline cabin attendants, 1967-92. BMJ 1995;311:649-52.
(74) Vagero D, Swerdlow AJ, Beral V. Occupation and malignant melanoma: a study based on cancer registration data in England and Wales and in Sweden. Br J Ind Med 1990;46:317-24.
(75) Axelson O. Cancer risks from exposure to radon in homes. Environ Health Perspect 1995;103 Suppl 2:37-43.
(76) Etherington DJ, Pheby DFH, Bray FI. An ecological study of cancer incidence and radon levels in south west England. Eur J Cancer 1996;32A;1189-1197.
(77) Henshaw DL, Eatough JP, Richardson RB. Radon as a causative factor in induction of myeloid leukaemia and other cancers. The Lancet 1990;335:1008-12.
(78) Etnier EL, Travis CC, Hetrick DM. Metabolism of organically bound tritium in man. Radiat Res 1984;100:487-502.
(79) Brunner P, Schneider P, Scheicher H, Seyerl G, Kurnik P, Ennemoser O, et al. Tritium intake by exposure to plastic case watches. Health Phys 1996;70:484-7.
(80) Johnson JR, Dunford DW. Dosimetric models of 3H from skin absorption following contact with T2-contaminated surfaces. Health Phys 1985;48:110-3.
(81) Kotzer T, Trivedi A. Dosimetric implications of atmospheric dispersal of tritium near a heavy-water research reactor facility. Radiat Prot Dosimetry 2001;93:61-6.
(82) Linet MS, Cartwright RA. The leukemias. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 841-92.
(83) Monson RR. Occupation. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 373-405.
(84) Mueller NE, Evans AS, London WT. Viruses. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 502-31.
(85) Nomura A. Stomach cancer. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 707-24.
(86) Brenner H, Arndt V, Bode G, Stegmaier C, Ziegler H, Stumer T. Risk of gastric cancer among smokers infected with Helicobacter Pylori. Int J Cancer 2002;98:446-9.
(87) Bernstein L, Henderson BE. Exogenous hormones. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 462-488.
(88) Henderson BE, Pike MC, Bernstein L, Ross RK. Breast cancer. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p.1022-39.
(89) California Cancer Registry. Monitoring Cancer in California. Date accessed: December 3, 2002. California Cancer Registry, Cancer Surveillance Section, Department of Health Services. Sacramento, CA. http://www.ccrcal.org/brochure/monitor.pdf.
(90) Armstrong BK, English DR. Cutaneous malignant melanoma. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 1313-30.
(91) Jensen OM, Paine SL, McMichael AJ, Ewertz M. Alcohol. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer Epidemiology and Prevention. 2nd ed. Oxford: Oxford University Press, 1996:290-318.
(92) Rothman KJ, Poole C. Causation and causal inference. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. Oxford: Oxford University Press; 1996. p. 3-10.